[go: up one dir, main page]

WO2020152628A2 - Dispositif d'accès à un tissu - Google Patents

Dispositif d'accès à un tissu Download PDF

Info

Publication number
WO2020152628A2
WO2020152628A2 PCT/IB2020/050543 IB2020050543W WO2020152628A2 WO 2020152628 A2 WO2020152628 A2 WO 2020152628A2 IB 2020050543 W IB2020050543 W IB 2020050543W WO 2020152628 A2 WO2020152628 A2 WO 2020152628A2
Authority
WO
WIPO (PCT)
Prior art keywords
projections
access device
tissue
tissue access
projection
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2020/050543
Other languages
English (en)
Other versions
WO2020152628A3 (fr
Inventor
Jorge Mario HERRERA MORALES
John Donoghue
Luc Stoppini
Aleksander SOBOLEWSKI
Alain Woodtli
Marc HEUSCHKEL
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Haute Ecole Du Paysage D'ingenierie Et D'architecture De Geneve Hepia
Wyss Center for Bio and Neuro Engineering
Original Assignee
Haute Ecole Du Paysage D'ingenierie Et D'architecture De Geneve Hepia
Wyss Center for Bio and Neuro Engineering
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Haute Ecole Du Paysage D'ingenierie Et D'architecture De Geneve Hepia, Wyss Center for Bio and Neuro Engineering filed Critical Haute Ecole Du Paysage D'ingenierie Et D'architecture De Geneve Hepia
Publication of WO2020152628A2 publication Critical patent/WO2020152628A2/fr
Publication of WO2020152628A3 publication Critical patent/WO2020152628A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/685—Microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6867—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive specially adapted to be attached or implanted in a specific body part
    • A61B5/6868—Brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/04—Arrangements of multiple sensors of the same type
    • A61B2562/046—Arrangements of multiple sensors of the same type in a matrix array
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14503—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using microdialysis
    • A61B5/14528—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using microdialysis invasively
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A61B5/14735—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter comprising an immobilised reagent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/369—Electroencephalography [EEG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0529—Electrodes for brain stimulation
    • A61N1/0531—Brain cortex electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0529—Electrodes for brain stimulation
    • A61N1/0534—Electrodes for deep brain stimulation

Definitions

  • Embodiments of the present disclosure relate generally to neural interface systems, and in particular neural interface systems that include implantable devices configured to record or modulate physiologic activity of a subject for extended periods of time.
  • Implantable sensors for subjects exhibit numerous limitations, including limited implant lifetime during which sensing can be reliably performed.
  • Current failure modes of current devices are of both biotic nature and abiotic nature. Some of the failure modes include delamination, degradation, dissolution, rupture, and cracking.
  • a device for accessing tissue of a subject including: a substrate including a top side and a bottom side; one or more projections extending from the bottom side of the substrate, each projection including a shaft portion, wherein the shaft portion includes a distal portion, and wherein the distal portion includes a distal end; wherein each projection is configured to transfer energy, signals, and/or material to and/or from the subject tissue.
  • a neural interface system for a subject including: a tissue access device according to the previous aspect of the disclosure; a processing unit configured to receive data from the tissue access device; and a conduit operably connecting the tissue access device to the processing unit.
  • a device for accessing tissue of a subject includes a substrate having a top side and a bottom side.
  • the device also includes one or more projections extending from the bottom side of the substrate.
  • Each projection includes an exterior wall portion defining therein an interior shaft portion.
  • the substrate and the one or more projections are formed from a monolithic mass.
  • the one or more projections are functionalized to enable transfer, between the subject tissue and the substrate, of at least one of an energy, a signal, a material, and a compound.
  • the substrate and one or more projections with their respective interior shaft portions are formed from the monolithic mass by using a freely moving micrometric laser spot and chemical etching process, wherein the freely moving micrometric laser spot is produced by a femtosecond laser system and is focused into the monolithic mass to modify its properties with a high degree of precision where it is desirable to remove portions of the monolithic mass by a subsequent chemical etching process.
  • the flexibility of this example process enables example embodiments to include projