WO2025175221A1

WO2025175221A1 - Fluid pressure oscillator driven dynamic pressure aspiration device

Info

Publication number: WO2025175221A1
Application number: PCT/US2025/016107
Authority: WO
Inventors: Halil Karabey; Han-Wei Wang; Stephen Porter
Original assignee: Stryker European Operations Ltd; Stryker Corp
Current assignee: Stryker European Operations Ltd; Stryker Corp
Priority date: 2024-02-16
Filing date: 2025-02-14
Publication date: 2025-08-21
Anticipated expiration: 2026-08-16

Abstract

An aspiration modulation device for use with an aspiration catheter and a vacuum source. The aspiration modulation device comprises a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber. The aspiration modulation device further comprises a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating a vacuum pressure within the pressure chamber.

Description

FLUID PRESSURE OSCILLATOR DRIVEN DYNAMIC PRESSURE ASPIRATION DEVICE

FIELD OF THE INVENTION

[01] The present disclosure relates generally to medical devices and intravascular medical procedures, and more particularly, to devices and methods for aspirating objects from the anatomy, e.g., a clot from the vasculature of the patient.

BACKGROUND OF THE INVENTION

[02] It is often desirable to remove tissue from the body in a minimally invasive manner as possible, so as not to damage other tissues. For example, removal of tissue from within a vasculature, such as blood clots, may improve patient conditions and quality of life.

[03] Many vascular system problems stem from insufficient blood flow through blood vessels. One cause of insufficient or irregular blood flow is a blockage within a blood vessel referred to as a blood clot or thrombus, which may embolize and form an embolus in a patient vasculature. Thrombi can occur for many reasons, including damage to the arterial wall from atherosclerotic disease, trauma caused by surgery, or due to other causes. When a thrombus forms, it may effectively stop the flow of blood through the zone of formation. Sometimes such thrombi are harmlessly dissolved in the blood stream. At other times, however, such thrombi may lodge in a blood vessel where they can partially or completely occlude the flow of blood. If the partially or completely occluded vessel feeds blood to sensitive tissue, such as the brain, lungs or heart, for example, serious tissue damage may result.

[04] For example, thrombosis of one of the carotid arteries can lead to an arterial ischemic stroke (AIS) due to insufficient oxygen supply to vital regions in the brain. As another example, if one of the coronary arteries is 100% thrombosed, the flow of blood is stopped in that artery, resulting in a shortage of oxygen carrying red blood cells, e.g., to supply the muscle (myocardium) of the heart wall. Oxygen deficiency reduces or prohibits muscular activity, can cause chest pain (angina pectoris), and can lead to death of myocardium, which permanently disables the heart to some extent. If the myocardial cell death is extensive, the heart will be unable to pump sufficient blood to supply the body's life sustaining needs. Indeed, a large percentage of the more than 1.2 million heart attacks in the United States are caused by blood clots (thrombi) that form within a coronary artery. As still another example, clots in the peripheral vasculature may result in amputation of a limb.

[05] When symptoms of an occlusion are apparent, immediate action should be taken to reduce or eliminate resultant tissue damage. Indeed, clinical data indicates that clot removal may be beneficial or even necessary to improve outcomes. The ultimate goal of any modality to treat these conditions of the arterial or venous system is to remove the blockage or restore patency, quickly, safely, and cost effectively. One approach is to treat a patient with clot dissolving drugs. These drugs, however, do not immediately dissolve the clot from the patient, and are typically ineffective after a predefined window, usually at 2-3 hours after the symptoms arise from the clot. Other approaches involve thrombectomy, i.e., the removal of the clot by aspiration, mechanical retrieval, or a combination thereof. Mechanical retrieval usually involves a deployable mesh-like grid, such as a stent retriever, and is often complicated and dangerous to perform.

[06] Aspiration thrombectomy is generally an effective and common treatment for removing a clot from a blood vessel, especially in the case of AIS. In a typical endovascular aspiration thrombectomy procedure, a catheter is introduced into the vasculature of the patient until the distal end of a catheter is just proximal to the clot, and a vacuum is applied at the proximal end of the catheter, resulting in the ingestion and subsequent removal of at least a portion of the clot into the catheter. Most aspiration systems are susceptible to tip clogging when the clot that is being aspirated is too large for the aspiration conduit at the distal end of the catheter. Current technology for endovascular thrombectomy in ischemic stroke utilizes static loading. Once tip clogging occurs, the pressure in the system precipitously drops to a level that often results in boiling or cavitation of the aspirate within the system. As a result, water vapor is introduced into the system, thereby decreasing the efficiency of the aspiration, and in turn, making it more difficult, if not impossible, to ingest the clot into the catheter. [07] Current trends towards enhancement of aspiration efficacy have seen a few technological advancements. In one approach, catheters with larger inner diameters may be used to facilitate clot evacuation by allowing potentially greater clot pulling forces due to increased suction area and/or by reduced resistance to thrombus passage into the larger lumen of the catheter. However, the use of such large diameter catheters is limited in that they cannot reach clots located in the relatively small diameter vessels of the vasculature of the patient. [08] Another approach uses “cyclic aspiration” to dynamically load the suction pressure during aspiration in various manners to disrupt the structure of the clot and lessen the resistance to ingestion of a given aspiration catheter, thus improving efficiency, and allowing use of potentially smaller, more trackable, catheters to achieve the same or better outcomes than less trackable larger catheters.

[09] One system for dynamically loading the suction pressure employs a cyclically activated valve or similar configuration to achieve the pressure pulsing by blocking main stream flow. Typically, this is done by hand, or via an electro-mechanical or pneumatic valve that blocks aspirate flow from an attached aspiration catheter to the pump for a specified time interval. In some instances, pressure sensing feedback has been suggested as a means for determining when to activate the valve. One cyclical loading method, described in Simon S, Grey CP, Massenzo T, et al., “Exploring the efficacy of cyclic vs static aspiration in a cerebral thrombectomy model: an initial proof of concept study,” Journal of Neurolnterventional Surgery 2014;6:677- 683 and PCT Publication WO2014151209A8, employs a venting mechanism that is automatically placed in an oscillatory pulse mode in response to the application of vacuum to the attached aspiration catheter.

[10] Another system for dynamically loading the suction pressure, described in U.S. Patent Nos. 11 ,547,426 and 11 ,337,712, comprises a vacuum source and a pressurized source of fluid individually connected via valves to a manifold that is fluidly coupled to an attached aspiration catheter. For example, as illustrated in Fig. 1 , a cyclic aspiration system 1 generally comprises a vacuum source (e.g., a vacuum pump) 2, a pressurized source (e.g., a saline bag) 3, and a pressure manifold 4 fluidly coupling the vacuum source 2 and pressurized source 3 to the aspiration lumen (not shown) of an aspiration catheter 5. The cyclic aspiration system 1 further comprises an electronically triggered vacuum valve 6 fluidly coupled between the vacuum source 2 and the pressure manifold 4, an electronically triggered vent valve 7 fluidly coupled between the pressurized source 3 and the pressure manifold 4, and a valve controller 8 that electronically triggers the vacuum valve 6 and vent valve 7 to open and close in any one of a variety of ways to pulse the pressure, within the pressure manifold 4, and thus move the fluid column within the attached aspiration catheter 5. The cyclic aspiration system 1 utilizes the pressure differential between the vacuum source 2 and the pressurized source 3, along with precision operation of electronically, mechanically, or pneumatically triggered valves 6, 7 to rapidly pressurize (bleed in fluid) and depressurize (expose to vacuum) the pressure manifold 4. The cyclic aspiration system 1 may further comprise a vacuum pressure gauge 9 coupled between the vacuum source 2 and the pressure manifold 4, and a main pressure gauge 10 coupled between the pressure manifold 4 and the aspiration catheter 5 for measuring pressures at the input of the manifold (on the vacuum source side) and the output of the manifold (on the aspiration catheter side). The cyclic aspiration system 1 may further comprise a pressure monitoring and operational unit 11 that monitors the fluid pressure measured by the pressure gauges 9, 10 and adjusts the timing and behavior of the valves 6, 7 via the valve controller 8 to modify the overall performance of the aspiration system 1 .

[11] In one example, as illustrated in Fig. 2, the cyclic aspiration system 1 may generate a pressure waveform 12 by essentially pulsing the pressure within pressure manifold 4 between a baseline vacuum pressure of the vacuum source 2 and a vent pressure of the pressurized source 3. In particular, when the vacuum valve 6 is open while the vent valve 7 is closed, the magnitude of the pressure waveform 12 rapidly drops to the baseline vacuum pressure, and then, upon closing the vacuum valve 6 and opening the vent valve 7, the magnitude of the pressure waveform 12 rapidly increases past the vent pressure, and then settles to the vent pressure. The vent valve 7 is then closed while the vacuum valve 6 is still closed, such that the magnitude of the pressure waveform 12 remains at the vent pressure. This sequence is then repeated multiple times to repeatedly decrease and increase the magnitude of the pressure waveform 12 between the baseline vacuum pressure and the vent pressure.

[12] Valve-based systems, such as the cyclic aspiration system 1 of Fig. 1 , are somewhat limited in their ability to precisely generate desired pressure waveforms, as the time resolved pressure within the manifold is dependent on numerous fixed parameters, such as, e.g., the volume, shape, resistance, and compliance of the spaces and connections within the manifold; the configuration, orifice size, resistances and opening time of the valves; on the lag of the electronics system used to sense pressure and control the valves; the length and resistances of the connections and valving to the vacuum and vent base pressures of the vacuum and vent fluid; and the inner diameter (ID), length, and compliance of the aspiration catheter, high quantity of saline used to maximize aspiration effectiveness, etc.

[13] While the pressure extremes of a pressure waveform generated by these valve-based systems may be regulated by various means, such as adjusting valve settings to the base pressures of the vacuum and vent sources, it is much more difficult to alter the shape of the pressure waveform. In particular, flow resistances within the system can limit the rate of flid exchange (i.e., between pressurized and vacuum lines), thus limiting the rate of pressure change. Furthermore, compliances within the fluidic tubing connections and the aspiration catheter can introduce secondary pressure oscillations. These behaviors can be optimized for a given set of operational parameters by altering the system hardware design and material choices, but changing them on-the-fly while the system is in use would be difficult to achieve. For example, in electronically controlled flow systems, solenoid-based valves are extensively used; however, they cannot be controlled beyond the basic opening and closing functions to alter the shape of the pressure and vacuum profiles. Even if feedback is employed, it is difficult to predict the pressure at the distal end of the aspiration catheter without fully understanding all of the aforementioned parameters, as well as changing environmental conditions, including a change in altitude.

[14] Notably, the shape of the pressure waveform generated at the distal end of the aspiration catheter, and in particular, the rate of change of the pressures and their frequencies are related to the degree of pressure effects imparted on the target thrombus, and thus can have a considerable influence on the efficacy of a dynamic pressure aspiration system. Therefore, having greater control over the shape of the pressure waveform at the distal end of the aspiration catheter would potentially have significant impact on the ability to optimize an enhanced aspiration system. However, because valve-based systems are somewhat limited in their ability to precisely generate pressure waveforms, their ability to effectively aspirate thrombi is degraded.

[15] Furthermore, to generate pressure waveforms that vary between the vent pressure and the baseline vacuum pressure (as illustrated in Fig. 2), these valvebased systems require a vacuum source that supplies a relatively high baseline vacuum (very low absolute baseline pressure). Such vacuum sources must exhibit high performance, and are thus, more costly. Furthermore, due to the relatively high baseline vacuum required by these valve-based systems, a substantial amount of blood may be lost and/or vessel collapse may occur when a clot is not being actively ingested by the aspiration catheter. Furthermore, these valve-based systems require a constant source of saline to increase the level of the pressure waveform (i.e., pressurize the system) when the vent valve is open. All of the saline that flows from the source ends up, along with any tissue (e.g., blood or thrombus) aspirated from the patient, in an aspirate collection container, which must be replaced once full. Furthermore, although it is desirable to determine the nature and amount of tissue collected from the patient (e.g., to confirm that the thrombus has been removed from the patient and to ensure that an excessive amount of blood is not being removed from the patient), such determination may be difficult to make given the amount of saline within the aspirate collection container. For example, oftentimes the only indication that tissue has been removed from the patient is that the fluid within aspirate collection container has a pinkish hue, which may provide no indication as to the nature and amount of tissue removed from the patient.

[16] There, thus, is an ongoing need for dynamic aspiration system that can more accurately and precisely generate a pressure waveform at the distal end of the aspiration catheter using a relatively low source of vacuum and a relatively small amount of saline.

SUMMARY OF THE INVENTION

[17] In accordance with a first aspect of the present inventions, an aspiration modulation device for use with an aspiration catheter and a vacuum source is provided. An aspiration system may comprise this aspiration modulation device, the vacuum source, and the aspiration catheter.

[18] The aspiration modulation device comprises a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber. In one embodiment, the pressure manifold further has a vent inlet configured for fluidly coupling a pressurized fluid source to the pressure chamber, in which case, the aspiration modulation device may further comprise a fluid refill control element configured for selectively fluidly coupling the pressurized fluid source to the pressure chamber. When a fluid pressure within the pressure chamber drops below a threshold fluid pressure, the fluid refill control element may be configured for conveying pressure modulating fluid from the pressurized fluid source into the pressure chamber.

[19] The aspiration modulation device further comprises a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter. In one embodiment, the sensor is a force feedback sensor configured for measuring a force output of the fluid pressure oscillator. In another embodiment, the sensor is a pressure sensor, e.g., one configured for measuring a fluid pressure within the pressure chamber.

[20] The aspiration modulation device further comprises a controller configured for, in response to the measured parameter, dynamically modifying a waveform signal corresponding to a modulated therapeutic pressure waveform. In one embodiment, the controller is configured for selecting one of a plurality of different modulated therapeutic pressure waveforms, in which case, the waveform signal that is dynamically modified in response to the measured parameter corresponds to the selected one modulated therapeutic waveform. In an optional embodiment, the aspiration modulation device further comprises a user interface configured for receiving user input selecting the one modulated therapeutic waveform.

[21] The aspiration modulation device further comprises a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, thereby modulating a vacuum pressure within the pressure chamber (e.g., a baseline vacuum pressure applied by the vacuum source to the pressure chamber), such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

[22] In one embodiment, the fluid pressure oscillator comprises a pressure transduction element configured for interfacing with the pressure modulating fluid within the pressure chamber, an actuator (e.g., a voice coil actuator) configured for being operably coupled to the pressure transduction element, and a driver (e.g., an electrical driver) configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform. The actuator may be a linear actuator, in which case, the driver may be configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

[23] The pressure transduction element may comprise a movable manifold boundary, in which case, the driver may be configured for controlling the actuator to reciprocatably move the movable manifold boundary. The movable manifold boundary may be a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet. The driver may be configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm. In one embodiment, the actuator may be directly mechanically coupled to the diaphragm. For example, the actuator may comprise a rod directly mechanically coupled to the diaphragm. In this embodiment, the actuator may be removably coupled to the diaphragm. In another embodiment, the actuator may be fluidly coupled to the diaphragm.

[24] The pressure transduction element may be a secondary pressure transduction element (e.g., another diaphragm), in which case, the fluid pressure oscillator may further comprise a primary pressure transduction element fluidly coupled to the secondary pressure transduction element. For example, the primary pressure transduction element may be a piston, and the actuator may comprise a piston shaft mechanically coupled to the piston. In this embodiment, the manifold cavity may comprise a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the diaphragm is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber. The working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid. The primary pressure transduction element may be contained within the manifold cavity or may be external to the manifold cavity. In the latter case, the aspiration modulation device may further comprise a flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

[25] In an optional embodiment, the aspiration modulation device further comprises another pressure oscillator. The fluid pressure oscillator and the other pressure oscillator may be configured for concurrently and independently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform (e.g., a modulated complex pressure waveform having at least two different base frequencies).

[26] In another optional embodiment, the controller is further configured for generating a plurality of waveform signals respectively corresponding to a plurality of different modulated diagnostic pressure waveforms (e.g., having different frequencies), in which case, the fluid pressure oscillator may be configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber sequentially in accordance with the plurality of waveform signals, thereby modulating the vacuum pressure within the pressure chamber. In this embodiment, the aspiration modulation device further comprises a processor configured for analyzing the measured parameter in response to the modulation of the vacuum pressure within the pressure chamber, and generating or selecting the modulated therapeutic pressure waveform based on the analysis of the measured parameter. In one example, the controller, in response to a thrombus clogging the aspiration catheter, may be configured for generating the plurality of waveform signals, and the processor may be configured for determining one or more characteristics of the thrombus based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined one or more characteristics of the thrombus. In another example, the controller, when the aspiration catheter is connected to the aspiration modulation device, may be configured for generating the plurality of waveform signals, and the processor may be configured for determining a type of the aspiration catheter based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined type of the aspiration catheter.

[27] In still another optional embodiment, the aspiration modulation device further comprises a master unit comprising a first casing containing the controller, and a slave unit comprising a second casing containing the pressure manifold and at least a portion of the fluid pressure oscillator. This aspiration modulation device may further comprise flexible fluidic tubing fluidly coupling the master unit and slave unit to each other. The master unit may be configured for being inserted into the second casing of the slave unit and for being electrically coupled to the slave unit when inserted into the second casing of the slave unit.

[28] In accordance with a second aspect of the present inventions, another aspiration modulation device for use with an aspiration catheter and a vacuum source is provided. An aspiration system may comprise this aspiration modulation device, the vacuum source, and the aspiration catheter.

[29] The aspiration modulation device comprises a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber.

[30] The aspiration modulation device further comprises a fluid pressure oscillator comprising a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet, the fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm, thereby modulating a vacuum pressure (e.g., a baseline vacuum pressure applied by the vacuum source to the pressure chamber) within the pressure chamber.

[31] In one embodiment, the fluid pressure oscillator further comprises an actuator (e.g., a voice coil actuator) configured for being operably coupled to the diaphragm, and a driver (e.g., an electrical driver) configured for controlling the actuator to physically move the diaphragm in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber. The actuator may be a linear actuator, in which case, the driver may be configured for controlling the actuator to physically move the diaphragm in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber. The driver may be configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm. In one embodiment, the actuator may be directly mechanically coupled to the diaphragm. For example, the actuator may comprise a rod directly mechanically coupled to the diaphragm. In this embodiment, the actuator may be removably coupled to the diaphragm. In another embodiment, the actuator may be fluidly coupled to the diaphragm.

[32] This diaphragm may be a secondary pressure transduction element (e.g., another diaphragm), in which case, the fluid pressure oscillator may further comprise a primary pressure transduction element (e.g., another diaphragm) fluidly coupled to the secondary pressure transduction element. For example, the primary pressure transduction element may be a piston, and the actuator may comprise a piston shaft mechanically coupled to the piston. In this embodiment, the manifold cavity may comprise a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the secondary pressure transduction element is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber. The working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid. The primary pressure transduction element may be contained within the manifold cavity or may be external to the manifold cavity. In the latter case, the aspiration modulation device may further comprise a flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

[33] In an optional embodiment, the aspiration modulation device further comprises a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform. In this embodiment, the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm in accordance with the waveform signal, thereby modulating the vacuum pressure within the pressure chamber. In this embodiment, the aspiration modulation device may further comprise a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, in which case, the controller may be configured for, in response to the measured parameter, dynamically modifying the waveform signal, and the fluid pressure oscillator may be configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

[34] In another optional embodiment, the aspiration modulation device further comprises a master unit comprising a first casing containing the controller, and a slave unit comprising a second casing containing the pressure manifold and at least a portion of the fluid pressure oscillator. The aspiration modulation device may further comprise flexible fluidic tubing fluidly coupling the master unit and slave unit to each other. The master unit may be configured for being inserted into the second casing of the slave unit and for being electrically coupled to the slave unit when inserted into the second casing of the slave unit.

[35] In accordance with a third aspect of the present inventions, still another aspiration modulation device for use with an aspiration catheter and a vacuum source is provided. An aspiration system may comprise this aspiration modulation device, the vacuum source, and the aspiration catheter.

[36] The aspiration modulation device comprises a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber.

[37] The aspiration modulation device further comprises a plurality of fluid pressure oscillators configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating a vacuum pressure within the pressure chamber (e.g., a baseline vacuum pressure applied by the vacuum source to the pressure chamber). In one embodiment, the plurality of fluid pressure oscillators is configured for independently oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber.

[38] In one embodiment, each of the plurality of fluid pressure oscillators comprises a pressure transduction element (e g., a diaphragm) configured for interfacing with the pressure modulating fluid within the pressure chamber, an actuator (e.g., a voice coil actuator) configured for being operably coupled to the pressure transduction element, and a driver (e.g., an electrical driver) configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform. The actuator may be a linear actuator, in which case, the driver may be configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

[39] The pressure transduction element of each respective fluid pressure oscillator may comprise a movable manifold boundary, in which case, the driver may be configured for controlling the actuator to reciprocatably move the movable manifold boundary. The movable manifold boundary may be a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet. The driver may be configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm. The diaphragms of two of the plurality of fluid pressure oscillators may oppose each other, such that the manifold cavity is divided between the pressure chamber between the opposing diaphragms, and working chambers external to the opposing diaphragms that are fluidly isolated from the vacuum inlet and the vacuum outlet, wherein two fluid pressure oscillators are configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the respective diaphragms, thereby modulating the vacuum pressure within the pressure chamber.

[40] The actuator of each respective fluid pressure oscillator may be a linear actuator, in which case, the driver of each respective fluid pressure oscillator may be configured for controlling the actuator to physically move the diaphragm in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber. The driver may be configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm. In one embodiment, the actuator of each respective fluid pressure oscillator may be directly mechanically coupled to the diaphragm of each respective fluid pressure oscillator. For example, the actuator of each respective fluid pressure oscillator may comprise a rod directly mechanically coupled to the diaphragm of each respective fluid pressure oscillator. In this embodiment, the actuator of each respective fluid pressure oscillator may be removably coupled to the diaphragm of each respective fluid pressure oscillator. In another embodiment, the actuator may be fluidly coupled to the diaphragm.

[41] In an optional embodiment, the aspiration modulation device further comprises a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform (e.g., a complex pressure waveform having at least two different base frequencies). In this embodiment, the plurality of fluid pressure oscillators are configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the waveform signal, thereby modulating the vacuum pressure within the pressure chamber. In this embodiment, the aspiration modulation device may further comprise a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, in which case, the controller may be configured for, in response to the measured parameter, dynamically modifying the waveform signal, and the plurality of fluid pressure oscillators are configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

[42] In accordance with a fourth aspect of the present inventions, yet another aspiration modulation device for use with an aspiration catheter and a vacuum source is provided. An aspiration system may comprise this aspiration modulation device, the vacuum source, and the aspiration catheter.

[43] The aspiration modulation device comprises a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber, and a vent inlet configured forfluidly coupling the pressurized fluid source (e.g., atmospheric pressure) to the pressure chamber.

[44] The aspiration modulation device further comprises a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating a vacuum pressure within the pressure chamber. In one embodiment, the fluid pressure oscillator comprises a pressure transduction element configured for interfacing with the pressure modulating fluid within the pressure chamber, an actuator (e.g., a voice coil actuator) configured for being operably coupled to the pressure transduction element, and a driver (e.g., an electrical driver) configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber. The actuator may be a linear actuator, in which case, the driver may be configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber. The pressure transduction element may comprise a movable manifold boundary, in which case, the driver may be configured for controlling the actuator to reciprocatably move the movable manifold boundary. The movable manifold boundary may be a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamberfluidly isolated from the vacuum inlet and the vacuum outlet. The driver may be configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm. In one embodiment, the actuator may be directly mechanically coupled to the diaphragm. For example, the actuator may comprise a rod directly mechanically coupled to the diaphragm. In this embodiment, the actuator may be removably coupled to the diaphragm. In another embodiment, the actuator may be fluidly coupled to the diaphragm.

[45] The aspiration modulation device further comprises a fluid refill control element (e.g., check valve) configured for selectively fluidly coupling the pressurized fluid source to the pressure chamber. In one embodiment, when a fluid pressure within the pressure chamber drops below a threshold fluid pressure, the fluid refill control element is configured for conveying pressure modulating fluid from the pressurized fluid source into the pressure chamber.

[46] In an optional embodiment, the aspiration modulation device further comprises a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform. In this embodiment, the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the pressure transduction element in accordance with the waveform signal, thereby modulating the vacuum pressure within the pressure chamber. In this embodiment, the aspiration modulation device may further comprise a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, in which case, the controller may be configured for, in response to the measured parameter, dynamically modifying the waveform signal, and the fluid pressure oscillator may be configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

[47] In accordance with a fifth aspect of the present inventions, yet another aspiration modulation device for use with an aspiration catheter and a vacuum source is provided. An aspiration system may comprise this aspiration modulation device, the vacuum source, and the aspiration catheter.

[48] The aspiration modulation device comprises a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform, and a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber. This aspiration modulation device further comprises a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the waveform signal, thereby modulating a vacuum pressure within the pressure chamber (e.g., a baseline vacuum pressure applied by the vacuum source to the pressure chamber).

[49] The aspiration modulation device further comprises a master unit comprising a casing carrying the controller, and a slave unit comprising a casing carrying at least a portion of the pressure manifold and at least a portion of the fluid pressure oscillator. The master unit is configured for being operably coupled to and operably decoupled from the slave unit. In one embodiment, the casing of the master unit carries at least another portion of the fluid pressure oscillator. In another embodiment, the master unit is configured for being inserted into the slave unit.

[50] In still another embodiment, the fluid pressure oscillator comprises a pressure transduction element carried by the slave unit and configured for interfacing with the pressure modulating fluid within the pressure chamber, an actuator (e.g., a voice coil actuator) configured for being operably coupled to the pressure transduction element, and a driver (e.g., an electrical driver) configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform. In this embodiment, the pressure transduction element is carried by the casing of the slave unit, and the driver is carried by the casing of the master unit. The actuator may be carried by the casing of the master unit. The respective casings of the master unit and the slave unit may be casing portions that are mechanically affixed directly to each other to form a single casing. [51] The actuator may be a linear actuator, in which case, the driver may be configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber. The pressure transduction element may comprise a movable manifold boundary, in which case, the driver may be configured for controlling the actuator to reciprocatably move the movable manifold boundary. The movable manifold boundary may be a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet. The driver may be configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm. In one embodiment, the actuator may be directly mechanically coupled to the diaphragm. For example, the actuator may comprise a rod directly mechanically coupled to the diaphragm. In this embodiment, the actuator may be removably coupled to the diaphragm. In another embodiment, the actuator may be fluidly coupled to the diaphragm.

[52] The pressure transduction element may be a secondary pressure transduction element (e.g., another diaphragm), in which case, the fluid pressure oscillator may further comprise a primary pressure transduction element fluidly coupled to the secondary pressure transduction element. For example, the primary pressure transduction element may be a piston, and the actuator may comprise a piston shaft mechanically coupled to the piston. In this embodiment, the manifold cavity may comprise a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the diaphragm is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber. The working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid. The primary pressure transduction element may be contained within the manifold cavity or may be external to the manifold cavity. In the latter case, the aspiration modulation device may further comprise a flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

[53] In an optional embodiment, this aspiration modulation further comprises a sensor carried by the slave unit and configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, wherein the controller is configured for, in response to the measured parameter, dynamically modifying the waveform signal, and wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

[54] In accordance with a sixth aspect of the present inventions, an aspiration device for use with an aspiration catheter and a vacuum source is provided. An aspiration system may comprise this aspiration device, the vacuum source, and the aspiration catheter.

[55] The aspiration device comprises pressure manifold comprising a manifold cavity having a pressure chamber and a working chamber, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber. The aspiration device further comprises a diaphragm affixed within the manifold cavity for fluidly isolating the pressure chamber from the working chamber. The diaphragm is configured for applying a clog clearing pressure to aspiration fluid contained in the pressure chamber in response to a force applied to the diaphragm from the working chamber.

[56] In one embodiment, the vacuum outlet is configured for fluidly coupling the vacuum source to the pressure chamber during the application of the clog clearing pressure by the diaphragm to the aspiration fluid contained in the pressure chamber. The aspiration fluid contained in the pressure chamber is a pressure modulating fluid having a variable volume, in which case, the aspiration device may further comprise a fluid pressure oscillator configured for applying an oscillatory force to the diaphragm. The diaphragm may be configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in response to the oscillatory force applied to the diaphragm, thereby modulating a vacuum pressure within the pressure chamber (e.g., in any one of the variety of manners discussed above).

[57] In another embodiment, diaphragm is further configured for fluidly decoupling the vacuum source from the pressure chamber by sealing the vacuum outlet prior to the application of the clog clearing pressure by the diaphragm to the aspiration fluid contained in the pressure chamber. In this embodiment, the diaphragm may have a sealing region configured for contacting the vacuum outlet to seal the vacuum outlet from the pressure chamber, and a deflectable region configured for deflecting within the pressure chamber to apply the clog clearing pressure to the aspiration fluid contained in the pressure chamber. The sealing region may be, e.g., a center circular region of the diaphragm, and the deflectable region may be, e.g., an annular region of the diaphragm.

[58] In this embodiment, the diaphragm may be configured for sealing the vacuum outlet from the pressure chamber in response to a pressure in the working chamber greater than a sealing pressure threshold. The diaphragm may be configured for applying the clog clearing pressure to the aspiration fluid contained in the pressure chamber in a dedicated manner. The diaphragm may be further configured for fluidly recoupling the vacuum source to the pressure chamber by unsealing the vacuum outlet in response to a pressure in the working chamber less than an unsealing pressure threshold. In this case, the unsealing pressure threshold may be less than the sealing pressure threshold when the aspiration catheter remains clogged with a thrombus or greater than the sealing pressure threshold when a thrombus in the aspiration catheter is cleared. In an optional embodiment, the aspiration device may further comprise a spring configured for biasing the diaphragm to unseal the vacuum outlet from the pressure chamber and/or the diaphragm may have a passive restorative force for biasing the diaphragm to unseal the vacuum outlet from the pressure chamber.

[59] If the diaphragm is further configured for fluidly recoupling the vacuum source to the pressure chamber, the clog clearing pressure that the diaphragm is configured for applying to the aspiration fluid contained in the pressure chamber may be a pressure pulse output, in which case, the diaphragm may be configured for applying the pressure pulse output to the aspiration fluid contained in the pressure chamber in response to a pressure pulse input applied to a working fluid contained in the working chamber. The pressure of a peak magnitude of the pressure pulse input is above the sealing pressure threshold. The clog clearing pressure that the diaphragm is configured for applying to the aspiration fluid contained in the pressure chamber may optionally comprise a series of pressure pulse outputs, in which case, the diaphragm may be configured for applying the series of pressure pulse outputs to the aspiration fluid contained in the pressure chamber in response to the series of pressure pulse inputs applied by the pressure control device to the working fluid contained in the working chamber. [60] In this embodiment, the diaphragm may be configured for coupling the vacuum source to the pressure chamber in response to a removal of the pressure pulse input from the working fluid contained in the working chamber, in which case, the pressure of a base magnitude of the pressure pulse input may be below the unsealing pressure threshold. Optionally, the diaphragm may be configured for maintaining the decoupling of the vacuum source from the pressure chamber in response to a removal of the pressure pulse input from the working fluid contained in the working chamber, in which case, the pressure of a base magnitude of the pressure pulse input may be above the unsealing pressure threshold.

[01] The aspiration device may further comprise a pressure control device configured for applying the pressure pulse input to the working fluid contained in the working chamber. In one example, the pressure control device may comprise a three- way valve configured for applying the pressure pulse input to the working fluid contained in the working chamber by alternately fluidly coupling the working chamber to atmosphere and another vacuum source. In another example, the pressure control device may comprise a pressure generator configured for applying the pressure pulse input to the working fluid contained in the working chamber by generating the pressure pulse input. The aspiration device may further comprise a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, in which case, the pressure control device may be configured for applying the pressure pulse input to the working fluid contained in the working chamber in response to the measured parameter. In an optional embodiment, the diaphragm may be configured for modulating the pressure pulse input, such that the pressure pulse output corresponds to the modulated pressure pulse input.

[02] Other and further aspects and features of embodiments of the disclosed inventions will become apparent from the ensuing detailed description in view of the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

[03] The drawings illustrate the design and utility of preferred embodiments of the disclosed inventions, in which similar elements are referred to by common reference numerals. It should be noted that the figures are not drawn to scale and that elements of similar structures or functions are represented by like reference numerals throughout the figures. It should also be noted that the figures are only intended to facilitate the description of the embodiments. They are not intended as an exhaustive description of the invention or as a limitation on the scope of the invention, which is defined only by the appended claims and their equivalents. In addition, an illustrated embodiment of the disclosed inventions needs not have all the aspects or advantages shown. Further, an aspect or an advantage described in conjunction with a particular embodiment of the disclosed inventions is not necessarily limited to that embodiment and can be practiced in any other embodiments even if not so illustrated.

[04] In order to better appreciate how the above-recited and other advantages and objects of the disclosed inventions are obtained, a more particular description of the disclosed inventions briefly described above will be rendered by reference to specific embodiments thereof, which are illustrated in the accompanying drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:

[05] Fig. 1 is a concept diagram of a prior art dual-valve cyclical aspiration system;

[06] Fig. 2 is a timing diagram illustrating an exemplary pressure waveform generated by the dual-valve cyclical aspiration system of Fig. 1 ;

[07] Fig. 3 is a block diagram of one embodiment of a dynamic aspiration system constructed in accordance with the present inventions;

[08] Fig. 4 is a plan view of an exemplary aspiration catheter used in the dynamic aspiration system of Fig. 3;

[09] Fig. 5 is a plan view of the distal end of the aspiration catheter of Fig. 4 in use for aspirating an occlusion from the vasculature of a patient;

[10] Fig. 6 is a timing diagram illustrating an exemplary pressure waveform generated by the dynamic aspiration system of Fig. 3;

[11] Figs. 7A-7C are plan views of one embodiment of an aspiration modulation device that can be employed in the dynamic aspiration system of Fig. 3, particularly showing a fluid pressure oscillator of the aspiration modulation device in three different states;

[12] Figs. 8A-8C are plan views of another embodiment of an aspiration modulation device that can be employed in the dynamic aspiration system of Fig. 3, particularly showing a fluid pressure oscillator of the aspiration modulation device in three different states;

[13] Figs. 9A-7G are plan views of still another embodiment of an aspiration modulation device that can be employed in the dynamic aspiration system of Fig. 3, particularly showing dual fluid pressure oscillators of the aspiration modulation device in seven different states;

[14] Figs. 10A-10C are plan views of yet another embodiment of an aspiration modulation device that can be employed in the dynamic aspiration system of Fig. 3, particularly showing a portion of a fluid pressure oscillator of master unit of the aspiration modulation device in three different states;

[15] Figs. 11A-11C are plan views of the aspiration modulation device of Figs. 10A-10C, particularly showing a portion of the fluid pressure oscillator of a slave unit of the aspiration modulation device in three different states;

[16] Fig. 12 is a perspective view of yet another embodiment of an aspiration modulation device that can be employed in the dynamic aspiration system of Fig. 3;

[17] Fig. 13 is a perspective view of master and slave units of the aspiration modulation device of Fig. 12;

[18] Figs. 14A-14C are plan views of different states of an embodiment of an aspiration pulsing device constructed in accordance with the present inventions;

[19] Fig. 15A is a top view of one embodiment of a diaphragm that can be used in the aspiration pulsing device of Figs. 14A-14C;

[20] Fig. 1 SB is a cutaway perspective view of the diaphragm of Fig. 15A;

[21] Figs. 16A-16C are timing diagrams of different pressure waveform inputs and resulting pressures in the aspiration pulsing device of Figs. 14A-14C;

[22] Figs. 17A-17C are plan views of two embodiments of pressure control devices that can be used with the aspiration pulsing device of Figs. 14A-14C;

[23] Figs. 18A-18C are timing diagrams of different pressure waveforms inputs that can be input into the aspiration pulsing device of Figs. 14A-14C; and

[24] Fig. 19 is a timing diagram of a pressure waveform input and a resulting modulated pressure waveform output in the aspiration pulsing device of Figs. 14A- 14C DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

[25] Referring to Fig. 3, one embodiment of a dynamic aspiration system 20 constructed accordance with the disclosed inventions will now be described. The dynamic aspiration system 20 generally comprises an aspiration catheter 22, a vacuum source 24, a pressurized fluid source 26, an aspirate collection container 28, and an aspiration modulation device 30.

[26] Referring further to Figs. 4 and 5, the aspiration catheter 22 comprises an elongated catheter body 32, an aspiration lumen 34 (shown in phantom in Fig. 5) extending through the catheter body 32 between a proximal end 36 and a distal end 38 of the catheter body 32. The proximal end 36 of the aspiration catheter 22 remains outside of a vasculature 100 of the patient and accessible to the operator when the dynamic aspiration system 20 is in use, while the distal end 38 of the catheter body 32 is sized and dimensioned to reach an occlusion 102 (e.g., a thrombus) within a remote location of the vasculature 100 of the patient, as best shown in Fig. 5. The aspiration catheter 22 comprises a distal inlet port 40 in communication with the aspiration lumen 34 of the aspiration catheter 22, and into which the thrombus 102 is ingested by the aspiration catheter 22. The thrombus 102 may be wholly ingested into the aspiration catheter 22 or may be broken up into pieces and ingested piece-by-piece into the aspiration catheter 22.

[27] The aspiration catheter 22 may include a plurality of regions along its length having different configurations and/or characteristics. For example, a distal portion of the catheter body 32 may have an outer diameter less than the outer diameter of a proximal portion of the catheter body 32 to reduce the profile of the distal portion of the catheter body 32 and facilitate navigation in tortuous vasculature. Furthermore, the distal portion of the catheter body 32 may be more flexible than the proximal portion of the catheter body 32. Generally, the proximal portion of the catheter body 32 may be formed from material that is stiffer than the distal portion of the catheter body 32, so that the proximal portion has sufficient pushability to advance through the vasculature 100 of the patient, while the distal portion may be formed of a more flexible material so that it may remain flexible and track more easily over a guidewire to access remote locations in tortuous regions of the vasculature 100. The catheter body 32 may be composed of suitable polymeric materials, metals and/or alloys, such as polyethylene, stainless steel or other suitable biocompatible materials or combinations thereof. In some instances, the proximal portion of the catheter body 32 may include a reinforcement layer, such a braided layer or coiled layer to enhance the pushability of the catheter body 32. The catheter body 32 may include a transition region between the proximal portion and the distal portion of the catheter body 32.

[28] Referring back to Fig. 3, in operation, the vacuum source 24 applies a baseline vacuum pressure to the aspiration modulation device 30. The base vacuum pressure is below the mean arterial pressure (MAP) of a patient, and preferably below atmospheric pressure, and thus, can be considered a vacuum capable of aspirating the thrombus 102 within the aspiration lumen 34 of the aspiration catheter 22 (shown in Fig. 5) This baseline vacuum pressure may be controlled and adjusted as needed by the user for aspirating tissue. Over any given time period during a tissue removal procedure, the user may set the level of baseline vacuum pressure to be constant or may vary the vacuum level. The vacuum source 24 can be, e.g., conventional a pump (e.g., a rotary vane, diaphragm, peristaltic or Venturi pump) or a syringe, configured for generating a low pressure (i.e., a base vacuum pressure) within the aspiration lumen 34 of the aspiration catheter 22.

[29] Significantly, due to the employment of the aspiration modulation device 30 (described in further detail below), the vacuum source 24 may be operated at relatively low vacuum pressures (e.g., 30 to 60 kPa (absolute)/-70 to -40 kPa (gauge), which is higher in an absolute pressure sense than what is required for a valve-based system. Because the baseline vacuum pressure of the vacuum source 24 need not be strong, the vacuum source 24 may be lower performing or may even take the form of house vacuum lines. The vacuum source 24 may comprise a regulator (not shown) for maintaining the output of the vacuum source 24 at a consistent level.

[30] The pressurized fluid source 26 may be, e.g., a reservoir containing a liquid at atmospheric pressure, such as saline (e.g., a saline drip bag), or ambient air. It should be appreciated that the pressurized fluid source 26 is pressurized in that the fluid has a pressure that is higher than the lowest vacuum level (i.e., highest baseline vacuum pressure) achieved in the aspiration lumen 34 of the aspiration catheter 22 when the vacuum source 24 is operating. Thus, even though the pressurized fluid source 26 in the illustrated embodiment may be under low pressure (i.e., at ambient or one atmosphere absolute pressure), the pressurized fluid source 26 is pressurized relative to the pressures experienced by the aspiration lumen 34 of the aspiration catheter 22 during operation of the vacuum source 24. The aspirate collection container 28 may be any suitable receptacle in fluid communication with the vacuum source 24 via an exhaust line for enabling collection and disposal of aspirated tissue in a sterile manner. Alternatively, the aspirate collection container 28 may be located between the vacuum source 24 and the aspiration catheter 22. A safety valve (not shown) may be provided within the aspirate collection container 28 to prevent fluid or material entering the vacuum source 24.

[31] While the aspiration catheter 22, vacuum source 24, pressurized fluid source 26, and aspirate collection container 28 may be conventional in nature, the aspiration modulation device 30 is unconventional. In particular, the aspiration modulation device 30 provides an interface between the aspiration catheter 22, vacuum source 24, and pressurized fluid source 26 that, instead of using a valving system to alternately pressurize and depressurize the aspiration catheter 22, modulates a pressure within the aspiration lumen 34 of the aspiration catheter 22. As a result, ingestion of the thrombus 102 by the aspiration catheter 22 will be facilitated during no-flow or low-flow conditions (e.g., if the thrombus 102 clogs the aspiration lumen 34 of the aspiration catheter 22 or otherwise there is a flow anomaly in the aspiration circuit of the dynamic aspiration system 20). Furthermore, by modulating the vacuum pressure within the aspiration lumen 34 of the aspiration catheter 22, the baseline vacuum pressure applied by the vacuum source 24 to the aspiration catheter 22 can be relatively low, such that blood loss and/or the occurrence of vessel collapse may be minimized during free-flow conditions (e.g., when the aspiration lumen 34 is not clogged and the aspiration circuit of the dynamic aspiration system 20 is operating as intended).

[32] Furthermore, the aspiration modulation device 30 may modulate the vacuum pressure within the aspiration lumen 34 of the aspiration catheter 22 without using an excessive amount of saline, which may only be used to initially prime the dynamic aspiration system 20. As a result, much of the material contained within the aspirate collection container 28 will be tissue removed from the patient, thereby allowing the nature and the amount of such tissue to be determined via a quick inspection of the aspiration collection container 28.

[33] In the illustrated embodiment, the aspiration modulation device 30 modulates the vacuum pressure within the aspiration lumen 34 of the aspiration catheter 22 by modulating the baseline vacuum pressure applied by the vacuum source 24 to the aspiration catheter 22 (i.e., by oscillating the fluid pressure within the aspiration catheter 22 around the baseline vacuum pressure). For example, as illustrated in Fig. 6, the aspiration modulation device 30 may generate a therapeutic pressure waveform 1 10 that oscillates around the baseline vacuum pressure (i.e. , the pressure drops below the baseline vacuum pressure, then rises above the baseline vacuum pressure, and in the illustrated case above vent pressure (i.e., the pressure of the pressurized fluid source 26), drops back below the vent pressure and then below the baseline vacuum pressure, etc.). Thus, in contrast to dual-valve aspiration systems that generate a pressure waveform 12 (illustrated in Fig. 2) that varies between the baseline vacuum pressure and the vent pressure (i.e., the maxima (peaks) of the pressure waveform 12 is essentially the vent pressure, and the minima (valleys) of the pressure waveform 12 is essentially the vacuum pressure), the maxima and minima of the therapeutic pressure waveform 110 are not determined by the baseline vacuum pressure and the vent pressure.

[34] It should be appreciated that, although the baseline vacuum pressure applied by the vacuum source 24 to the aspiration modulation device 30 is modulated, such that the maxima and minima of the therapeutic pressure waveform 110 illustrated in Fig. 6 are equidistant relative to the baseline vacuum pressure (i.e., the minimum and maximum pressures are equally offset from the baseline vacuum pressure), a vacuum pressure other than the baseline vacuum pressure may be modulated by the aspiration modulation device 30, such that the maxima and minima of the therapeutic pressure waveform 110 may be non-equidistant relative to the baseline vacuum pressure (i.e., the maxima are offset from the baseline vacuum pressure a greater distance than the minima are offset from the baseline vacuum pressure, orvice versa). Furthermore, although the maxima of the therapeutic pressure waveform 110 illustrated in Fig. 6 are higher than the vent pressure, it should be appreciated that the peaks of the therapeutic pressure waveform 110 may be below the vent pressure. Furthermore, although the magnitudes of all the maxima and the magnitudes of all the minima of the therapeutic pressure waveform 110 illustrated in Fig. 6 are uniform, the magnitudes of the maxima and/or the magnitudes of the minima of the therapeutic pressure waveform 110 illustrated in Fig. 6 may be non-uniform. Preferably, the maxima of the therapeutic pressure waveform 110 are below the mean arterial pressure (MAP) of the patient, so that any thrombus 102 that is captured within the distal end 38 of the catheter body 32 is not ejected back out into the artery of the patient. Under certain conditions, the maxima of the therapeutic pressure waveform 110 may be modulated to momentarily exceed the MPAP of the patient, thus amplifying the force range applied to the thrombus 102. This enhanced force can effectively weaken the resistance of the thrombus 102 or fatigue the network of the thrombus 102, thereby facilitating more efficient ingestion without causing the distal movement of the thrombus 102.

[35] Significantly, the aspiration modulation device 30 modulates the baseline vacuum pressure applied by the vacuum source 24 to the aspiration catheter 22 in a manner that accurately and precisely generates a desired modulated therapeutic pressure waveform at the distal end 38 of the catheter body 32. Such modulated therapeutic pressure waveform may be complex. For example, as illustrated in Fig. 6, the modulated therapeutic pressure waveform 110 comprises different complex components, including rectangular components 112, sinusoidal components 114, and cut-sine or sawtooth components 116. Of course, alternative modulated therapeutic pressure waveforms may be simple, e.g., may be purely sinusoidal, purely rectangular, etc. Indeed, as will be described in further detail below, the modulated therapeutic pressure waveform 110 may be arbitrary in that aspiration modulation device 30 may be programmed (e.g., pre-programmed during manufacture, programmed during subsequent system upgrades, programmed by the user, etc.) to generate any modulated therapeutic pressure waveform 110 (therapeutic or diagnostic) having a desired shape, desired frequency, desired duty cycle, desired amplitude, desired midpoint, etc. or the aspiration modulation device 30 may customize such programmed modulated therapeutic pressure waveform 110 to a diagnostic scenario.

[36] Significantly, the aspiration modulation device 30 is capable of accurately and precisely generating a desired modulated pressure waveform at the distal end 38 of the catheter body 32 using pressure feedback control. In particular, the aspiration modulation device 30 may modulate the baseline vacuum pressure applied by the vacuum source 24 to the aspiration catheter 22, such that fluid pressure measured (directly or indirectly) at the distal end 38 of the catheter body 32 tracks the desired pressure waveform.

[37] Notably, the use of pressure feedback to generate a desired modulated pressure waveform in an aspiration catheter should be contrasted with aspiration systems that may modulate the baseline vacuum pressure in an open loop manner or using other feedback, such as positioning feedback (e.g., using an encoder or positioning sensor), which may be susceptible to decorrelation between controlled modulation of the baseline vacuum pressure and the desired pressure waveform at the distal end 38 of the catheter body 32 due to, e.g., gas bubbles in the dynamic aspiration system, and may also have a relatively slow response time.

[38] In contrast, when using pressure feedback, the controlled modulation of the baseline vacuum pressure will be much more correlated to the fluid pressure at the distal end 38 of the catheter body 32, and may have a faster response time. Thus, the aspiration modulation device 30 may operate without actuator sensors that simplifies the feedback in closed-loop control, and further to allow quick response and high- modulation capability. Such an arrangement avoids controls related, load-induced, motion modulations in the dynamic aspiration system 20, thereby enabling high-speed force/torque output for a more consistent modulated pressure waveform. For example, direct frequency/speed modulation, direct amplitude assigned pulsing, or programmable parametric inputs of a transfer function are all possible modes of operation when employing pressure feedback control.

[39] The aspiration modulation device 30 may optionally perform an in situ diagnostic procedure during active aspiration by modulating an input pressure waveform (e.g., singlet pulses, frequency sweeps, or chirps), while simultaneously monitoring the pressure response to the modulated input pressure waveform. The aspiration modulation device 30 may then analyze the monitored pressure response and detect or discriminate in-vivo conditions, such as aspiration flow conditions (e.g., free flow (no clot present), mixed flow (active clot aspiration), and no flow (distal catheter occlusion by clot), flow phase type (e.g., fluid only, mixed clot and fluid, mixed fluid and gas, etc.), clot characteristics (e.g., clot elasticity, clot friability, etc.), plugging of the distal inlet port 40 of the aspiration catheter 22 by a vascular wall, the amount of vascular flow attenuation caused by the aspiration catheter 22, etc. For example, time domain responses to modulated waveforms can, for example, facilitate the understanding of vessel patency. The response amplitude and response time constant to modulated waveforms can provide differentiation of free flow versus clogged conditions. Frequency domain analysis of responses from a modulated scan can depict tissue properties, clot elasticities, and clot types. Each of the different type of pressure modulations may have different diagnostic capabilities depending on the type of information to be acquired. Such information can be used in a manner such that, when sustained continuous flow is detected following complete clot aspiration, the aspiration modulation device 30 can turn off (or the intensity of the pressure variations of the baseline vacuum pressure can be lowered) and the baseline vacuum pressure can be lowered.

[40] In one advantageous embodiment, the aspiration modulation device 30 may be operated to dynamically tune the dynamic aspiration system 20 in situ in response to a sensed condition. For example, the aspiration modulation device 30 may monitor the aspiration flow rate to determine the flow condition of the aspiration, and automatically modify the desired modulated therapeutic pressure waveform in response to monitored flow condition. In one embodiment, the aspiration flow rate can be determined via modulation of an input pressure waveform and analysis of pressure response. Alternatively, a flow sensor may be employed to directly measure the aspiration flow rate. In the case of a determined free flow condition, the aspiration modulation device 30 may switch to a “free flow” mode, e.g., by applying a relatively low duty cycle, along with a relatively high absolute baseline vacuum pressure, to the modulated pressure waveform. In the case of a determined mixed flow condition, the aspiration modulation device 30 may switch to an “active ingestion” mode by, e.g., applying a relatively moderate duty cycle, along with a relatively moderate absolute baseline vacuum pressure, to the modulated pressure waveform. In the case of a determined no flow condition, the aspiration modulation device 30 may switch to a “clog” mode, e.g., by applying a relatively high duty cycle, along with a relatively low absolute baseline vacuum pressure, to the modulated pressure waveform. As another example, the aspiration modulation device 30 may monitor the aspiration flow rate to determine the flow phase type (e.g., fluid only, mixed clot and fluid, mixed fluid and gas, etc.) and automatically select or modify the modulated pressure waveform in accordance with the determined flow phase type.

[41] In another advantageous embodiment, the aspiration modulation device 30 may be operated to interrogate a thrombus by generating a multitude of different modulated diagnostic pressure waveforms (e.g., by modulating the amplitude, frequency, duty cycle, and/or shape of an input pressure waveform), while simultaneously monitoring the pressure response to such modulated diagnostic pressure waveforms.

[42] For example, in response to a clog in the distal end 38 of the catheter body 32, the aspiration modulation device 30 may implement a pressure frequency sweep of the input pressure waveform (i.e., generates a multitude of diagnostic pressure waveforms having different frequencies) while simultaneously monitoring the pressure response to the pressure frequency sweep. The aspiration modulation device 30 may then perform a spectral analysis of the monitored pressure response to identify the optimal frequency to disrupt an individual clot (with unknown composition) (e.g., the frequency that provides the maximal feedback pressure response), and then automatically modulate the baseline vacuum pressure at that identified frequency until the clot has been fully ingested. For example, the frequency (or frequency range) required to ingest a clot may be dependent on the modulus of the clot.

[43] For example, if it is determined that the clot is relatively hard, the aspiration modulation device 30 may be automatically operated in a “hard clot” mode that modulates the baseline vacuum pressure at a first frequency (or within a frequency range centered on the first frequency), and if it is determined that the clot is relatively soft, the aspiration modulation device 30 may be automatically operated in a “soft clot” mode that modulates the baseline vacuum pressure at a second different frequency (or within a frequency range centered on the second frequency). In the “hard clot” mode, the baseline vacuum pressure may be modulated at a relatively high frequency, but relatively low amplitude, such that the clot is ingested in a piecemeal fashion (i.e., pieces of the clot are incrementally broken off and ingested). In the “soft clot” mode, the baseline vacuum pressure may be modulated at a relatively high amplitude, but a relatively high frequency, such that the clot is ingested whole.

[44] Alternatively or additionally, the aspiration modulation device 30 may implement a pressure amplitude sweep (i.e., generates a multitude of pressure waveforms having different amplitudes) and/or pressure duty cycle sweep (i.e., generates a multitude of pressure waveforms having different duty cycles) while simultaneously monitoring the pressure response to the pressure amplitude and/or pressure duty cycle sweep to identify the optimal pressure amplitude and/or pressure duty cycle to disrupt an individual clot (with unknown composition).

[45] In still another advantageous embodiment, the aspiration modulation device 30 may be operated to dynamically tune the dynamic aspiration system 20 apriori, e.g., to pre-screen the aspiration catheter 22, when connected to the aspiration modulation device 30, but prior to its introduction into the patient. The aspiration modulation device 30 may then calibrate the dynamic aspiration system 20 to the specific aspiration catheter 22 (not only the type and size of the aspiration catheter 22, but also the specific aspiration catheter 22 that is currently used). [46] For example, the distal end 38 of the catheter body 32 can be plugged, information regarding the clinical scenario can be input into the aspiration modulation device 30 (e.g., the vessel in which the thrombus is located, local atmospheric pressure, patient blood pressure, temperature, blood viscosity, etc.), and the aspiration modulation device 30 may generate a plurality of different diagnostic pressure waveforms (e.g., by performing a frequency sweep of an input pressure waveform), while simultaneously monitoring the pressure response to the modulated input pressure waveform.

[47] The aspiration modulation device 30 may customize or tune a modulated therapeutic pressure waveform by setting the operating parameters of the dynamic aspiration system 20 (e.g., by performing an inverse transform of the spectral analysis), including the baseline vacuum pressure applied by the vacuum source 24 to the aspiration catheter 22 and the characteristics of the pressure waveform (e.g., magnitude, frequency, shape, duty cycle, complexity, etc.), to achieve optimal performance for a given clinical scenario and given characteristics of the aspiration catheter 22. Alternatively, the aspiration modulation device 30 may select a modulated therapeutic pressure waveform from a library or look-up table of modulated therapeutic pressure waveforms respectively corresponding to different types of aspiration catheters. That is, the aspiration modulation device 30 may match the specific aspiration catheter 22 to one of the types of aspiration catheters stored in the library or look-up table, and select the modulated therapeutic pressure waveform corresponding to the matched type of aspiration catheter.

[48] In one example, the vessel in which the thrombus is located may be a middle cerebral artery (MCA) or an internal carotid artery (ICA), which may require different modulation frequencies and/or amplitudes to efficaciously and safely ingest the thrombus. For example, it may not be desirable to move the aspiration catheter 22 too much during an aspiration procedure when ingesting a thrombus in the MCA, and thus, lower frequency and/or lower amplitude modulation of the base vacuum pressure may be desirable to prevent damage to the MCA. In this case, the aspiration modulation device 30 may automatically set the frequency and/or amplitude modulation of the base vacuum pressure (e.g., by customizing or selecting a modulated pressure waveform) to a relatively low level in response to receiving clinical information indicating that the thrombus is located in the MCA. In contrast, since the ICA is a relatively large artery, it may be desirable to modulate the base vacuum pressure at a higher frequency and/or higher amplitude to maximize the efficiency of thrombus ingestion. In this case, the aspiration device 30 may automatically set the frequency and/or amplitude modulation of the base vacuum pressure to a relatively high level in response to receiving clinical information indicating that the thrombus is located in the ICA. In this case, the aspiration modulation device 30 may automatically set the frequency and/or amplitude modulation of the base vacuum pressure (e.g., by customizing or selecting a modulated pressure waveform) to a relatively high level in response to receiving clinical information indicating that the thrombus is located in the ICA. The modulation characteristics of the baseline vacuum pressure set by the aspiration modulation device 30 may also depend on the size of the aspiration catheter 22 relative to the size of the vessel in which the thrombus is located.

[49] In the embodiment illustrated in Fig. 3, the aspiration modulation device 30 generally comprises a user/data input device (e.g., a user interface (III)) 42, a controller/processor 44, a pressure manifold 46, a sensor 48, a fluid pressure oscillator 50, a fluid refill control element 52, and a vacuum flow control element 54.

[50] The III 42 can take the form of a control panel (e.g., with a display, buttons, keypad, touchscreen, microphone configured to receive voice commands, or the like) and provides user input to the controller/processor 44 for toggling the aspiration modulation device 30 on and off, providing the afore-described clinical scenario information to facilitate calibration of the dynamic aspiration system 20, changing the operational mode of the dynamic aspiration system 20 (e.g., a calibration mode, a dynamic mode (active modulation of the baseline vacuum pressure), a static vacuum mode (no modulation of the baseline vacuum pressure), and a diagnostic mode), selection of different desired modulated therapeutic pressure waveforms, etc. (e.g., via selection or adjustment of a modulation frequency or selection from a plurality of different modulated therapeutic pressure waveforms previously stored in memory (not shown) (e.g., in library or look-up table). The Ul 42 may optionally provide status/warning information using lights or sounds to signal modes, settings, events, operational mode, free-flow aspiration, active clot ingestion, plugged catheter, high/low pressure, clot type/modulus, diagnostic data, patient data, etc.

[51] The controller/processor 44 provides power and logistical control to the aspiration modulation device 30 and may take the form of, e.g., a microcontroller, for receiving input from the III 42 and controlling the fluid pressure oscillator 50 (described in further detail below) in accordance with the user input (e.g., changing operational modes or selecting modulated pressure waveforms). The controller/processor 44 is configured for, in response to the measured fluid pressure at the distal end 38 of the aspiration catheter 22 or the measured fluid pressure within the pressure manifold 46, dynamically modifying a waveform signal corresponding to a modulated therapeutic pressure waveform, and outputting the dynamically modified waveform signal. Such dynamic modification of the waveform signal facilitates tracking of the fluid pressure at the distal end 38 of the aspiration catheter 22 to the desired modulated pressure waveform. The desired modulated pressure waveform may be arbitrary in that any conceivable modulated pressure waveform (including the modulated complex therapeutic pressure waveform 110 illustrated in Fig. 5) may be envisioned.

[52] The controller/processor 44 may select such modulated therapeutic pressure waveform from a plurality of different modulated therapeutic pressure waveforms (e.g., stored in a library or look-up table), or the controller/processor 44 may customize such modulated therapeutic pressure waveform. The controller/processor 44 may communicate with the fluid pressure oscillator 50 either through a wired connection or a wireless connection. The controller/processor 44 may optionally comprise a battery (not shown).

[53] The controller/processor 44 may also be configured for analyzing or interpreting pressure data derived from the parameter measured by the sensor 48 when performing the diagnostic procedure described above, and generating or selecting a desired modulated therapeutic pressure waveform. In particular, the controller/processor 44 is configured for generating a plurality of waveform signals respectively corresponding to a plurality of different modulated diagnostic pressure waveforms (e.g., having different frequencies). As will be described in further detail, the fluid pressure oscillator modulates the baseline vacuum pressure in accordance with the waveform signals. The controller/processor 44 is further configured for analyzing the measured parameter in response to the modulation of the baseline vacuum pressure, and generating or selecting the modulated therapeutic pressure waveform based on the analysis of the measured fluid parameter. The controller/processor 44 may implement any of the in situ or apriori diagnostic procedures discussed above.

[54] For example, the controller/processor 44, in response to a thrombus that clogs the aspiration catheter 22, is configured for generating the plurality of waveform signals, determining one or more characteristics of the thrombus based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined characteristic(s) of the thrombus. As another example, the controller/processor 44 may generate a modulated therapeutic waveform or may select a modulated therapeutic waveform from a library or look-up table of modulated therapeutic waveforms based on a calibration of the aspiration catheter 22. In particular, the controller/processor 44, when the aspiration catheter 22 is connected to the aspiration modulation device 30, is configured for generating the plurality of waveform signals, determining a type of the aspiration catheter 22 based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined type of the aspiration catheter 22.

[55] The pressure manifold 46 comprises a manifold cavity 56, a vacuum inlet 58 configured for fluidly coupling the aspiration catheter 22 to a pressure chamber (described in further detail below) of the manifold cavity 56, and a vacuum outlet 60 configured for fluidly coupling the vacuum source 24 (via the aspirate collection container 28) to the manifold cavity 56, thereby allowing the vacuum source 24 to apply a baseline vacuum pressure to the aspiration catheter 22. The pressure manifold 46 further com prises a vent inlet 62 configured for fluidly coupling the pressurized fluid source 26 to the manifold cavity 56. The pressure manifold 46 may be coupled to the aspiration catheter 22, vacuum source 24, and pressurized fluid source 26 via the use of connectors (not shown) or may alternatively be integrated with the aspiration catheter 22, vacuum source 24, and pressurized fluid source 26 without the use of connectors.

[56] The fluid pressure oscillator 50 is configured for oscillating a variable volume of pressure modulating fluid (described in further detail below) within the manifold cavity 56 (i.e., alternately increasing and decreasing the variable volume of pressure modulating fluid) within the manifold cavity 56, which as a result, modulates the baseline vacuum pressure (i.e., the fluid pressure in the manifold cavity 56 oscillates around the baseline vacuum pressure). That is, increasing the variable volume of pressure modulating fluid in the manifold cavity 56 via the fluid pressure oscillator 50 correspondingly decreases the pressure in the manifold cavity 56, while decreasing the variable volume of pressure modulating fluid in the manifold cavity 56 via the fluid pressure oscillator 50 correspondingly increases the pressure in the manifold cavity 56. The variable volume of pressure modulating fluid within the manifold cavity 56 may be alternately increased and decreased in a global manner, such the fluid pressure alternately falls below and rises above the baseline vacuum pressure (e.g., to create the rectangular components 112 and sinusoidal components 114 of the therapeutic pressure waveform 1 10 illustrated in Fig. 6), or in a local manner, such that the fluid pressure alternatively increases and decreases, but remains below the baseline vacuum pressure or remains above the baseline vacuum pressure (e.g., to create the cut-sine or sawtooth components 116 of the therapeutic pressure waveform 110 illustrated in Fig. 5)

[57] As will be described in further detail below, the fluid pressure oscillator 50 modulates a vacuum pressure within the manifold cavity 56 in accordance with the waveform signal that has been dynamically modified by the controller/processor 44 in response to the parameter measured by the sensor 48 (indicative of the fluid pressure at the distal end 38 of the aspiration catheter 22), such that fluid pressure measured by the sensor 48 tracks the desired modulated pressure waveform; or alternatively, in accordance with a plurality of waveform signals corresponding to a plurality of different modulated diagnostic pressure waveform signals.

[58] In the illustrated embodiment, the fluid pressure oscillator 50 comprises a pressure transduction element 66, an actuator 68, and a driver 70. The pressure transduction element 66 directly interfaces with the pressure modulating fluid within the manifold cavity 56 (and in particular, within a pressure chamber of the manifold cavity 56, as will be discussed in further detail below), and is configured for being physically moved to oscillate such variable volume of pressure modulating fluid, thereby converting mechanical energy into fluid energy. The actuator 68 is configured for being operably coupled to the pressure transduction element 66, and in particular, is configured for physically moving the pressure transduction element 66 in an oscillatory manner. As will be described in further detail below, the pressure transduction element 66 may advantageously comprise a movable manifold boundary (such as, e.g., a diaphragm) affixed within the manifold cavity 56, while the actuator may comprise, e.g., voice coil actuator, motor, rotary to linear cam, solenoid, audio exciter, peristaltic pump, rotary vane, gear, screw, syringe, pneumatic piston, pneumatic pulse generator, etc.

[59] The driver 70 is configured for controlling the actuator 68 in accordance with the modulated pressure waveform signal customized by the controller/processor 44 or selected by the controller/processor 44 (e.g., from a library or look-up table or in accordance with a selection made by the user (e.g., by varying or selecting a parameter (e.g., modulation frequency) of the modulated pressure waveform) to physically move the pressure transduction element 66 in a manner that oscillates the variable volume of the pressure modulating fluid within the manifold cavity 56, thereby modulating the vacuum pressure within the manifold cavity 56.

[60] In one embodiment, the driver 70 is electrical in nature (i.e. , the driver 70 electrically drives the actuator 68 (e.g. , if the actuator 68 takes the form of a voice coil), although in alternative embodiments, the driver 70 may drive the actuator 68 using other forms of energy, including electromagnetic, pneumatic, hydraulic, etc. The driver 70 may comprise a waveform generator and actuator controller capable of controlling the fluid pressure oscillator 50 in a very precise manner, such that the fluid pressure measured by the sensor 48 tracks the desired modulated pressure waveform.

[61] Although the control ler/processor 44 and driver 70 are described herein as being separate components, it should be appreciated that portions or all functionality of the controller/processor 44 and driver 70 may be performed by a single component. Furthermore, although all of the functionality of the controller/processor44 is described herein as being performed by a single component, and likewise all of the functionality of the driver 70 is described herein as being performed by a single component, such functionality of each of the controller/processor 44 and driver 70 may be distributed amongst several components. For example, the control functions may be performed by a separate controller, while the processing functions may be performed by a separate processor. It should be appreciated that those skilled in the art are familiar with the terms “controller,” “processor,” and “driver,” and that they may be implemented in software, firmware, hardware, or any suitable combination thereof.

[62] The sensor 48 is configured for measuring a fluid pressure indicative of the fluid pressure at the distal end 38 of the catheter body 32 to provide fluid pressure feedback to the driver 70, such that the fluid pressure in the manifold cavity 56 may be directly controlled. Furthermore, because the fluid pressure in the manifold cavity 56 is directly controlled, the actuator 68 may utilize pure open loop position control. Optionally, one or more actuator sensors (e.g., position feedback sensors) 72 may be initially employed to calibrate the actuator 68 (e.g., to determine the midpoint and upper and lower limits of the actuator 68), and then turned off after such calibration, after which open loop position control of the actuator 68, which enables a higher level of precision of the actuator 68 at higher frequencies, may be utilized. [63] In one embodiment, the sensor 48 is a pressure sensor located in the distal end 38 of the catheter body 32, such that the fluid pressure in the distal end 38 of the catheter body 32 can be directly measured, or may be a pressure sensor located in the manifold cavity 56 or even in the fluid pressure oscillator 50, such that the fluid pressure in the distal end 38 of the catheter body 32 can be indirectly measured or inferred from the fluid pressure measurements in the manifold cavity 56 or fluid pressure oscillator 50. Alternatively, the sensor 48 may be a force feedback sensor that measures the output force of the actuator 68.

[64] The fluid pressure in the fluid pressure oscillator 50 (e.g., in the manifold cavity 56), and thus by implication the fluid pressure at the distal end 38 of the catheter body 32, can be inferred based on the size of the actuator 68. For example, the fluid pressure in the manifold cavity 56 may be computed (e.g., by the control ler/processor 44) based on the measured force (e.g., by dividing the measured force by a known area of the actuator 68 acting on the fluid pressure oscillator 50).

[65] In one advantageous embodiment, the actuator 68 has an input ted by the driver 70 that is directly proportional to the output force of the actuator 68, and thus, the fluid pressure within the distal end 38 of the catheter body 32. In this case, the sensor 48 may take the form of a circuit that measures the magnitude of the electrical input (e.g., a current sensing circuit), thereby obviating the need for a separate sensor in the catheter body 32 or the manifold cavity 56.

[66] Significantly, the employment of a sensor 48 that measures fluid pressure that is indicative of the fluid pressure at the distal end 38 of the catheter body 32 allows the fluid pressure oscillator 50 to more precisely generate the desired pressure waveform at the distal end 38 of the catheter body 32, as discussed above. In an optional embodiment, the sensor 48 or another sensor may be employed to generate a fluid pressure profile that can be analyzed (e.g., by the driver 70) to sense system leaks, air plugs, siphon interruptions, pressure loss, and other issues.

[67] The fluid refill control element 52 is configured for selectively fluidly coupling the pressurized fluid source 26 via the vent inlet 62 to the manifold cavity 56 to maintain the working volume of pressure modulating fluid (or fluid pressure) within the manifold cavity 56 at a desired mean value, and thus, a desired mean fluid pressure within the manifold cavity 56. In particular, although fluid will enter the manifold cavity 56 via the vacuum inlet 58 and exit the manifold cavity 56 via the vacuum outlet 60, the amount of fluid exiting the manifold cavity 56 may be greater than the fluid entering the manifold cavity 56, thereby reducing the average fluid volume of, and thus the fluid pressure within, the manifold cavity 56, due to excess fluid withdrawal from the manifold cavity 56. However, the fluid refill control element 52 periodically or continuously injects small amounts of pressure modulating fluid from the pressurized fluid source 26 into the manifold cavity 56 via the vent inlet 62 to maintain a desired mean volume of pressure modulating fluid, and thus the desired mean fluid pressure within, the manifold cavity 56.

[68] In the illustrated embodiment, the fluid refill control element 52 comprises a check valve in fluid communication between the pressurized fluid source 26 and the vent inlet 62, such that, when a fluid pressure within the manifold cavity 56 drops below a threshold fluid pressure (and in this case, the fluid pressure of the pressurized fluid source 26), the check valve opens, thereby allowing pressure modulating fluid to be conveyed from the pressurized fluid source 26 into the manifold cavity 56. In this manner, the average designed fluid pressure in the manifold cavity 56 may be maintained despite the loss of blood/fluid out of the vacuum outlet 60 and into the aspirate collection container 28. When the fluid pressure within the manifold cavity 56 rises above a fluid pressure of the pressurized fluid source 26, the check valve closes, thereby preventing fluid from being conveyed from the manifold cavity 56 into the pressurized fluid source 26.

[69] Because the fluid refill control element 52 only fluidly couples the pressurized fluid source 26 to the manifold cavity 56 when necessary (i.e., it is designed to only occasionally bleed in saline to the manifold cavity 56), the amount of saline that ends up in the aspirate collection container 28 will be minimal, thereby allowing the nature and amount of tissue removed from the patient to be more easily determined.

[70] Furthermore, the fluid refill control element 52 may be designed to provide a low pressure safety limit by opening in response to the fluid pressure within the manifold cavity 56 dropping below a specific fluid pressure. As such, the fluid refill control element 52 serves to provide the aspiration modulation device 30 with a low pressure safety limit by preventing the fluid pressure within the manifold cavity 56 from dropping below a particular fluid pressure value. In one embodiment, the fluid refill control element 52 may also incorporate a feedback sensor/control (not shown) for the pressure in the manifold cavity 56 by checking the pressure when the pressure transduction element 66 is in its midpoint/average/neutral position to determine whether the pressure is at a pre-defined setpoint pressure for that position of the actuator 68. In this manner, the position of the actuator 68 is more closely tied to the actual pressure within the manifold cavity 56.

[71] In an optional embodiment, the fluid refill control element 52 comprises a constant pressure system (not shown) that can be used to provide consistent pressure to the manifold cavity 56 via passive or active pressure regulation means, such as a pressure regulator, or a pressure bladder or pressure bubble, to eliminate system performance discrepancies among different facilities located at different altitudes, and thus, having different absolute atmospheric pressures. Thus, the constant pressure system enables the fluid refill control element 52 to supply a constant atmosphere- pressure-equivalized pressure modulating fluid to the manifold cavity 56, thereby enabling the fluid pressure oscillator 50 to precisely generate the desired modulated pressure waveform that is essential to the effectiveness of the aspiration.

[72] The vacuum flow control element 54 is configured for preventing backflow of blood/fluid from the aspirate collection container 28 into the manifold cavity 56. For example, the vacuum flow control element 54 may comprise minimal flow restriction one-way valve in fluid communication between the aspirate collection container 28 and the vacuum outlet 60, such that, when a fluid pressure within the pressure manifold 46 drops below the baseline vacuum pressure (e.g., during the valleys of the therapeutic pressure waveform 110 illustrated in Fig. 5), the one-way valve closes, thereby preventing fluid/blood from being conveyed from the aspirate collection container 28 into the manifold cavity 56.

[73] In an optional embodiment, the aspiration modulation device 30 further comprises one or more over-pressure relief valves (not shown) configured for releasing pressure from the manifold cavity 56 if the fluid pressure within the manifold cavity 56 exceeds a maximum threshold limit. In another optional embodiment, the aspiration modulation device 30 further includes a means for regulating the baseline vacuum pressure (not shown) at the desired baseline vacuum pressure. In still another optional embodiment, the aspiration modulation device 30 further comprises a barometric pressure sensor (not shown) configured for measuring the local barometric pressure (e.g., due to altitude changes or transient weather conditions), such that the vacuum source 24 may accordingly adjust the baseline vacuum pressure relative to the barometric pressure to maintain a desired pressure differential between the baseline vacuum pressure and the measured barometric pressure. In still another optional embodiment, the aspiration modulation device 30 further includes a means for regulating the baseline vacuum pressure (not shown) at the desired baseline vacuum pressure.

[74] Referring now to Figs. 7A-7C, one specific embodiment of an aspiration modulation device 30a will be described. The aspiration modulation device 30a comprises a single casing or housing 72 carrying the controller/processor 44 and a fluid pressure oscillator 50a. In the illustrated embodiment, the casing 72 is a two-part casing that comprises a top casing portion 72a and a bottom casing portion 72b that are removably coupled to each other to facilitate reuse of a portion of the aspiration modulation device 30a, as will be discussed in further detail below. The controller/processor 44 and driver 70 are contained within the top casing portion 72a, while the Ul 42 is affixed to the exterior of the top casing portion 72a. The bottom casing portion 72b, at least in part, forms the pressure manifold 46, with the manifold cavity 56 being formed within the bottom casing portion 72b, and the vacuum inlet 58 (which may take the form of a male luer lock fitting), vacuum outlet 60 (which may take the form of a female luer lock fitting) along with the vacuum flow control element 54, and vent inlet 62 (which may take the form of a female luer lock fitting) along with the fluid refill control element 52, being affixed to the bottom casing portion 72b in fluid communication with the manifold cavity 56. The sensor 48 is affixed to the bottom casing portion 72b in fluid communication with the manifold cavity 56.

[75] Because the control functions are performed by the componentry in the top casing portion 72a, and the working functions are performed by the componentry in the bottom casing portion 72b, the top casing portion 72a may be considered a master unit, while the bottom casing portion 72b may be considered a slave unit. Other embodiments of master and slave units will be discussed further below.

[76] In the embodiment illustrated in Figs. 7A-7C, the fluid pressure oscillator 50a takes the form of a direct drive diaphragm assembly. In particular, the fluid pressure oscillator 50a comprises a pressure transduction element 66a that takes the form of a movable manifold boundary (and in particular a diaphragm) that divides the manifold cavity 56 between a pressure chamber 56a containing a variable volume of pressure modulating fluid 74 in fluid communication with the vacuum inlet 58, vacuum outlet 60, and vent inlet 62, and a working chamber 56b that is fluidly isolated from the vacuum inlet 58, vacuum outlet 60, and vent inlet 62. The pressure chamber 56a of the manifold cavity 56 is bounded by a bottom wall 76 and sidewall 78 of the bottom casing portion 72b and the opposing diaphragm 66a. Thus, it can be appreciated that the diaphragm 66a sterilely seals the working chamber 56b of the manifold cavity 56 from the pressure modulating fluid 74 contained in the pressure chamber 56a of the manifold cavity 56, thereby preventing cross-contamination between the pressure chamber 56a and the working chamber 56b.

[77] The fluid pressure oscillator 50a further comprises a linear actuator 68a comprising an actuator housing 80 (e.g., a voice coil) and a rod 82 directly mechanically coupled to the diaphragm 66a via a coupling 84, such that the diaphragm 66a may be alternately flexed from a nominal state of flex away from the actuator housing 80 and towards the bottom wall 76 of the casing 72 to reciprocatably oscillate the variable volume of pressure modulating fluid 74, and thus the fluid pressure within, the manifold cavity 56. The actuator housing 80 is contained within the top casing portion 72a, while the rod 82 is disposed in the bottom casing portion 72b.

[78] As illustrated in Fig. 7A, the rod 82 is in a nominal position relative to the actuator housing 80, such that the diaphragm 66a is in a nominal flex state relative to the relative to the bottom wall 76 of the casing 72, and the pressure chamber 56a has a nominal volume of pressure modulating fluid 74 at a nominal fluid pressure (in this case, at the baseline vacuum pressure). As illustrated in Fig. 7B, when the rod 82 is linearly translated from its nominal position away from the actuator housing 80 (downward as shown by the arrow), the diaphragm 66a is flexed from its nominal flex state towards the bottom wall 76 of the casing 72, thereby decreasing the volume of pressure modulating fluid 74, and thus correspondingly increasing the fluid pressure from the baseline vacuum pressure, in the pressure chamber 56a. In contrast, as illustrated in Fig. 7C, when the rod 82 is linearly translated from its nominal position towards the actuator housing 80 (upward as shown by the arrow), the diaphragm 66a is flexed from its nominal flex state away the bottom wall 76 of the casing 72, thereby increasing the volume of pressure modulating fluid 74, and thus correspondingly decreasing the fluid pressure from the baseline vacuum pressure, in the pressure chamber 56a.

[79] Although the nominal position of the rod 82 is illustrated as being centered between its maximum and minimum linear translations, such that the baseline vacuum pressure applied by the vacuum source 24 to the pressure chamber 56a is modulated in accordance with the therapeutic pressure waveform 110 illustrated in Fig. 6 (i.e., the average pressure in the pressure chamber 56a is equal to such baseline vacuum pressure), the nominal position of the rod 82 may be off-center relative to the maximum and minimum linear translations, such that a vacuum pressure different from the baseline vacuum pressure applied by the vacuum source 24 to the pressure chamber 56a is modulated.

[80] In one advantageous embodiment, the coupling 84 removably couples the rod 82 to the diaphragm 66a, such that the actuator 68a, including the rod 82, may be easily decoupled from the diaphragm 66a. For example, the coupling 84 can be a screw, clasp mechanism, slotted insert coupling, snapped fitting, pinned union, magnetic holding, threaded union, or any other mechanism that can be quickly manipulated to decouple the rod 82 of the actuator 68a from the diaphragm 66a. As discussed above, the top casing portion 72a carries the more expensive components (in this case, the electronics) of the aspiration modulation device 30a, including the Ul 42, controller/processor 44, actuator 68a, and driver 70, while the bottom casing portion 72b carries the less expensive components (in this case, passive components), including the diaphragm 66a, the vacuum inlet 58, vacuum outlet 60 (along with the vacuum flow control element 54), and vent inlet 62 (along with the fluid refill control element 52).

[81] Because the bottom casing portion 72b is removably coupled to the top casing portion 72a, while the rod 82 of the actuator 68a is removably coupled to the diaphragm 66a, the top casing portion 72a, along with its contents, can be made to be reusable, while the bottom casing portion 72b, along with its contents, can be made to be disposable. That is, after use, the bottom casing portion 72b, including the diaphragm 66a, vacuum inlet 58 (and vacuum flow control element 54), the vacuum outlet 60, and vent inlet 62 (and fluid refill control element 52), can be removed from the top casing portion 72a and discarded, and replaced with a new bottom casing portion 72b, including a new diaphragm 66a, vacuum inlet 58 (and vacuum flow control element 54), vacuum outlet 60, and vent inlet 62 (and fluid refill control element 52), for subsequent use.

[82] Alternatively, the bottom casing portion 72b, including its contents, can be removed from the top casing portion 72a, re-sterilized, and re-affixed to the top casing portion 72a. In this manner, the top casing portion 72a, along with the more sensitive electronic components (which have been sterilely isolated from the pressure modulating fluid 74 contained in the sterile bottom casing portion 72b via the diaphragm 66a) need not be sterilized, thereby preventing thermal damage to the electronic components and/or obviating the need to design more expensive electronic componentry that can withstand one or more thermal cycles used during a typical sterilization procedure.

[83] Referring now to Figs. 8A-8C, another specific embodiment of an aspiration modulation device 30b will be described. The aspiration modulation device 30b is similar to the modulation device 30a described above with respect to Figs. 7A-7C, with the exception that the aspiration modulation device 30b comprises a fluid pressure oscillator 50b that takes the form of an indirect drive diaphragm assembly.

[84] In particular, the fluid pressure oscillator 50b comprises a primary pressure transduction element 66b that takes the form of a piston, and a secondary pressure transduction element 66c that takes the form of a movable manifold boundary (and in particular a diaphragm). The manifold cavity 56 (in this case, the top casing portion 72a) comprises an upper reduced diameter cylinder 86 in which the piston 66b reciprocatably moves. The manifold cavity 56 (in this case, the bottom casing portion 72b) comprises a lower increased diameter cylinder 88 in which the diaphragm 66c is affixed, such that the lower increased diameter cylinder 88 is divided between a pressure chamber 56a containing a variable volume of secondary pressure modulating fluid 74” in fluid communication with the vacuum outlet 60, vacuum inlet 58, and vent inlet 62, and a working chamber 56b containing primary pressure modulating fluid 74’ fluidly isolated from the vacuum outlet 60, vacuum inlet 58, and vent inlet 62. Thus, it can be appreciated that the diaphragm 66c sterilely seals the primary pressure modulating fluid 74’ contained in the working chamber 56b of the manifold cavity 56 from the secondary pressure modulating fluid 74” contained in the pressure chamber 56a of the manifold cavity 56, thereby preventing cross-contamination between the pressure chamber 56a and the working chamber 56b.

[85] The aspiration modulation device 30b further comprises an actuator 68b that comprises the previously mentioned actuator housing 80 (e.g., a voice coil), and a piston shaft 90 mechanically coupling the piston 66b to the actuator housing 80. The actuator housing 80, piston shaft 90, and piston 66b are contained within the top casing portion 72a. The piston 66b is fluidly coupled to the diaphragm 66c via the primary pressure modulating fluid 74’ contained within the working chamber 56b of the lower increased diameter cylinder 88. Thus, by reciprocatably moving the piston 66b from its nominal position toward and away from the diaphragm 66c, the volume of primary pressure modulating fluid 74’, and thus the fluid pressure within, the working chamber 56b may be reciprocatably oscillated, thereby reciprocatably flexing the diaphragm 66c from its nominal flex state towards and away from the bottom wall 76 of the bottom casing portion 72b to reciprocatably oscillate the volume of secondary pressure modulating fluid 74”, and thus the fluid pressure within the working chamber 56b. Notably, the arrangement of the piston 66b (i.e., the primary pressure transduction element) within the upper reduced diameter cylinder 86 and the diaphragm 66c within the lower increased diameter cylinder 88 provides an indirect force amplification between the piston 66b and the diaphragm 66c. It should be appreciated that, although indirect force amplification is performed by hydraulic means in the aspiration modulation device 30b, the force amplification can be performed, either directly or indirectly, using other means, including pneumatically or mechanically.

[86] As illustrated in Fig. 8A, the piston shaft 90 is in a nominal position relative to the actuator housing 80, such that the piston 66b is in a nominal position relative to the upper reduced diameter cylinder 86, and the working chamber 56b has a nominal volume of primary pressure modulating fluid 74’, such that the diaphragm 66c is in a nominal flex state relative to the bottom wall 76 of the casing 72, and the pressure chamber 56a has a nominal volume of secondary pressure modulating fluid 74” at a nominal pressure (in this case, at the baseline vacuum pressure).

[87] As illustrated in Fig. 8B, when the piston shaft 90 is linearly translated from its nominal position away from the actuator housing 80 (downward as shown by the arrow), the piston 66b is linearly translated from its nominal position toward the diaphragm 66c, thereby decreasing the volume, and thus increasing pressure, of the primary pressure modulating fluid 74’ within the working chamber 56b. In turn, the increased pressure of the primary pressure modulating fluid 74’ within the working chamber 56b of the lower increased diameter cylinder 88 flexes the diaphragm 66c from its nominal flex state towards the bottom wall 76 of the casing 72, thereby decreasing the variable volume of secondary pressure modulating fluid 74” in the pressure chamber 56a, and thus correspondingly increasing the fluid pressure from the baseline vacuum pressure in the pressure chamber 56a.

[88] In contrast, as illustrated in Fig. 8C, when the piston shaft 90 is linearly translated from its nominal position toward the actuator housing 80 (upward as shown by the arrow), the piston 66b is linearly translated from its nominal position away the diaphragm 66c, thereby increasing the volume, and thus decreasing pressure, of the primary pressure modulating fluid 74’ within the working chamber 56b. In turn, the decreased pressure of the primary pressure modulating fluid 74’ within the working chamber 56b flexes the diaphragm 66c from its nominal flex state away from the bottom wall 76 of the casing 72, thereby increasing the variable volume of the secondary pressure modulating fluid 74” in the pressure chamber 56a, and thus correspondingly decreasing the fluid pressure from the baseline vacuum pressure in the pressure chamber 56a.

[89] In the same manner described above with respect to the aspiration modulation device 30a of Figs. 7A-7C, the bottom casing portion 72b is removably coupled to the top casing portion 72a. However, in this case, there is no mechanical coupling between the actuator 68b and the diaphragm 66c. Thus, after use, the bottom casing portion 72b, including the diaphragm 66c and the vacuum inlet 58 (and vacuum flow control element 54), vacuum outlet 60, and vent inlet 62 (and fluid refill control element 52), can be removed from the top casing portion 72a and discarded. The top casing portion 72a, including its contents, can thus be made to be reusable by replacing the discarded bottom casing portion 72b and replaced with a new bottom casing portion 72b, including a new diaphragm 66c, vacuum inlet 58 (and vacuum flow control element 54), vacuum outlet 60, and vent inlet 62 (and fluid refill control element 52), for subsequent use. Alternatively, the bottom casing portion 72b, including its contents, can be removed from the top casing portion 72a, re-sterilized, and re-affixed to the top casing portion 72a. In this manner, the top casing portion 72a, along with the more sensitive electronic components (which have been sterilely isolated from the secondary pressure modulating fluid 74” contained in the sterile bottom casing portion 72b via the diaphragm 66c need not be sterilized, thereby preventing thermal damage to the electronic components and/or obviating the need to design more expensive electronic componentry that can withstand one or more thermal cycles used during a typical sterilization procedure.

[90] In an alternative embodiment, the actuator may take the form of a pneumatic or hydraulic actuator. For example, the actuator may take the form of a valve system comprising a high pressure valve (not shown) and a low pressure valve (not shown) in fluid communication with the working chamber of the manifold cavity. The high and low pressure valves may be selectively opened and closed to alternately pressurize and depressurize the working chamber, thereby alternately flexing the diaphragm towards and away from the bottom wall of the casing to alternately decrease and increase the variable volume of pressure modulating fluid in the pressure chamber, thus correspondingly increasing and decreasing the fluid pressure from the baseline vacuum pressure in the pressure chamber.

[91] Referring now to Figs. 9A-9G, still another specific embodiment of an aspiration modulation device 30c will be described. The aspiration modulation device 30c is similar to the modulation device 30a described above with respect to Figs. 7A- 7C, with the exception that, instead of comprising a single fluid pressure oscillator 50a, the aspiration modulation device 30c comprises a pair of fluid pressure oscillators 50a’, 50a”. The fluid pressure oscillators 50a’, 50a” respectively comprise a pair of pressure transduction elements 66a’, 66a” (and in this case, a pair of opposing diaphragms), a pair of actuators 68a’, 68a”, and a pair of drivers 70’, 70” that are respectively identical to the pressure transduction element 66a, actuator 68a, and driver 70 illustrated in Figs. 7A-7C.

[92] The casing 72 is a three-part casing that comprises a top casing portion 72a, a bottom casing portion 72b, and a central casing portion 72c that are removably coupled to each other. The controller/processor 44, driver 70’, and actuator housing 80 of the actuator 68a’ are contained within the top casing portion 72a, while the rod 82 of the actuator 68a’ is contained within the central casing portion 72c. Likewise, the driver 70” and actuator housing 80 of the actuator 68a” are contained within the bottom casing portion 72b, while the rod 82 of the actuator 68a’ is contained within the central casing portion 72c. In the illustrated embodiment, the controller/processor 44 is contained within the top casing portion 72a, and the III 42 (not shown) is affixed to the exterior of the top casing portion 72a, although in alternative embodiments, the controller/processor 44 (or any portion thereof) may be contained within the bottom casing portion 72b and the Ul 42 may be affixed to the exterior of the bottom casing portion 72b.

[93] The central casing portion 72c, at least in part, forms the pressure manifold 46, with the manifold cavity 56 being formed within the central casing portion 72c, and the vacuum inlet 58, vacuum outlet 60 along with the vacuum flow control element 54, and vent inlet 62 along with the fluid refill control element 52, being affixed to the central casing portion 72c in fluid communication with the manifold cavity 56. A pressure chamber 56a of the manifold cavity 56 that contains the variable volume of pressure modulating fluid 74 in fluid communication with the vacuum outlet 60, vacuum inlet 58, and vent inlet 62 is formed between the opposing diaphragms 66a’, 66a”, whereas the working chambers 56b of the manifold cavity 56 that are fluidly isolated from the vacuum outlet 60, vacuum inlet 58, and vent inlet 62 are formed outside of the opposing diaphragms 66a’, 66a”. The pressure chamber 56a of the manifold cavity 56 is bounded by side wall 78 of the central casing portion 72c and the opposing diaphragms 66a’, 66a”. Thus, it can be appreciated that the diaphragms 66a’, 66a” sterilely seal the working chambers 56b of the manifold cavity 56 from the pressure modulating fluid 74 contained in the pressure chamber 56a of the manifold cavity 56, thereby preventing cross-contamination between the pressure chamber 56a and the working chambers 56b.

[94] In the same manner discussed above with respect to the actuator 68a of the aspiration modulation device 30a illustrated in Figs. 7A-7C, each of the actuators 68a’, 68a” is a linear actuator comprising an actuator housing 80 (e.g., a voice coil) and a rod 82 directly mechanically coupled to the respective diaphragm 66a’, 66a” via a coupling 84. In this manner, the variable fluid volume of the manifold cavity 56 may be reciprocatably oscillated concurrent, but independently, by the diaphragms 66a’, 66a”. That is, the diaphragms 66a’, 66a” may be translated relative to each other in any arbitrary position.

[95] For example, as illustrated in Fig. 9A, both rods 82 are in nominal positions relative to the actuator housings 80 of the respective actuators 68a’, 68a”, such that the diaphragms 66a’, 66a” are in a state of flex relative to each other, and the pressure chamber 56a has a nominal fluid volume at a nominal pressure (in this case, at the baseline vacuum pressure).

[96] As illustrated in Fig. 9B, when the rod 82 of the first actuator 68a’ is linearly translated from its nominal position away from the actuator housing 80 of the first actuator 68a’ (downward as shown by the arrow), while the rod 82 of the second actuator 68a” remains at its nominal position relative to the actuator housing 80 of the second actuator 68a”, thereby flexing the diaphragm 66a’ toward the diaphragm 66a”, the variable volume of pressure modulating fluid 74 is decreased in the pressure chamber 56a of the manifold cavity 56, and thus the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is correspondingly increased from the baseline vacuum pressure.

[97] As illustrated in Fig. 9C, when the rod 82 of the second actuator 68a” is linearly translated from its nominal position away from the actuator housing 80 of the second actuator 68a” (upward as shown by the arrow), while the rod 82 of the first actuator 68a’ remains at its nominal position relative to the actuator housing 80 of the first actuator 68a’, thereby flexing the diaphragm 66a” toward the diaphragm 66a’, the variable volume of pressure modulating fluid 74 is decreased in the pressure chamber 56a of the manifold cavity 56, and thus the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is correspondingly increased from the baseline vacuum pressure.

[98] As illustrated in Fig. 9D, when the rod 82 of the first actuator 68a’ is linearly translated from its nominal position away from the actuator housing 80 of the first actuator 68a’ (downward as shown by the arrow), while the rod 82 of the second actuator 68a” is linearly translated from its nominal position away from the actuator housing 80 of the second actuator 68a (upward as shown by the arrow), thereby flexing the diaphragms 66a’, 66a” toward each other, the variable volume of pressure modulating fluid 74 is decreased in the pressure chamber 56a of the manifold cavity 56, and thus the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is correspondingly increased from the baseline vacuum pressure. It should be appreciated that, because both diaphragms 66a’ 66a” are flexed towards each other, the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is increased from the baseline vacuum pressure even greater than the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is increased in the arrangements of Figs. 9B-9C, where only one of the diagrams 66a’, 66a” is flexed towards the other one of the diagrams 66a’, 66a”.

[99] As illustrated in Fig. 9E, when the rod 82 of the first actuator 68a’ is linearly translated from its nominal position toward the actuator housing 80 of the first actuator 68a’ (upward as shown by the arrow), while the rod 82 of the second actuator 68a” remains at its nominal position relative to the actuator housing 80 of the second actuator 68a”, thereby flexing the diaphragm 66a’ away from the diaphragm 66a”, the variable volume of pressure modulating fluid 74 is increased in the pressure chamber 56a of the manifold cavity 56, and thus the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is correspondingly decreased from the baseline vacuum pressure.

[100] As illustrated in Fig. 9F, when the rod 82 of the second actuator 68a” is linearly translated from its nominal position toward the actuator housing 80 of the second actuator 68a” (downward as shown by the arrow), while the rod 82 of the first actuator 68a’ remains at its nominal position relative to the actuator housing 80 of the first actuator 68a’, thereby flexing the diaphragm 66a” away from the diaphragm 66a’, the variable volume of pressure modulating fluid 74 is increased in the pressure chamber 56a of the manifold cavity 56, and thus the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is correspondingly decreased from the baseline vacuum pressure.

[101] As illustrated in Fig. 9G, when the rod 82 of the first actuator 68a’ is linearly translated from its nominal position toward the actuator housing 80 of the first actuator 68a’ (upward as shown by the arrow), while the rod 82 of the second actuator 68a” is linearly translated from its nominal position toward the actuator housing 80 of the second actuator 68a (downward as shown by the arrow), thereby flexing the diaphragms 66a’, 66a” away from each other, the variable volume of pressure modulating fluid 74 is increased in the pressure chamber 56a of the manifold cavity 56, and thus the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is correspondingly decreased from the baseline vacuum pressure. It should be appreciated that, because both diaphragms 66a’ 66a” are flexed away from each other, the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is decreased from the baseline vacuum pressure even more than the fluid pressure in the pressure chamber 56a of the manifold cavity 56 is decreased in the arrangements of Figs. 9E-9F, where only one of the diagrams 66a’, 66a” is flexed away from the other one of the diagrams 66a’, 66a”.

[102] It should be appreciated, although only seven different combinations of flex states are illustrated in Figs. 9A-9G, the rods 82 of the actuators 68a’, 68a” may be linearly translated from their nominal positions to any position independent of each other, and thus, the diaphragms 66a’, 66a” of the actuators 68a’, 68a” may be flexed from their relative flex state to any arbitrary relative flex state. In this manner, the two fluid pressure oscillators 50a’, 50a” may generate more complex modulated pressure waveforms (e.g., by extending the range of pressure, providing additional stages of pressure amplitude, tailoring frequency components, providing additional fluctuation frequency components, etc.) that may otherwise only be performed by a single, more expensive high speed/acceleration/precision fluid pressure oscillator. That is, instead of requiring a single fluid pressure oscillator that generates the complex modulated pressure waveform, the complexity of the modulated pressure waveform is distributed between two fluid pressure oscillators that are acting in concert with each other, such that each fluid pressure oscillator has a less complicated sequence of motions required to generate the complex modulated pressure waveform. Thus, the combination of the two fluid pressure oscillators may not only be more dynamically robust in generating the complex modulated pressure waveform, the fluid pressure oscillators may comprise simpler, more cost-effective, actuators. Although the aspiration modulation device 30a is illustrated and described as comprising only two fluid pressure oscillators, it should be appreciated that alternative embodiments of aspiration modulation devices may have more than two fluid pressure oscillators to generate even more complex modulated pressure waveforms. The multiple fluid pressure oscillators of such aspiration modulation devices may be aligned in a linear array, a circle, a combination thereof (such as two pairs of fluid pressure oscillators in a line).

[103] Notably, in the same manner that the coupling 84 removably couples the rod 82 to the diaphragm 66a in the fluid pressure oscillator 50a illustrated in Figs. 7A- 7C, the rods 82 of the respective actuators 68a’, 68a” may be easily coupled from the diaphragms 66a’, 66a”. As discussed above, the top and bottom casing portions 72a, 72b contain the more expensive components (in this case, the electronics) of the aspiration modulation device 30c, including the III 42, control ler/processor 44, actuators 68a’, 68a”, and drivers 70’, 70”, while the central casing portion 72c contains the less expensive components (in this case, passive components), including the diaphragms 66a’, 66a”, the vacuum inlet 58, vacuum outlet 60 (along with the vacuum flow control element 54), and vent inlet 62 (along with the fluid refill control element 52). Because, the top and bottom casing portions 72a, 72b are removably coupled to the central casing portion 72c, while the rods 82 of the actuators 68a’, 68a” are removably coupled to the diaphragms 66a’, 66a”, the top and bottom casing portions 72a, 72b can be made to be reusable, while the central casing portion 72c, along with its contents, can be made to be disposable. That is, after use, the top and bottom casing portions 72a, 72b, including the diaphragms 66a’, 66a” and the vacuum inlet 58 (and vacuum flow control element 54), vacuum outlet 60, and vent inlet 62 (and fluid refill control element 52), can be removed from the central casing portion 72c and discarded, and replaced with new top and bottom casing portions 72a, 72b, including new diaphragms 66a’, 66a”, vacuum inlet 58 (and vacuum flow control element 54), vacuum outlet 60, and vent inlet 62 (and fluid refill control element 52), for subsequent use. Alternatively, the top and bottom casing portions 72a, 72b, including their contents, can be removed from the central casing portion 72c, re-sterilized, and re- affixed to the central casing portion 72c. In this manner, the top and bottom casing portions 72a, 72b, along with the more sensitive electronic components (which have been sterilely isolated from the pressure modulating fluid 74 contained in the sterile central casing portion 72c via the diaphragms 66a’, 66a”, need not be sterilized, thereby preventing thermal damage to the electronic components and/or obviating the need to design more expensive electronic componentry that can withstand one or more thermal cycles used during a typical sterilization procedure.

[104] Although the fluid pressure oscillators 50a’, 50a” are illustrated and described as comprising a pair of pressure transduction elements 66a’, 66a” (and in this case, a pair of opposing diaphragms) and a pair of actuators 68a’, 68a” that are respectively identical to the pressure transduction element 66a and actuator 68a illustrated in Figs. 7A-7C, it should be appreciated that one or both of the fluid pressure oscillators of alternative embodiments of an aspiration modulation device may be different from that illustrated in Figs. 9A-9M. For example, instead of having a direct drive diaphragm assembly, one or both of the fluid pressure oscillators may have an indirect drive diaphragm assembly, such as that illustrated in Figs. 8A-8C, or any other diaphragm-based assembly sufficient to oscillate the variable fluid volume of the manifold cavity 56 may be reciprocatably oscillated independently by diaphragms.

[105] Referring now to Figs. 10A-10C and 11A-11C, yet another specific embodiment of an aspiration modulation device 30d will be described. The aspiration modulation device 30d generally comprises a master unit 92, a slave unit 94, and flexible fluidic tubing 96 fluidly coupling the slave unit 94 to the master unit 92.

[106] The master unit 92 is similar to the aspiration modulation device 30a illustrated in Figs. 7A-7C, with the exception that the master unit 92 does not contain a pressure manifold. Instead, the master unit 92 comprises a cavity 56’ having a primary pressure chamber 56a’ and an output modulation port 98’ in fluid communication with the primary pressure chamber 56a’ and to which one end of the flexible fluidic tubing 96 is affixed. The slave unit 94 comprises a pressure manifold 46 having a secondary pressure chamber 56a” and an input modulation port 98” in fluid communication with the secondary pressure chamber 56a” and to which the other end of the flexible fluidic tubing 96 is affixed. The pressure manifold 46 also has the vacuum inlet 58, vacuum outlet 60 along with the vacuum flow control element 54, and vent inlet 62 (with fluidic tubing) along with the fluid refill control element 52. As will be described in further detail below, the entire master unit 92 may be reusable, while the entire slave unit 94 may be disposable.

[107] Like the aspiration modulation device 30a, the master unit 92 comprises a casing or housing 72’ containing the controller/processor 44, and on which the Ul 42 is affixed, while the slave unit 94 comprises a casing or housing 72” forming the pressure manifold 46 having the secondary pressure chamber 56a”, along with the vacuum inlet 58, vacuum outlet 60, vent inlet 62, fluid refill control element 52, and vacuum flow control element 54. In the illustrated embodiment, the casing 72’ of the master unit 92 is a two-part casing that comprises a top casing portion 72a’ and a bottom casing portion 72b’ that are removably coupled to each other. The sensor (not shown) is affixed to the casing 72” of the slave unit 94 in fluid communication with the secondary pressure chamber 56a”.

[108] In the embodiment illustrated in Figs. 10A-10C and 11A-11C, the aspiration modulation device 30d comprises a fluid pressure oscillator 50c that takes the form of a two-part drive diaphragm assembly. In particular, the fluid pressure oscillator 50c comprises a primary pressure transduction element 66d that takes the form of a diaphragm affixed within the cavity 56’ of the master unit 92, and a secondary pressure transduction element 66e that also takes the form of a diaphragm affixed within the manifold cavity 56” (shown best in Figs. 11A-11C) of the slave unit 94. The diaphragm 66d divides the cavity 56’ of the master unit 92 between the primary pressure chamber 56a’ containing a variable volume of primary pressure modulating fluid 74’ in fluid communication with the output modulation port 98’, and a primary working chamber 56b’ fluidly isolated from the output modulation port 98’. The primary pressure chamber 56a’ of the cavity 56’ is bounded by a bottom wall 76 and sidewall 78 of the casing 72’ and opposing diaphragm 66d.

[109] The diaphragm 66e divides the manifold cavity 56” of the slave unit 94 between a secondary pressure chamber 56a” containing a variable volume of secondary pressure modulating fluid 74” in fluid communication with the vacuum outlet 60, vacuum inlet 58, and vent inlet 62, and a secondary working chamber 56b” containing primary pressure modulating fluid 74’ fluidly isolated from the vacuum outlet 60, vacuum inlet 58, and vent inlet 62. Thus, it can be appreciated that the diaphragm 66e sterilely seals the primary pressure modulating fluid 74’ contained in the primary pressure chamber 56a’ of master unit 92, the fluidic tubing 96, and the secondary working chamber 56b” of the slave unit 94, from the secondary pressure modulating fluid 74” contained in the secondary pressure chamber 56a” of the slave unit 94, thereby preventing cross-contamination between the secondary pressure chamber 56a” and the primary pressure chamber 56a’, fluidic tubing 96, and secondary working chamber 56b”. A sterile covering (not shown) may be used to encase the master unit 92, so that the entire aspiration modulation device 30d may be used in the sterile field.

[110] The fluid pressure oscillator 50c further comprises the linear actuator 68a comprising the actuator housing 80 (e.g., a voice coil) and the rod 82 directly mechanically coupled to the diaphragm 66d via the coupling 84. The actuator housing 80 is contained within the top casing portion 72a’, while the rod 82 is disposed in the bottom casing portion 72b’. The diaphragm 66d of the master unit 92 is fluidly coupled to the diaphragm 66e of the slave unit 94 via the primary pressure modulating fluid 74’ contained in the primary pressure chamber 56a’ of the master unit 92, and the primary pressure modulating fluid 74’ contained in the fluidic tubing 96 and secondary working chamber 56b” of the slave unit 94.

[111] Thus, by reciprocatably moving the rod 82 from its nominal position away and towards the actuator housing 80, the diaphragm 66d may be reciprocatably flexed from its nominal flex state towards and away from the bottom wall 76 of the casing 72’ of the master unit 92 to reciprocatably oscillate the volume of primary pressure modulating fluid 74’, and thus the fluid pressure within, the primary pressure chamber 56a’ of the master unit 92. In turn, the volume of primary pressure modulating fluid 74’, and thus the fluid pressure within, the working chamber 56b” of the slave unit 92 may be reciprocatably oscillated, thereby reciprocatably flexing the diaphragm 66e from its nominal flex state towards and away from the bottom wall 76 of the casing 72” of the slave unit 94 to reciprocatably oscillate the volume of secondary pressure modulating fluid 74”, and thus the fluid pressure within the secondary pressure chamber 56a” of the slave unit 94.

[112] As illustrated in Fig. 10A, the rod 82 is in a nominal position relative to the actuator housing 80, such that the diaphragm 66d is in a nominal flex state relative to the bottom wall 76 of the casing 72’, and the primary pressure chamber 56a’ of the master unit 92, and thus the working chamber 56b” of the slave unit 94, has a nominal volume of primary pressure modulating fluid 74’ at a nominal pressure. Thus, as illustrated in Fig. 11 A, the diaphragm 66e is in a nominal flex state relative to the bottom wall 76 of the casing 72”, and the secondary pressure chamber 56a” of the slave unit 92 has a nominal volume of secondary pressure modulating fluid 74” at a nominal pressure (in this case, at the baseline vacuum pressure).

[113] As illustrated in Fig. 10B, when the rod 82 is linearly translated from its nominal position away from the actuator housing 80 (downward as shown by the arrow), the diaphragm 66d is flexed from its nominal flex state towards the bottom wall 76 of the casing 72’ of the master unit 92, thereby decreasing the volume of primary pressure modulating fluid 74’, and thus correspondingly increasing the fluid pressure from the baseline vacuum pressure, in the primary pressure chamber 56a’ of the master unit 92, fluidic tubing 96, and working chamber 56b” of the slave unit 94. In turn, as illustrated in Fig. 11B, the increased pressure of the primary pressure modulating fluid 74’ within the working chamber 56b” of the slave unit 94 flexes the diaphragm 66e from its nominal flex state towards the bottom wall 76 of the casing 72” of the slave unit 94, thereby decreasing the variable volume of secondary pressure modulating fluid 74” in the secondary pressure chamber 56a”, and thus correspondingly increasing the fluid pressure from the baseline vacuum pressure in the secondary pressure chamber 56a”.

[114] In contrast, as illustrated in Fig. 10C, when the rod 82 is linearly translated from its nominal position toward the actuator housing 80 (upward as shown by the arrow), the diaphragm 66d is flexed from its nominal flex state away from the bottom wall 76 of the casing 72’ of the master unit 92, thereby increasing the volume of primary pressure modulating fluid 74’, and thus correspondingly decreasing the fluid pressure from the baseline vacuum pressure, in the primary pressure chamber 56a’ of the master unit 92, fluidic tubing 96, and working chamber 56b” of the slave unit 94. In turn, as illustrated in Fig. 11C, the decreased pressure of the primary pressure modulating fluid 74’ within the working chamber 56b” of the slave unit 94 flexes the diaphragm 66e from its nominal flex state away from bottom wall 76 of the casing 72” of the slave unit 94, thereby increasing the variable volume of secondary pressure modulating fluid 74” in the secondary pressure chamber 56a”, and thus correspondingly decreasing the fluid pressure from the baseline vacuum pressure in the secondary pressure chamber 56a”.

[115] Advantageously, the slave unit 94 is removably coupled to the master unit 92 via the fluidic tubing 96, such that the master unit 92 can be made to be reusable, while the slave unit 94 can be made to be disposable. That is, after use, the entire slave unit 94, along with the fluidic tubing 96, can be disconnected from the master unit 92 and discarded, and replaced with a new slave unit 92 and fluidic tubing 96 for subsequent use. Alternatively, the slave unit 94 can be disconnected from the master unit 92, re-sterilized, and reconnected to the master unit 92 via new fluidic tubing 96. In this manner, the master unit 94, along with the more sensitive electronic components (which have been sterilely isolated from the secondary pressure modulating fluid 74” contained in the sterile secondary pressure chamber 56a” of the slave unit 94 via the diaphragm 66e need not be sterilized, thereby preventing thermal damage to the electronic components and/or obviating the need to design more expensive electronic componentry that can withstand one or more thermal cycles used during a typical sterilization procedure.

[116] Although the fluid pressure oscillator 50a is illustrated and described as comprising a pressure transduction element 66d in the form of a diaphragm and an actuator 68a that are respectively identical to the pressure transduction element 66a and actuator 68a illustrated in Figs. 7A-7C, it should be appreciated that the fluid pressure oscillator of alternative embodiments of an aspiration modulation device may be different from that illustrated in Figs. 10A-10C. For example, instead of having a direct drive diaphragm assembly, the fluid pressure oscillators may have an indirect drive diaphragm assembly, such as that illustrated in Figs. 8A-8C, or any other diaphragm-based assembly sufficient to oscillate the secondary pressure modulating fluid 74” contained in the sterile secondary pressure chamber 56a” of the slave unit 94 via the diaphragm 66e. For example, the diaphragm-based assembly may be a pneumatically or hydraulically driven diaphragm assembly; that is, the valve system of a pneumatic actuator may be incorporated into master unit. In this case, the entire cavity 56’ of the master unit 92 will operate as a working chamber that communicates air from the high pressure and low pressure valves to the working chamber 56b” of the slave unit 94 via the fluidic tubing 96, thereby alternately flexing the diaphragm 66e towards and away from the bottom wall 76 of the casing 72” of the slave unit 94 to alternately decrease and increase the variable volume of pressure modulating fluid 74” in the pressure chamber 56a”, thus correspondingly increasing and decreasing the fluid pressure from the baseline vacuum pressure in the pressure chamber 56a”.

[117] Referring now to Figs. 12-13, yet another specific embodiment of an aspiration modulation device 30e will be described. The aspiration modulation device 30e is similar to the aspiration modulation device 30d illustrated in Figs. 10A-10C and 11A-11C in that the aspiration modulation device 30e generally comprises a master unit 92’ and a slave unit 94’. However, instead of distributing fluidic components between the master unit 92’ and the slave unit 94’ and fluidly connecting the master unit 92’ and slave unit 94’ via fluidic tubing, the master unit 92’ comprises a housing or casing 72’ carrying only electronic components of the aspiration modulation device, e.g., the Ul 42, controller/processor 44 (not shown in Figs. 12-13), and driver 70 (not shown in Figs. 12-13), while the slave unit 94’ comprises a housing or casing 72” carrying all of the fluidic and mechanical components of the aspiration modulation device, e.g., the pressure transduction element 66 and actuator 68, as well as the pressure manifold 46, including the vacuum inlet 58, vacuum outlet 60 (along with the vacuum flow control element 54 (not shown in Figs. 12-13)), and vent inlet 62 (along with the fluid refill control element 52 (not shown in Figs. 12-13)). The fluid pressure oscillator 50 may, e.g., take the form of either of the fluid pressure oscillators 50a, 50b described herein. In the illustrated embodiment, the master unit 92’ take the form of an insert that can be disposed within the slave unit 94’, such that an electrical connection is made between the master unit 92’ and the slave unit 94’. For example, the slave unit 94’ may have a housing or casing 72 having a space in which the master unit 92’ may be inserted. The slave unit 94’ may further have a lid 99 that can be closed once the master unit 92’ has been inserted into the slave unit 94’ to provide an integrated and compact unit. In an alternative embodiment, the master unit 92’ is not physically connected to the slave unit 94’ to provide an electrical connection therebetween, but rather remains remote from, and wirelessly communicates with, the slave unit 94’.

[118] In the same manner that the slave unit 94 is removably coupled to the master unit 92 in the aspiration modulation device 30d illustrated in Figs. 10A-10C and 11A-11C, such that the master unit 92 can be made to be reusable, while the slave unit 94 can be made to be disposable, the master unit 92’ may be removed from the slave unit 94’ of the aspiration modulation device 30e illustrated in Figs. 12-13, such that the slave unit 94’ without the master unit 92’ can be discarded. The master unit 92’ may then be inserted into a new slave unit 94’ for subsequent use.

[119] Referring now to Figs. 14A-14C, an embodiment of an aspiration pulsing device 30f will be described. The aspiration pulsing device 30f is similar to the aspiration modulation devices 30a-30e described above in that the aspiration pulsing device 30f comprises a pressure manifold 46 comprising a manifold cavity 56 having a pressure chamber 56a and a working chamber 56b, a vacuum inlet 58 configured forfluidly coupling the aspiration catheter 22 (shown in Fig. 3) to the pressure chamber 56a, and a vacuum outlet 60 configured for fluidly coupling the vacuum source 24 (shown in Fig. 3) to the pressure chamber 56a. Similar to the aspiration modulation devices 30a-30e described above, the aspiration modulation device 30f also comprises a diaphragm 66f affixed within the manifold cavity 56 forfluidly isolating the pressure chamber 56a from the working chamber 56b, and configured for transmitting clog clearing pressure to aspiration fluid 74 contained in the pressure chamber 56a.

[120] The aspiration pulse device 30f provides the same advantage as the previously described aspiration modulation devices 30a-30e in that the diaphragm 66f sterilely seals the working chamber 56b from the aspiration fluid 74 contained in the pressure chamber 56a of the manifold cavity 56, thereby preventing crosscontamination between the pressure chamber 56a and the working chamber 56b. Furthermore, the aspiration pulsing device 30f may transmit clog clearing pressure through the aspiration lumen 34 of the aspiration catheter 22 without using any saline. Thus, not only is a connection to a source of saline not required, no saline will be mixed with tissue removed from the patient, thereby allowing the capacity of the aspirate collection container 28 to be entirely reserved for such removed tissue, as well as allowing the nature and the amount of such removed tissue to be determined via a quick inspection of the aspiration collection container 28. Furthermore, like the previously described aspiration modulation devices 30a-30e, because the working chamber 56b of the manifold cavity 56 is isolated from the aspiration fluid 74 contained in the pressure chamber 56a, the aspiration pulse device 30f does not require a check valve between the vacuum source 24 and the pressure chamber 56a.

[121] However, unlike the previously described aspiration modulation devices 30a-30e, instead of modulating a vacuum pressure applied to the pressure chamber 56a by the vacuum source 24, the diaphragm 66f, in response to different pressures within the working chamber 56b, fluidly decouples the vacuum source 24 from the pressure chamber 56a and then applies the clog clearing pressure in the form of a pressure pulse or sequence of pulses to the aspiration fluid 74 contained in the pressure chamber 56a to facilitate subsequent ingestion of a thrombus clogging the aspiration catheter 22, and then once the pressure pulse(s) has completed, the diaphragm 66f fluidly recouples the vacuum source 24 to the pressure chamber 56a to ingest the thrombus within the aspiration catheter 22. [122] To this end, pressure manifold 46 further comprises an additional pressure port 64 configured for fluidly coupling a pressure control device (not shown in Figs. 14A-14C) to the working chamber 56b. The pressure control device may apply pressure at various levels to working fluid 74’ contained in the working chamber 56b to switch the diaphragm 66f from an aspiration state (see Fig. 14A) to a pulsing state (see Figs. 14B-14C). When in its aspiration state, the diaphragm 66f fluidly couples the vacuum source 24 to the pressure chamber 56a for providing vacuum pressure to the pressure chamber 56a to effect normal aspiration via the aspiration catheter 22. In contrast, when in its pulsing state, the diaphragm 66f decouples the vacuum source 24 from the pressure chamber 56a to pause normal aspiration via the aspiration catheter 22, thereby pressure coupling the working chamber 56b to the pressure chamber 56a in a dedicated manner (i.e. , without influence by the vacuum source 24), and applies pressure to the aspiration fluid 74 contained in the pressure chamber 56a in an effort to agitate a thrombus clogging the aspiration catheter 22. Once the thrombus is cleared from the aspiration catheter 22, the pressure control device may continually apply pressure at an appropriately low level to the working fluid 74’ contained in the working chamber 56b to switch the diaphragm 66f from its pulsing state (see Figs. 14B-14C) back to, and maintain in, its aspiration state (see Fig. 14A) to fluidly recouple the vacuum source 24 to the pressure chamber 56a to provide a vacuum pressure to the pressure chamber 56a and return back to normal aspiration (reset the vacuum pressure) via the aspiration catheter 22.

[123] In particular, the diaphragm 66f comprises a circular center sealing region 67 (best shown in Figs. 15A and 15B) that is aligned with the vacuum outlet 60. The vacuum outlet 60 protrudes into the pressure chamber 56a toward the diaphragm 66f (in this case, from the bottom of the pressure manifold 46 upwards into the pressure chamber 56a) to facilitate interaction between the circular center sealing region 67 of the diaphragm 66f and the vacuum outlet 60, and in particular, to seal the vacuum outlet 60 when the diaphragm 66f is in its sealing state, and to unseal the vacuum outlet 60 when the diaphragm 66f is in its aspiration state, as will be described in further detail below. The diaphragm 66f may optionally comprise an annular protrusion (or O-ring) 69 that makes contact with and seals the vacuum outlet 67. As will also be described in further detail below, the diaphragm 66f further comprises annular pulsing region 71 (best shown in Figs. 15A and 15B) located between the vacuum outlet 60 and the inner surface of the manifold cavity 56 to facilitate unimpinged deflection of the annular pulsing region 71 of the diaphragm 66f when the diaphragm 66f is in its sealed pulsing state. Preferably, the diaphragm 66f has a biasing force (e.g., using one or more springs (not shown) or by having a passive restorative force) that urges the diaphragm 66f from its pulsing state to its aspiration state.

[124] When the pressure control device applies a relatively low pressure to the working fluid 74’ contained in the working chamber 56b that remains below a sealing pressure threshold (e.g., such that the fluid pressure differential between the working chamber 56b and the pressure chamber 56a is negative, zero, or even has slightly positive value that does not overcome the biasing force applied or intrinsic to the diaphragm 66f), the diaphragm 66f will remain in its aspiration state (as illustrated in Fig. 14A) to continue fluidly coupling the vacuum source 24 to the pressure chamber 56a, such that normal aspiration via the aspiration catheter 22 proceeds.

[125] When the pressure control device applies a relatively moderate pressure or higher pressure to the working fluid 74’ contained in the working chamber 56b that exceeds the sealing pressure threshold (e.g., such that the fluid pressure differential between the working chamber 56b and the pressure chamber 56a overcomes the biasing force applied or intrinsic to the diaphragm 66f), the diaphragm 66f will deflect (in this case, downward) toward the vacuum outlet 60 from its aspiration state (Fig. 14A) to its pulsing state (Fig. 14B), such that the circular center sealing region 67 contacts and seals vacuum outlet 60, thereby decoupling the vacuum source 24 from the pressure chamber 56a.

[126] When the pressure control device applies a relatively high pressure to the working fluid 74’ contained in the working chamber 56b (e.g., having a magnitude significantly higher than the relatively moderate pressure, but less than the blood pressure of the patient, such as atmospheric pressure), the annular pulsing region 71 of the diaphragm 66f will deflect (in this case, downward) into the pressure chamber to its sealed pulsing state (Fig. 14C), thereby applying pressure, and in the preferred embodiment, a pressure pulse output, to the aspiration fluid 74 contained within the pressure chamber 56.

[127] When the pressure control device again applies a relatively low pressure to the working fluid 74’ contained in the working chamber 56b that is below an unsealing pressure threshold (e.g., such that the sum of the net force applied to the center sealing region 67 of the diaphragm 66f by the pressure differential between the working chamber 56b and the sealed vacuum outlet 60, the net force applied to the annular pulsing region 71 of the diaphragm 66f by the pressure differential between the working chamber 56b and the pressure chamber 56a, and the biasing force applied or intrinsic to the diaphragm 66f is negative (i.e., towards the working chamber 56b)), the annular pulsing region 71 of the diaphragm 66f will deflect (in this case, upward) away from the pressure chamber 56a (Fig. 14B), and the diaphragm 66f will further deflect (in this case, upward), to then transition from its pulsing state (Fig. 14B) back to its aspiration state (Fig. 14A), such that the circular center sealing region 67 no longer contacts and unseals vacuum outlet 60, thereby recoupling the vacuum source 24 to the pressure chamber 56a.

[128] It should be appreciated that each of the sealing pressure threshold and unsealing pressure threshold may vary in accordance with whether the aspiration catheter 22 is clogged with a thrombus or clear of a thrombus.

[129] In particular, prior to the diaphragm 66f transitioning from its aspiration state to its pulsing state, the vacuum pressure applied by the vacuum source 24 to the pressure chamber 56a will vary depending on the aspiration flow conditions. For example, the vacuum pressure applied to the pressure chamber 56a will be significantly lower during a no flow condition (i.e., the aspiration catheter 22 is clogged with a thrombus) than the vacuum pressure applied to the pressure chamber 56a during a mixed flow condition (i.e., the aspiration catheter 22 is actively ingesting a thrombus), which will be significantly lower than the vacuum pressure applied to the pressure chamber 56a during a free flow condition (i.e., the aspiration catheter 22 is only ingesting bodily fluid), Accordingly, the sealing pressure threshold will be significantly lower during a no flow condition than the sealing pressure threshold during a mixed flow condition, which will be significantly lower than the sealing pressure threshold during a free flow condition. However, during normal operation, the pressure control device will only be operated (either manually, semi-automatically, or automatically) in response to a no flow condition, as will be described in further detail below. In this case, the sealing pressure threshold will generally be relatively low, e.g., at or near the vacuum pressure applied to the pressure chamber 56a by the vacuum source 24 when the aspiration catheter 22 is clogged with a thrombus, subject to the biasing force applied or intrinsic to the diaphragm 66f.

[130] Prior to the diaphragm 66f transitioning from its pulsing state back to its aspiration state (i.e., the vacuum source 24 remains fluidly decoupled from the pressure chamber 56a), the pressure in the pressure chamber 56a will vary depending on whether the aspiration catheter 22 is clogged with a thrombus or cleared of a thrombus, as discussed above. In particular, when the aspiration catheter 22 is clogged with a thrombus, the working chamber 56b will be robustly pressure coupled to the pressure chamber 56b , such that the pressure in the pressure chamber 56b will vary in accordance with the pressure in the working chamber 56a. However, the pressure at the sealed vacuum outlet 60 will be at a very low vacuum pressure. In contrast, when the aspiration catheter 22 is cleared of a thrombus, the pressure in the pressure chamber 56b will be relatively high (e.g., at or near blood pressure). Accordingly, the unsealing pressure threshold will be significantly lower when the aspiration catheter 22 is clogged with a thrombus than the unsealing pressure threshold when the aspiration catheter 22 is cleared of a thrombus. Indeed, the unsealing pressure threshold will be lower than the sealing pressure threshold primarily due to relatively low vacuum level of the sealed vacuum outlet 60 exerted on the circular sealing region 67 of the diaphragm 66f. However, when normal aspiration is needed after clearing the clogged thrombus from the aspiration catheter 22, the unsealing pressure threshold will be at its highest, thereby more easily triggering the diaphragm 66f to transition from its pulsing state back to its aspiration state, and in fact, may facilitate the diaphragm 66f to transition from its pulsing state back to its aspiration state even if the pressure in the working chamber 56b is at atmosphere. In contrast, when the aspiration catheter 22 is still clogged with the thrombus, the unsealing pressure threshold will be at its lowest, thereby making it more difficult to trigger the diaphragm 66f to transition from its pulsing state back to its aspiration state. However, pulsing of the aspiration fluid 74’ within the pressure chamber 56a is still needed at this point in time.

[131] Referring now to Fig. 16A, the progression of the pressures within the pressure chamber 56a and at the vacuum outlet 60 in response to the application of an exemplary pressure waveform 73a to the working chamber 56b during free-flow (i.e. , the aspiration catheter 22 is clear of a thrombus) and no-flow conditions (i.e. , the aspiration catheter 22 is clogged with a thrombus).

[132] During the free-flow condition, the unsealed vacuum outlet 60, and correspondingly the pressure chamber 56a, is at a relatively moderate free-flow vacuum pressure level. During the free-flow condition, the exemplary pressure waveform input 73a, by default, is at a relatively low vacuum pressure level 75a at or near a no-flow vacuum pressure. Notably, the low vacuum pressure level 75a of the pressure waveform input 73a applied to the working chamber 53b is far below an exemplary sealing pressure threshold 77a, and thus, the diaphragm 66f will remain in the aspiration state to effect normal aspiration.

[133] During the no-flow condition, the unsealed vacuum outlet 60, and correspondingly the pressure chamber 56a, drop to a relatively low no-flow vacuum pressure level. Preferably, concurrently or at some period of time after the pressure chamber 56a drops to the low no-flow vacuum pressure, the pressure waveform input 73a will have a pressure pulse input 75b that rises to a relatively high pressure level (e.g., atmospheric pressure). For the purposes of illustration, the pressure pulse input 75b is trapezoidal in nature, although it should be appreciated that the pressure pulse input 75b can have any suitable shape. As the pressure pulse input 75b rises, the unsealed vacuum outlet 60, and correspondingly the pressure chamber 56a, remain at the low no-flow vacuum pressure level until the pressure pulse input 75b reaches the sealing pressure threshold 77a.

[134] Once the pressure pulse input 75b reaches or exceeds the sealing pressure threshold 77a, the diaphragm 66f will transition from its aspiration state to its pulsing state; that is, the vacuum source 24 will be fluidly decoupled from the pressure chamber 56a by sealing the vacuum outlet 60. As a result, the pressure chamber 56a will be robustly pressure coupled to the working chamber 56b. Although the sealed vacuum outlet 60 will remain at the low no-flow vacuum pressure, the pressure level of the pressure chamber 56a will rapidly rise to and then track the pressure level of the working chamber 56b (with an offset equal to any biasing force applied or intrinsic to the diaphragm 66f and the elasticity of the diaphragm 66f). Thus, in response to the application of the pressure pulse input 75b to the working chamber 56b, a pressure pulse output 75b’ will be transmitted or applied to the pressure chamber 56a via the diaphragm 66f. As the pressure pulse input 75b drops, the pressure level of the pressure chamber 56a continues to track the pressure level of the working chamber 56b until the pressure pulse input 75b reaches the unsealing pressure threshold 77b. It should be appreciated that the unsealing pressure threshold 77b is lower than the sealing pressure threshold 77a illustrated in Fig. 16A due primarily to the force needed to overcome the low vacuum pressure exerted on the circular sealing region 67 of the diaphragm 66f.

[135] Assuming that the thrombus has not been cleared from the aspiration catheter 22, the pressure pulse input 75b will reach or drop below the unsealing pressure threshold 77b, thereby transitioning the diaphragm 66f from its pulsing state back to its aspiration state; that is, the vacuum source 24 will be fluidly recoupled to the pressure chamber 56a by unsealing the vacuum outlet 60. As a result, the pressure level of the pressure chamber 56a will stop tracking the pressure level of the working chamber 56b and drop rapidly back to the low no-flow vacuum pressure level in correspondence with the low no-flow vacuum pressure level of the vacuum outlet 60. The exemplary pressure waveform input 73a then drops to its default low vacuum pressure level 75c, after which another pressure waveform input 73a may have another pressure pulse input 75b.

[136] In contrast, assuming that the thrombus has been cleared from the aspiration catheter 22 at some point during the pressure pulse input 75b, the pressure level of the pressure chamber 56a will stop tracking the pressure level of the working chamber 56b and immediately increase to or near blood pressure, thereby causing the unsealing pressure threshold 77b to increase above the peak of the pressure pulse input 75b, as illustrated in Fig. 16B. Since the pressure pulse input 75b will be below the unsealing pressure threshold 77b, the diaphragm 66f will transition from its pulsing state back to its aspiration state; that is, the vacuum source 24 will be fluidly recoupled to the pressure chamber 56a by unsealing the vacuum outlet 60. As a result, the pressure level of the pressure chamber 56a will drop rapidly from blood pressure or near blood pressure ideally back to the moderate free-flow vacuum pressure level in correspondence with the moderate free-flow vacuum pressure level of the vacuum outlet 60. Notably, in some cases, the pressure level in the pressure chamber 56a may not robustly drop down to the moderate free-flow vacuum pressure level, in which case, the diaphragm 66f may undergo oscillation between the aspiration state and the pulsing state, or the diaphragm 66f will not fully deflect upward, such that the vacuum outlet 60 is fluidly coupled in an attenuated manner to the pressure chamber 56a. However, the exemplary pressure waveform input 73a will preferably subsequentially drop to its default low vacuum pressure level 75b, thereby ensuring that the diaphragm 66f completely and continuously remains in its aspiration state until actively triggered to transition to its pulsing state.

[137] Although the pressure waveform input 73a illustrated in Figs. 16A-16B is described as having a single (only one) pressure pulse input 75b during each pulsed state of the diaphragm 66f, in an alternative embodiment illustrated in Fig. 17, a pressure waveform input 73a’ may have a series of pressure pulse inputs 75b (in this case, three pressure pulse inputs 75b1-75b3) during each pulse state of the diaphragm 66f. In particular, once the first pressure pulse input 75b1 reaches or exceeds the sealing pressure threshold 77a, the diaphragm 66f will transition from its aspiration state to its pulsing state to seal the vacuum outlet 60 and fluidly decouple the vacuum source 24 from the pressure chamber 56a. In the same manner described above with respect to Fig. 16A, the sealed vacuum outlet 60 will remain at the low noflow vacuum pressure, while the pressure level of the pressure chamber 56a will rapidly rise to and then track the pressure level of the working chamber 56b. Thus, in response to the application of the first pressure pulse input 75b1 to the working chamber 56b, a first pressure pulse output 75bT will be transmitted or applied to the pressure chamber 56a via the diaphragm 66f. As the first pressure pulse input 75b1 drops, the pressure level of the pressure chamber 56a continues to track the pressure level of the working chamber 56b in the same manner described above with respect to Fig. 16A. However, the first pressure pulse input 75b1 never reaches the unsealing pressure threshold 77b. That is, unlike the base of the single pressure pulse input 75b illustrated in Fig. 16A, which is below the unsealing pressure threshold 77b, the base of the trailing edge of the first pressure pulse input 75b1 is above the unsealing pressure threshold 77b. Thus, the diaphragm 66f will not transition from its pulsing state back to its aspiration state. Instead, the pressure waveform input 73a’ has a second pressure pulse input 75b2 and a third pressure pulse input 75b3 that is applied to the working chamber 56b, thereby transmitting or applying a second pressure pulse output 75b2’ and then a third pressure pulse output 75b3’ to the pressure chamber 56a via the diaphragm 66f. Notably, the bases of both the rising edge and the trailing edge of the second pressure pulse input 75b2, and the base of the rising edge of the third pressure pulse input 75b3 are above the unsealing pressure threshold 77b, and thus, the diaphragm 66f will not transition from its pulsing state back to its aspiration state.

[138] Assuming that the thrombus has not been cleared from the aspiration catheter 22, the third pressure pulse input 75b3 will reach or drop below the unsealing pressure threshold 77b, thereby transitioning the diaphragm 66f from its pulsing state back to its aspiration state; that is, the vacuum source 24 will be fluidly recoupled to the pressure chamber 56a by unsealing the vacuum outlet 60. Thus, in the same manner discussed above with respect to Fig. 16A, the pressure level of the pressure chamber 56a will stop tracking the pressure level of the working chamber 56b and drop rapidly back to the low no-flow vacuum pressure level in correspondence with the low no-flow vacuum pressure level of the vacuum outlet 60. The exemplary pressure waveform input 73a then drops to its default low vacuum pressure level 75b, after which the pressure waveform input 73a’ may have another series of pressure pulse inputs 75b1 -75b3.

[139] In contrast, assuming that the thrombus has been cleared from the aspiration catheter 22 at some point during the series of pressure pulse inputs 75b1- 75b3, the pressure level of the pressure chamber 56a will stop tracking the pressure level of the working chamber 56b and immediately increase to or near blood pressure, thereby causing the unsealing pressure threshold 77b to increase above the peak of the pressure pulse input 75b, and triggering the diaphragm 66f to transition from its pulsing state back to its aspiration state in the same manner described above with respect to Fig. 16B.

[140] The pressure control device can be any device capable of applying a waveform to the working fluid 74’ contained in the working chamber 56b in a manner that transitions the diaphragm 66f between the aspiration state and the sealed pulsing state. In the preferred embodiment, the pressure control device is pneumatic in nature, in which case, the working fluid 74’ is a gas (e.g., air), such that the response time of the diaphragm 66f is quicker when the pressure control device applies the pressure at various levels to the working fluid 74’. It should be noted that, because the diaphragm 66f fluidly isolates the pressure chamber 56a from the working chamber 56b, any risk of the gas entering into the blood stream of the patient is eliminated. In an alternative embodiment, the pressure control device is hydraulic in nature, in which case, the working fluid 74’ is a liquid (e.g., saline). Although the response time of the diaphragm 66f may be relatively slow when the working fluid 74’ is liquid (due to its higher viscosity), due to its incompressibility, the initial pulse spike may be higher compared to a more oscillatory lower initial pulse spike in the pulse resulting when using a gas with more compressibility.

[141] In one embodiment illustrated in Fig. 17A, a pressure control device 25’ comprises a controller 45 and a three-way valve 47 having two input ports 49a, 49b respectively connected to a source of high pressure (e.g., atmosphere) and a source of low pressure (e.g., vacuum supplied by a vacuum source preferably different from the vacuum source 24), and one output port 49c connected to the pressure port 64 of the pressure manifold 46. The controller 45 is configured for operating the three-way valve 47 (e.g., via a solenoid (not shown)) to either fluidly couple the input port 49a connected to the vacuum source 24 to the output port 49c, such that the relatively low pressure level is applied to the working fluid 74’ contained in the working chamber 56b, thereby transitioning the diaphragm 66f to its aspiration state (Fig. 14A), or fluidly couple the input port 49b connected to atmosphere to the output port 49c, such that the relatively high pressure level is applied to the working fluid 74’ contained in the working chamber 56b, thereby transitioning the diaphragm to the its pulsing state (Figs. 14B-14C)

[142] The controller 45 may be configured for operating the three-way valve 47, such that a series of alternating high pressure (atmospheric) pulse inputs 81 a and low pressure (vacuum) pulse inputs 81 b, as illustrated in Fig. 18A, is applied to the working fluid 74’ contained in the working chamber 56b. As shown in Fig. 18A, the magnitude of the peak of each of the high pressure pulse inputs 81 a is above the sealing pressure threshold, thereby transitioning the diaphragm 66f from its aspiration state to its pulsing state . In contrast, the magnitude of the valley of each of the low pressure pulse inputs 81 b is below the unsealing pressure threshold, thereby transitioning the diaphragm 66f from its pulsing state to its aspiration state. Thus, in response to the application of the pressure waveform input to the working fluid 74’ contained in the working chamber 56b, the diaphragm 66f will repeatedly cycle from its aspiration state to its pulsing state, and then from its pulsing state back to its aspiration state.

[143] Alternatively, the controller 45 may be configured for operating the three- way valve 47, such that a series of high pressure (atmospheric) pulse inputs 81a on a baseline low pressure input 81c, as illustrated in Fig. 18B, is applied to the working fluid 74’ contained in the working chamber 56b. As shown in Fig. 18B, the magnitude of the peak each of the high pressure pulse inputs 81 a is above the sealing pressure threshold, thereby transitioning the diaphragm 66f from its aspiration state (Fig. 14A) to its pulsing state (Figs. 14B-14C). In contrast, the magnitude of the base of each of the low pressure pulse inputs 81 b is below the unsealing pressure threshold, thereby transitioning the diaphragm 66f from its pulsing state to its aspiration state. Thus, in response to the application of the pressure waveform input to the working fluid 74’ contained in the working chamber 56b, the diaphragm 66f will repeatedly cycle from its aspiration state to its pulsing state, and from its pulsing state back to its aspiration state. [144] In a preferred embodiment, the pressure control device 25’ may further comprise the previously described sensor 48. In this case, the controller 45 may optionally operate the three-way valve 47 in response to a signal from the sensor 48 indicating that that a clogging event has occurred (i.e. , the aspiration catheter 22 is clogged with a thrombus) ora clearing event has occurred (i.e., the thrombus has been ingested by the aspiration catheter 22). For example, if the signal output by the sensor 48 indicates that a clogging event has occurred, the controller 45 may operate the three-way valve 47 to apply the series of alternating high pressure pulse inputs 81 a and low pressure pulse inputs 81 b illustrated in Fig. 18A or the series of high pressure pulse inputs 81 a on the baseline low pressure input 81 c illustrated in Fig. 18B, to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f cycles between its aspiration and its pulsing state in an attempt to agitate and clear the thrombus from the aspiration catheter 22. In contrast, if the signal output by the sensor 48 indicates that a clearing event has occurred, the controller 45 may operate the three-way valve 47 to continuously apply the baseline low pressure input 81 c to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f is maintained in its aspiration state to effect normal aspiration. In this manner, the pressure control device 25’ may be fully-automated.

[145] In an alternative embodiment, the pressure control device 25’ may be semiautomated in that, instead of using a sensor 48, the controller 45 receives an input from a user (e.g., toggling a switch or pushing a button). For example, in response to an input by a user informed of a clogging event, may operate the three-way valve 47 to apply the series of alternating high pressure pulse inputs 81 a and low pressure pulse inputs 81 b illustrated in Fig. 18A or the series of high pressure pulse inputs 81 a on the baseline low pressure input 81 c illustrated in Fig. 18B, to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f cycles between its aspiration state and its pulsing state in an attempt to agitate and clear the thrombus from the aspiration catheter 22. In contrast, in response to an input by the user informed by a clearing event, the three-way valve 47 may continuously apply the low pressure (vacuum) to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f is maintained in its aspiration state to effect normal aspiration. Alternatively, the three-way valve 47 may be operated, after a predetermined number of high pressure pulse inputs have been applied to the working fluid 74’ contained in the working chamber 56b, to then apply the low pressure (vacuum) to the working fluid 74’ contained in the working chamber 56b.

[146] Referring to Fig. 17B, instead of a controller 45, a pressure control device 25” may comprise a user input device 51 (e.g., a toggle switch or a button) that manually operates the three-way valve 47 (e.g., via solenoid)(not shown). That is, for each input into the user input device 51 , a trigger signal is sent to the three-way valve 47, which applies a single high pressure input pulse to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f transitions from its aspiration state to its pulsing state in an attempt to agitate and clear the thrombus from the aspiration catheter 22. The three-way valve 47 will then apply a low pressure input to the working fluid 74’ contained in the working chamber 56b (e.g., by removing the high pressure pulse inputs 81 a from the working fluid 74’ contained in the working chamber 56b illustrated in Fig. 18A or by applying the low pressure pulse inputs 81 b illustrated in Fig. 18B), such that the diaphragm 66f transitions from its pulsing state back to its aspiration state to effect normal aspiration.

[147] In another embodiment illustrated in Fig. 16C, the pressure control device 25’ comprises a pressure generator 53 connected to the pressure port 64 of the pressure manifold 46. The pressure generator 53 is capable of applying an arbitrary pressure input to the working fluid 74’ contained in the working chamber 56b. For example, an exemplary pressure waveform input illustrated in Fig. 17C comprises a primary baseline low pressure (vacuum) 81c and a secondary baseline moderate pressure 81 d modulated with high pressure pulse inputs 81 a. As shown in Fig. 17C, the magnitude of the peak of each of the high pressure pulse inputs 81 a is above the sealing pressure threshold, thereby transitioning the diaphragm 66f from its aspiration state (Fig. 14A) to its pulsing state (Figs. 14B-14C). The magnitude of the base of each of the low pressure pulse inputs 81 b is above the unsealing pressure threshold, such that the diaphragm 66f does not transition from its pulsing state back to its aspiration state. Thus, in response to the application of the pressure waveform input to the working fluid 74’ contained in the working chamber 56b, the diaphragm 66f will transition from its aspiration state to its pulsing state, where there will be a series high pressure pulse inputs 81 a for a period of time, and will only transition from its pulsing state back to its aspiration state when the primary baseline low pressure (vacuum) 81c is below the unsealing pressure threshold. [148] Preferably, the pressure control device 25”’ further comprises the previously described sensor 48. In this case, the pressure generator 53 may be operated in response to a signal from the sensor 48 indicating that that a clogging event has occurred (i.e., the aspiration catheter 22 is clogged with a thrombus) or a clearing event has occurred (i.e., the thrombus has been ingested by the aspiration catheter 22). For example, if the signal output by the sensor 48 indicates that a clogging event has occurred, the pressure generator 53 may apply the baseline moderate pressure 81 d modulated with high pressure pulse inputs 81 a to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f transitions from its aspiration state to its pulsing statein an attempt to agitate and clear the thrombus from the aspiration catheter 22. In contrast, if the signal output by the sensor 48 indicates that a clearing event has occurred, the pressure generator 53 may apply the low pressure (vacuum) 81 c to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f transitions from its pulsing state to, and maintained in, its aspiration state to effect normal aspiration. In this manner, the pressure control device 25’” may be fully-automated.

[149] In an alternative embodiment, the pressure control device 25’” may be semiautomated in that, instead of using a sensor 48, the pressure generator 53 receives an input from a user (e.g., toggling a switch or pushing a button). For example, in response to an input from a user informed of a clogging event, the pressure generator 53 may be triggered to apply the baseline moderate pressure 81 d modulated with high pressure pulse inputs 81 a to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f transitions from its aspiration state to its pulsing state in an attempt to agitate and clear the thrombus from the aspiration catheter 22. In contrast, in response to an input form a user informed of a clearing event (or alternatively, after a predetermined number of pulse inputs 81 a have been applied to the working fluid 74’ contained in the working chamber 56b, the pressure generator 53 may be triggered to apply the low pressure (vacuum) to the working fluid 74’ contained in the working chamber 56b, such that the diaphragm 66f is maintained in its aspiration state to effect normal aspiration.

[150] It should be noted that the diaphragm 66f will apply pressure pulse outputs to the aspiration fluid 74 contained in the pressure chamber 56a in correspondence with the high pressure pulse inputs applied to the working fluid 74’ (e.g., any of the high pressure pulse inputs 81a illustrated in Figs. 18A-18C). In one embodiment, the shape of the high pressure pulse outputs corresponds to the shape of the high pressure pulse inputs. For example, the pressure pulse outputs may be rectangular in shape in correspondence with the rectangular shape of the high pressure pulse inputs (as illustrated in Figs. 18A-18C). In optional embodiments, the high pressure pulse inputs may have shapes other than rectangular, in which case, the pressure pulse outputs may be non-rectangular in shape in correspondence with the non-rectangular shape of the high pressure pulse inputs.

[151] In another optional embodiment, the diaphragm 66f may be configured for modulating the high pressure pulse inputs applied to the working fluid 74’ contained in the working chamber 56b, such that the high pressure pulse outputs applied to the aspiration fluid 74 contained in the pressure chamber 56a correspond to modulated pressure pulse inputs. For example, the physical properties (e.g., thickness, stiffness, shape, material, reinforcements, etc.) of the pulsing region 71 of the diaphragm 66f may be selected in a manner that modulates (or amplifies) the high pressure pulse inputs. In this manner, as illustrated in Fig. 19, if high pressure pulse inputs 81a applied to the working fluid 74’ contained in the working chamber 56b are rectangular in nature, the diaphragm 66f may modulate the high pressure pulse inputs 81 a, such that the pressure pulse outputs 81 a’ applied to the aspiration fluid 74 contained in the pressure chamber 56a may be non-rectangular. For example, the deflection of diaphragms may not occur uniformly across their surfaces or across the range of different pressure differentials. For example, as can be appreciated from Fig. 15B, different areas of the diaphragm 66b may deform non-uniformly. Likewise, for a given area of the diaphragm 66b, the magnitude of deformation may change non-linearly with respect to the pressure differential. Thus, a very uniform or regularized input pressure waveform (in this case, a series of pressure pulse inputs) may result in a highly complex output pressure waveform (in this case, a series of pressure pulse outputs).

[152] Although particular embodiments have been shown and described herein, it will be understood by those skilled in the art that they are not intended to limit the disclosed inventions, and it will be obvious to those skilled in the art that various changes, permutations, and modifications may be made (e.g., the dimensions of various parts, combinations of parts) without departing from the scope of the disclosed inventions, which is to be defined only by the following claims and their equivalents. The specification and drawings are, accordingly, to be regarded in an illustrative rather than restrictive sense. The various embodiments shown and described herein are intended to cover alternatives, modifications, and equivalents of the disclosed inventions, which may be included within the scope of the appended claims.

NUMBERED EMBODIMENTS OF THE INVENTION

1. An aspiration modulation device for use with an aspiration catheter and a vacuum source, comprising: a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber; a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter; a controller configured for, in response to the measured parameter, dynamically modifying a waveform signal corresponding to a modulated therapeutic pressure waveform; and a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, thereby modulating a vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

2. The aspiration modulation device of embodiment 1 , wherein the pressure manifold further has a vent inlet configured for fluidly coupling a pressurized fluid source to the pressure chamber, the aspiration modulation device further comprising a fluid refill control element configured for selectively fluidly coupling the pressurized fluid source to the pressure chamber.

3. The aspiration modulation device of embodiment 2, wherein, when a fluid pressure within the pressure chamber drops below a threshold fluid pressure, the fluid refill control element is configured for conveying pressure modulating fluid from the pressurized fluid source into the pressure chamber.

4. The aspiration modulation device of any of embodiments 1-3, wherein the sensor is a force feedback sensor configured for measuring a force output of the fluid pressure oscillator. 5. The aspiration modulation device of any of embodiments 1-3, wherein the sensor is a pressure sensor.

6. The aspiration modulation device of embodiment 5, wherein the pressure sensor is configured for measuring a fluid pressure within the pressure chamber.

7. The aspiration modulation device of any of embodiments 1-6, wherein the fluid pressure oscillator comprises: a pressure transduction element configured for interfacing with the pressure modulating fluid within the pressure chamber; an actuator configured for being operably coupled to the pressure transduction element; and a driver configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform.

8. The aspiration modulation device of embodiment 7, wherein the pressure transduction element comprises a movable manifold boundary, and wherein the driver is configured for controlling the actuator to reciprocatably move the movable manifold boundary.

9. The aspiration modulation device of embodiment 8, wherein the movable manifold boundary is a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet, wherein the driver is configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm.

10. The aspiration modulation device of embodiment 9, wherein the actuator is directly mechanically coupled to the diaphragm.

11. The aspiration modulation device of embodiment 10, wherein the actuator comprises a rod directly mechanically coupled to the diaphragm.

12. The aspiration modulation device of embodiment 10 or embodiment 1 1 , wherein the actuator is removably coupled to the diaphragm.

13. The aspiration modulation device of embodiment 9, wherein the actuator is fluidly coupled to the diaphragm.

14. The aspiration modulation device of embodiment 9, wherein the pressure transduction element is a secondary pressure transduction element, and wherein the fluid pressure oscillator further comprises a primary pressure transduction element fluidly coupled to the secondary pressure transduction element.

15. The aspiration modulation device of embodiment 14, wherein the primary pressure transduction element is a piston, and wherein the actuator com prises a piston shaft mechanically coupled to the piston.

16. The aspiration modulation device of embodiment 15, wherein the manifold cavity comprises a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the diaphragm is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber, wherein the working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid.

17. The aspiration modulation device of embodiment 14, wherein the secondary pressure transduction element is a diagram, and primary pressure transduction element is another diaphragm.

18. The aspiration modulation device of embodiment 14, wherein the primary pressure transduction element is contained within the manifold cavity.

19. The aspiration modulation device of embodiment 14, wherein the primary pressure transduction element is external to the manifold cavity.

20. The aspiration modulation device of embodiment 19, further comprising a flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

21 . The aspiration modulation device of embodiment 7, wherein the actuator is a linear actuator, and the driver is configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

22. The aspiration modulation device of embodiment 21 , wherein the actuator is a voice coil actuator.

23. The aspiration modulation device of any of embodiments 7-22, wherein the driver is an electrical driver.

24. The aspiration modulation device of embodiment 1 , further comprising another pressure oscillator, wherein the fluid pressure oscillator and the other pressure oscillator are configured for concurrently and independently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform.

25. The aspiration modulation device of embodiment 24, wherein the desired modulated pressure waveform is a desired modulated complex pressure waveform having at least two different base frequencies.

26. The aspiration modulation device of any of embodiments 1 -25, wherein the controller is configured for selecting one of a plurality of different modulated therapeutic pressure waveforms, and wherein the waveform signal that is dynamically modified in response to the measured parameter corresponds to the selected one modulated therapeutic waveform.

27. The aspiration modulation device of embodiment 26, further comprising a user interface configured for receiving user input selecting the one modulated therapeutic waveform.

28. The aspiration modulation device of any of embodiments 1-25, wherein the controller is further configured for generating a plurality of waveform signals respectively corresponding to a plurality of different modulated diagnostic pressure waveforms, wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber sequentially in accordance with the plurality of waveform signals, thereby modulating the vacuum pressure within the pressure chamber; the aspiration modulation device further comprising a processor configured for analyzing the measured parameter in response to the modulation of the vacuum pressure within the pressure chamber, and generating or selecting the modulated therapeutic pressure waveform based on the analysis of the measured parameter.

29. The aspiration modulation device of embodiment 28, wherein the plurality of different modulated diagnostic pressure waveforms respectively have different frequencies.

30. The aspiration modulation device of embodiment 28 or embodiment 29, wherein the controller, in response to a thrombus clogging the aspiration catheter, is configured for generating the plurality of waveform signals; and

'wherein the processor is configured for determining one or more characteristics of the thrombus based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined one or more characteristics of the thrombus.

31 . The aspiration modulation device of embodiment 28 or embodiment 29, wherein the controller, when the aspiration catheter is connected to the aspiration modulation device, is configured for generating the plurality of waveform signals; and wherein the processor is configured for determining a type of the aspiration catheter based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined type of the aspiration catheter.

32. The aspiration modulation device of any of embodiments 1-31 , further comprising: a master unit comprising a first casing containing the controller; and a slave unit comprising a second casing containing the pressure manifold and at least a portion of the fluid pressure oscillator.

33. The aspiration modulation device of embodiment 31 , further comprising flexible fluidic tubing fluidly coupling the master unit and slave unit to each other.

34. The aspiration modulation device of embodiment 32, wherein the master unit is configured for being inserted into the second casing of the slave unit.

35. The aspiration modulation device of embodiment 34, wherein the master unit is configured for being electrically coupled to the slave unit when inserted into the second casing of the slave unit.

36. The aspiration modulation device of any of embodiments 1 -35, wherein the fluid pressure modulated by the fluid pressure oscillator is a baseline vacuum pressure applied by the vacuum source to the pressure chamber.

37. An aspiration system, comprising: the aspiration modulation device of any of embodiments 1-36; the vacuum source; and the aspiration catheter.

38. An aspiration modulation device for use with an aspiration catheter and a vacuum source, comprising: a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber; and a fluid pressure oscillator comprising a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet, the fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm, thereby modulating a vacuum pressure within the pressure chamber.

39. The aspiration modulation device of embodiment 38, further comprising a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform, wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm in accordance with the waveform signal, thereby modulating the vacuum pressure within the pressure chamber.

40. The aspiration modulation device of embodiment 39, further comprising a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, wherein the controller is configured for, in response to the measured parameter, dynamically modifying the waveform signal, and wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the diaphragm in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

41. The aspiration modulation device of any of embodiments 38-40, wherein the fluid pressure oscillator further comprises: an actuator configured for being operably coupled to the diaphragm; and a driver configured for controlling the actuator to flex the diaphragm in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber.

42. The aspiration modulation device of embodiment 41 , wherein the actuator is directly mechanically coupled to the diaphragm.

43. The aspiration modulation device of embodiment 42, wherein the actuator comprises a rod directly mechanically coupled to the diaphragm.

44. The aspiration modulation device of embodiment 42 or embodiment 43, wherein the actuator is removably coupled to the diaphragm. 45. The aspiration modulation device of embodiment 41 , wherein the actuator is fluidly coupled to the diaphragm.

46. The aspiration modulation device of embodiment 41 , wherein the diaphragm is a secondary pressure transduction element, and wherein the fluid pressure oscillator further comprises a primary pressure transduction element fluidly coupled to the secondary pressure transduction element.

47. The aspiration modulation device of embodiment 46, wherein the fluid pressure oscillator further comprises a piston, and wherein the actuator comprises a piston shaft mechanically coupled to the piston, and wherein the actuator is fluidly coupled to the diaphragm via the piston.

48. The aspiration modulation device of embodiment 47, wherein the manifold cavity comprises a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the secondary pressure transduction element is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber, wherein the working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid.

49. The aspiration modulation device of embodiment 46, wherein the primary pressure transduction element is another diaphragm.

50. The aspiration modulation device of embodiment 46, wherein the primary pressure transduction element is contained within the manifold cavity.

51. The aspiration modulation device of embodiment 46, wherein the primary pressure transduction element is external to the manifold cavity.

52. The aspiration modulation device of embodiment 51 , further comprising flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

53. The aspiration modulation device of embodiment 41 , wherein the actuator is a linear actuator, and the driver is configured for controlling the actuator to flex the diaphragm in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

54. The aspiration modulation device of embodiment 53, wherein the actuator is a voice coil actuator.

55. The aspiration modulation device of any of embodiments 41-54, wherein the driver is an electrical driver. 56. The aspiration modulation device of embodiment 38, further comprising another pressure oscillator comprising another diaphragm affixed within the manifold cavity in opposition to the diaphragm, such that the manifold cavity is divided between the pressure chamber between the opposing diaphragms, and working chambers external to the opposing diaphragms that are fluidly isolated from the vacuum inlet and the vacuum outlet, wherein the fluid pressure oscillator and the other pressure oscillator are configured for concurrently and independently oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the respective diaphragms, thereby modulating the vacuum pressure within the pressure chamber.

57. The aspiration modulation device of any of embodiments 38-56, wherein the fluid pressure modulated by the fluid pressure oscillator is a baseline vacuum pressure applied by the vacuum source to the pressure chamber.

58. A dynamic aspiration system, comprising: the aspiration modulation device of any of embodiments 38-57; the vacuum source; and the aspiration catheter.

59. An aspiration modulation device for use with an aspiration catheter and a vacuum source, comprising: a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber; and a plurality of fluid pressure oscillators configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating a vacuum pressure within the pressure chamber.

60. The aspiration modulation device of embodiment 59, wherein the plurality of fluid pressure oscillators is configured for independently oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber.

61. The aspiration modulation device of embodiment 59, further comprising a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform, wherein the plurality of fluid pressure oscillators are configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the waveform signal, thereby modulating the vacuum pressure within the pressure chamber.

62. The aspiration modulation device of embodiment 61 , further comprising a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, wherein the controller is configured for, in response to the measured parameter, dynamically modifying the waveform signal, and wherein the plurality of fluid pressure oscillators are configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

63. The aspiration modulation device of embodiment 61 , wherein the waveform signal corresponds to a complex pressure waveform having at least two different base frequencies.

64. The aspiration modulation device of any of embodiments 59-63, wherein each of the plurality of fluid pressure oscillators further comprises: a pressure transduction element configured for interfacing with the pressure modulating fluid within the pressure chamber; an actuator configured for being operably coupled to the pressure transduction element; and a driver configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber.

65. The aspiration modulation device of embodiment 64, wherein the pressure transduction element of the respective each fluid pressure oscillator comprises a diaphragm affixed within the manifold cavity.

66. The aspiration modulation device of embodiment 65, wherein the diaphragms of two of the plurality of fluid pressure oscillators oppose each other, such that the manifold cavity is divided between the pressure chamber between the opposing diaphragms, and working chambers external to the opposing diaphragms that are fluidly isolated from the vacuum inlet and the vacuum outlet, wherein two fluid pressure oscillators are configured for concurrently oscillating the variable volume of the pressure modulating fluid within the pressure chamber via the respective diaphragms, thereby modulating the vacuum pressure within the pressure chamber.

67. The aspiration modulation device of embodiment 65, wherein the actuator of the respective each fluid pressure oscillator is directly coupled to the diaphragm of the respective each fluid pressure oscillator.

68. The aspiration modulation device of embodiment 67, wherein the actuator of the respective each fluid pressure oscillator comprises a rod directly mechanically coupled to the diaphragm of the respective each fluid pressure oscillator.

69. The aspiration modulation device of embodiment 67 or embodiment 68, wherein the actuator of the respective each fluid pressure oscillator is removably coupled to the diaphragm of the respective each fluid pressure oscillator.

70. The aspiration modulation device of embodiment 65, wherein the actuator of the respective each fluid pressure oscillator is fluidly coupled to the diaphragm of the respective each fluid pressure oscillator.

71. The aspiration modulation device of embodiment 65, wherein the actuator of the respective each fluid pressure oscillator is a linear actuator, and the driver of the respective each fluid pressure oscillator is configured for controlling the actuator of the respective each fluid pressure oscillator to flex the diaphragm of the respective each fluid pressure oscillator in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

72. The aspiration modulation device of embodiment 71 , wherein the actuator of the respective each fluid pressure oscillator is a voice coil actuator.

73. The aspiration modulation device of any of embodiments 64-72, wherein the driver of the respective each fluid pressure oscillator is an electrical driver.

74. The aspiration modulation device of any of embodiments 59-73, wherein the fluid pressure modulated by the fluid pressure oscillator is a baseline vacuum pressure applied by the vacuum source to the pressure chamber.

75. A dynamic aspiration system, comprising: the aspiration modulation device of any of embodiments 59-74; the vacuum source; and the aspiration catheter.

76. An aspiration modulation device for use with an aspiration catheter, a vacuum source, and a pressurized fluid source, comprising: a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber, and a vent inlet configured for fluidly coupling the pressurized fluid source to the pressure chamber; a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating a vacuum pressure within the pressure chamber; and a fluid refill control element configured for selectively fluidly coupling the pressurized fluid source to the pressure chamber.

77. The aspiration modulation device of embodiment 76, wherein, when a fluid pressure within the pressure chamber drops below a threshold fluid pressure, the fluid refill control element is configured for conveying pressure modulating fluid from the pressurized fluid source into the pressure chamber.

78. The aspiration modulation device of embodiment 76 or embodiment 77, wherein the fluid refill control element is a check valve.

79. The aspiration modulation device of any of embodiments 76-78, wherein the pressurized fluid source is at atmospheric pressure.

80. The aspiration modulation device of any of embodiments 76-79, further comprising a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform, wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the waveform signal, thereby modulating the vacuum pressure within the pressure chamber.

81. The aspiration modulation device of embodiment 80, further comprising a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, wherein the controller is configured for, in response to the measured parameter, dynamically modifying the waveform signal, and wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

82. The aspiration modulation device of any of embodiments 76-81 , wherein the fluid pressure oscillator comprises: a pressure transduction element configured for interfacing with the pressure modulating fluid within the pressure chamber; an actuator configured for being operably coupled to the pressure transduction element; and a driver configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform.

83. The aspiration modulation device of embodiment 82, wherein the pressure transduction element comprises a movable manifold boundary, and wherein the driver is configured for controlling the actuator to reciprocatably move the movable manifold boundary.

84. The aspiration modulation device of embodiment 83, wherein the movable manifold boundary is a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet, wherein the driver is configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm.

85. The aspiration modulation device of any of embodiments 82-84, wherein the actuator is a linear actuator, and the driver is configured for controlling the actuator to flex the diaphragm in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

86. The aspiration modulation device of embodiment 85, wherein the actuator is a voice coil actuator.

87. The aspiration modulation device of any of embodiments 82-86, wherein the driver is an electrical driver.

88. The aspiration modulation device of any of embodiments 76-87, wherein the fluid pressure modulated by the fluid pressure oscillator is a baseline vacuum pressure applied by the vacuum source to the pressure chamber.

89. A dynamic aspiration system, comprising: the aspiration modulation device of any of embodiments 76-88; the vacuum source; and the aspiration catheter. 90. An aspiration modulation device for use with an aspiration catheter and a vacuum source, comprising: a controller configured for outputting a waveform signal corresponding to a modulated therapeutic pressure waveform; a pressure manifold comprising a manifold cavity having a pressure chamber configured for containing a variable volume of pressure modulating fluid, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber; a fluid pressure oscillator configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the waveform signal, thereby modulating a vacuum pressure within the pressure chamber; a master unit comprising a casing carrying the controller; and a slave unit comprising a casing carrying at least a portion of the pressure manifold and at least a portion of the fluid pressure oscillator, wherein the master unit is configured for being operably coupled to and operably decoupled from the slave unit.

91. The aspiration modulation device of embodiment 90, further comprising a sensor carried by the slave unit and configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, wherein the controller is configured for, in response to the measured parameter, dynamically modifying the waveform signal, and wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, such that the fluid pressure at the distal end of the aspiration catheter tracks a desired modulated pressure waveform.

92. The aspiration modulation device of embodiment 90 or embodiment 91 , wherein the casing of the master unit carries at least another portion of the fluid pressure oscillator.

93. The aspiration modulation device of embodiment 92, wherein the fluid pressure oscillator comprises: a pressure transduction element carried by the slave unit and configured for interfacing with the pressure modulating fluid within the pressure chamber; an actuator configured for being operably coupled to the pressure transduction element; and a driver configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform; wherein the pressure transduction element is carried by the casing of the slave unit; and wherein the driver is carried by the casing of the master unit.

94. The aspiration modulation device of embodiment 93, wherein the actuator is carried by the casing of the master unit.

95. The aspiration modulation device of embodiment 94, wherein the respective casings of the master unit and the slave unit are casing portions that are mechanically affixed directly to each other to form a single casing.

96. The aspiration modulation device of any of embodiments 92-95, wherein the pressure transduction element comprises a movable manifold boundary, and wherein the driver is configured for controlling the actuator to reciprocatably move the movable manifold boundary.

97. The aspiration modulation device of embodiment 96, wherein the movable manifold boundary is a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet, wherein the driver is configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm.

98. The aspiration modulation device of embodiment 97, wherein the actuator is directly mechanically coupled to the diaphragm.

99. The aspiration modulation device of embodiment 98, wherein the actuator comprises a rod directly mechanically coupled to the diaphragm.

100. The aspiration modulation device of embodiment 98 or embodiment 99, wherein the actuator is removably coupled to the diaphragm.

101 . The aspiration modulation device of embodiment 99, wherein the pressure transduction element is a secondary pressure transduction element contained within the manifold cavity, and wherein the fluid pressure oscillator further comprises a primary pressure transduction element carried by the casing portion of the master unit and fluidly coupled to the secondary pressure transduction element.

102. The aspiration modulation device of embodiment 101 , wherein the primary pressure transduction element is a piston, and wherein the actuator com prises a piston shaft mechanically coupled to the piston.

103. The aspiration modulation device of embodiment 102, wherein the manifold cavity comprises a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the diaphragm is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber, wherein the working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid.

104. The aspiration modulation device of any of embodiments 93-103, wherein the pressure transduction element is a secondary pressure transduction element contained within the manifold cavity, and wherein the fluid pressure oscillator further comprises a primary pressure transduction element carried by the casing of the master unit, the aspiration modulation device further comprising flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

105. The aspiration modulation device of embodiment 93, wherein the actuator is a linear actuator, and the driver is configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

106. The aspiration modulation device of embodiment 105, wherein the actuator is a voice coil actuator.

107. The aspiration modulation device of any of embodiments 90-106, wherein the driver is an electrical driver.

108. The aspiration modulation device of embodiment 90-103, wherein the master unit is configured for being inserted into the slave unit.

109. The aspiration modulation device of any of embodiments 90-108, wherein the fluid pressure modulated by the fluid pressure oscillator is a baseline vacuum pressure applied by the vacuum source to the pressure chamber.

110. A dynamic aspiration system, comprising: the aspiration modulation device of any of embodiments 90-109; the vacuum source; and the aspiration catheter.

111. An aspiration device for use with an aspiration catheter and a vacuum source, comprising: a pressure manifold comprising a manifold cavity having a pressure chamber and a working chamber, a vacuum outlet configured for fluidly coupling the vacuum source to the pressure chamber, and a vacuum inlet configured for fluidly coupling the aspiration catheter to the pressure chamber; and a diaphragm affixed within the manifold cavity for fluidly isolating the pressure chamber from the working chamber, the diaphragm configured for applying a clog clearing pressure to aspiration fluid contained in the pressure chamber in response to a force applied to the diaphragm from the working chamber.

112. The aspiration device of embodiment 111 , wherein the vacuum outlet is configured for fluidly coupling the vacuum source to the pressure chamber during the application of the clog clearing pressure by the diaphragm to the aspiration fluid contained in the pressure chamber.

113. The aspiration device of embodiment 112, wherein the aspiration fluid contained in the pressure chamber is a pressure modulating fluid having a variable volume, the aspiration device further comprising a fluid pressure oscillator configured for applying an oscillatory force to the diaphragm, and wherein the diaphragm is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber in response to the oscillatory force applied to the diaphragm, thereby modulating a vacuum pressure within the pressure chamber.

114. The aspiration device of embodiment 111 , wherein the diaphragm is further configured for fluidly decoupling the vacuum source from the pressure chamber by sealing the vacuum outlet prior to the application of the clog clearing pressure by the diaphragm to the aspiration fluid contained in the pressure chamber.

115. The aspiration device of embodiment 1 14, wherein the diaphragm has a sealing region configured for contacting the vacuum outlet to seal the vacuum outlet from the pressure chamber, and a deflectable region configured for deflecting within the pressure chamber to apply the clog clearing pressure to the aspiration fluid contained in the pressure chamber.

116. The aspiration device of embodiment 115, wherein the sealing region is a center circular region of the diaphragm, and the deflectable region is an annular region of the diaphragm. 117. The aspiration device of any of embodiments 114-116, wherein the diaphragm is configured for sealing the vacuum outlet from the pressure chamber in response to a pressure in the working chamber greater than a sealing pressure threshold.

118. The aspiration device of embodiment 117, wherein the diaphragm is configured for applying the clog clearing pressure to the aspiration fluid contained in the pressure chamber in a dedicated manner.

119. The aspiration device of embodiment 117 or embodiment 118, wherein the diaphragm is further configured for fluidly recoupling the vacuum source to the pressure chamber by unsealing the vacuum outlet in response to a pressure in the working chamber less than an unsealing pressure threshold.

120. The aspiration device of embodiment 119, wherein the unsealing pressure threshold is less than the sealing pressure threshold when the aspiration catheter remains clogged with a thrombus.

121. The aspiration device of embodiment 119, wherein the unsealing pressure threshold is greater than the sealing pressure threshold when a thrombus in the aspiration catheter is cleared.

122. The aspiration device of any of embodiments 119-121 , further comprising a spring configured for biasing the diaphragm to unseal the vacuum outlet from the pressure chamber.

123. The aspiration device of any of embodiments 119-121 , wherein the diaphragm has a passive restorative force for biasing the diaphragm to unseal the vacuum outlet from the pressure chamber.

124. The aspiration device of any of embodiments 119-123, wherein the clog clearing pressure that the diaphragm is configured for applying to the aspiration fluid contained in the pressure chamber is a pressure pulse output, and wherein the diaphragm is configured for applying the pressure pulse output to the aspiration fluid contained in the pressure chamber in response to a pressure pulse input applied to a working fluid contained in the working chamber, wherein a pressure of a peak magnitude of the pressure pulse input is above the sealing pressure threshold.

125. The aspiration device of embodiment 124, wherein the diaphragm is configured for coupling the vacuum source to the pressure chamber in response to a removal of the pressure pulse input from the working fluid contained in the working chamber, wherein a pressure of a base magnitude of the pressure pulse input is below the unsealing pressure threshold.

126. The aspiration device of embodiment 124, wherein the diaphragm is configured for maintaining the decoupling of the vacuum source from the pressure chamber in response to a removal of the pressure pulse input from the working fluid contained in the working chamber, wherein a pressure of a base magnitude of the pressure pulse input is above the unsealing pressure threshold.

127. The aspiration device of any of embodiments 124-126, further comprising a pressure control device configured for applying the pressure pulse input to the working fluid contained in the working chamber.

128. The aspiration device of embodiment 127, wherein the pressure control device comprises a three-way valve configured for applying the pressure pulse input to the working fluid contained in the working chamber by alternately fluidly coupling the working chamber to atmosphere and another vacuum source.

129. The aspiration device of embodiment 127, wherein the pressure control device comprises a pressure generator configured for applying the pressure pulse input to the working fluid contained in the working chamber by generating the pressure pulse input.

130. The aspiration device of any of embodiments 127-129, further comprising a sensor configured for measuring a parameter indicative of a fluid pressure at the distal end of the aspiration catheter, wherein the pressure control device is configured for applying the pressure pulse input to the working fluid contained in the working chamber in response to the measured parameter.

131. The aspiration device of any of embodiments 124-130, wherein the diaphragm is configured for modulating the pressure pulse input, such that the pressure pulse output corresponds to the modulated pressure pulse input.

132. The aspiration device of any of embodiments 124-131 , wherein the clog clearing pressure that the diaphragm is configured for applying to the aspiration fluid contained in the pressure chamber is a series of pressure pulse outputs, wherein the diaphragm is configured for applying the series of pressure pulse outputs to the aspiration fluid contained in the pressure chamber in response to the series of pressure pulse inputs applied by the pressure control device to the working fluid contained in the working chamber. 133. A dynamic aspiration system, comprising: the aspiration device of any of embodiments 111-132; the vacuum source; and the aspiration catheter.

Claims

CLAIMS What is claimed is:

2. The aspiration modulation device of claim 1 , wherein the pressure manifold further has a vent inlet configured for fluidly coupling a pressurized fluid source to the pressure chamber, the aspiration modulation device further comprising a fluid refill control element configured for selectively fluidly coupling the pressurized fluid source to the pressure chamber.

3. The aspiration modulation device of claim 2, wherein, when a fluid pressure within the pressure chamber drops below a threshold fluid pressure, the fluid refill control element is configured for conveying pressure modulating fluid from the pressurized fluid source into the pressure chamber.

4. The aspiration modulation device of any of claims 1-3, wherein the sensor is a force feedback sensor configured for measuring a force output of the fluid pressure oscillator.

5. The aspiration modulation device of any of claims 1-3, wherein the sensor is a pressure sensor.

6. The aspiration modulation device of claim 5, wherein the pressure sensor is configured for measuring a fluid pressure within the pressure chamber.

7. The aspiration modulation device of any of claims 1-6, wherein the fluid pressure oscillator comprises: a pressure transduction element configured for interfacing with the pressure modulating fluid within the pressure chamber; an actuator configured for being operably coupled to the pressure transduction element; and a driver configured for controlling the actuator to physically move the pressure transduction element in a manner that oscillates the variable volume of the pressure modulating fluid within the pressure chamber, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform.

8. The aspiration modulation device of claim 7, wherein the pressure transduction element comprises a movable manifold boundary, and wherein the driver is configured for controlling the actuator to reciprocatably move the movable manifold boundary.

9. The aspiration modulation device of claim 8, wherein the movable manifold boundary is a diaphragm affixed within the manifold cavity, thereby dividing the manifold cavity into the pressure chamber and a working chamber fluidly isolated from the vacuum inlet and the vacuum outlet, wherein the driver is configured for controlling the actuator to physically move the diaphragm by flexing the diaphragm.

10. The aspiration modulation device of claim 9, wherein the actuator is directly mechanically coupled to the diaphragm.

11. The aspiration modulation device of claim 10, wherein the actuator comprises a rod directly mechanically coupled to the diaphragm.

12. The aspiration modulation device of claim 10 or claim 11 , wherein the actuator is removably coupled to the diaphragm.

13. The aspiration modulation device of claim 9, wherein the actuator is fluidly coupled to the diaphragm.

14. The aspiration modulation device of claim 9, wherein the pressure transduction element is a secondary pressure transduction element, and wherein the fluid pressure oscillator further comprises a primary pressure transduction element fluidly coupled to the secondary pressure transduction element.

15. The aspiration modulation device of claim 14, wherein the primary pressure transduction element is a piston, and wherein the actuator comprises a piston shaft mechanically coupled to the piston.

16. The aspiration modulation device of claim 15, wherein the manifold cavity comprises a reduced diameter cylinder in which the piston is reciprocatably disposed, and an increased diameter cylinder in which the diaphragm is affixed, such that the increased diameter cylinder is divided between the pressure chamber and the working chamber, wherein the working chamber contains a primary pressure modulating fluid, and the pressure modulating fluid contained in the pressure chamber is a secondary pressure modulating fluid.

17. The aspiration modulation device of claim 14, wherein the secondary pressure transduction element is a diagram, and primary pressure transduction element is another diaphragm.

18. The aspiration modulation device of claim 14, wherein the primary pressure transduction element is contained within the manifold cavity.

19. The aspiration modulation device of claim 14, wherein the primary pressure transduction element is external to the manifold cavity.

20. The aspiration modulation device of claim 19, further comprising a flexible fluidic tubing fluidly coupling the primary pressure transduction element to the secondary pressure transduction element.

21 . The aspiration modulation device of claim 7, wherein the actuator is a linear actuator, and the driver is configured for controlling the actuator to physically move the pressure transduction element in a manner that reciprocatably varies the variable volume of the pressure modulating fluid within the pressure chamber.

22. The aspiration modulation device of claim 21 , wherein the actuator is a voice coil actuator.

23. The aspiration modulation device of any of claims 7-22, wherein the driver is an electrical driver.

24. The aspiration modulation device of claim 1 , further comprising another pressure oscillator, wherein the fluid pressure oscillator and the other pressure oscillator are configured for concurrently and independently oscillating the variable volume of the pressure modulating fluid within the pressure chamber in accordance with the dynamically modified waveform signal, thereby modulating the vacuum pressure within the pressure chamber, such that the fluid pressure at the distal end of the aspiration catheter tracks the desired modulated pressure waveform.

25. The aspiration modulation device of claim 24, wherein the desired modulated pressure waveform is a desired modulated complex pressure waveform having at least two different base frequencies.

26. The aspiration modulation device of any of claims 1-25, wherein the controller is configured for selecting one of a plurality of different modulated therapeutic pressure waveforms, and wherein the waveform signal that is dynamically modified in response to the measured parameter corresponds to the selected one modulated therapeutic waveform.

27. The aspiration modulation device of claim 26, further comprising a user interface configured for receiving user input selecting the one modulated therapeutic waveform.

28. The aspiration modulation device of any of claims 1-25, wherein the controller is further configured for generating a plurality of waveform signals respectively corresponding to a plurality of different modulated diagnostic pressure waveforms, wherein the fluid pressure oscillator is configured for oscillating the variable volume of the pressure modulating fluid within the pressure chamber sequentially in accordance with the plurality of waveform signals, thereby modulating the vacuum pressure within the pressure chamber; the aspiration modulation device further comprising a processor configured for analyzing the measured parameter in response to the modulation of the vacuum pressure within the pressure chamber, and generating or selecting the modulated therapeutic pressure waveform based on the analysis of the measured parameter.

29. The aspiration modulation device of claim 28, wherein the plurality of different modulated diagnostic pressure waveforms respectively have different frequencies.

30. The aspiration modulation device of claim 28 or claim 29, wherein the controller, in response to a thrombus clogging the aspiration catheter, is configured for generating the plurality of waveform signals; and

31 . The aspiration modulation device of claim 28 or claim 29, wherein the controller, when the aspiration catheter is connected to the aspiration modulation device, is configured for generating the plurality of waveform signals; and wherein the processor is configured for determining a type of the aspiration catheter based on the analysis of the measured parameter, and generating or selecting the modulated therapeutic pressure waveform based on the determined type of the aspiration catheter.

32. The aspiration modulation device of any of claims 1-31 , further comprising: a master unit comprising a first casing containing the controller; and a slave unit comprising a second casing containing the pressure manifold and at least a portion of the fluid pressure oscillator.

33. The aspiration modulation device of claim 31 , further comprising flexible fluidic tubing fluidly coupling the master unit and slave unit to each other.

34. The aspiration modulation device of claim 32, wherein the master unit is configured for being inserted into the second casing of the slave unit.

35. The aspiration modulation device of claim 34, wherein the master unit is configured for being electrically coupled to the slave unit when inserted into the second casing of the slave unit.

36. The aspiration modulation device of any of claims 1-35, wherein the fluid pressure modulated by the fluid pressure oscillator is a baseline vacuum pressure applied by the vacuum source to the pressure chamber.

37. An aspiration system, comprising: the aspiration modulation device of any of claims 1-36; the vacuum source; and the aspiration catheter.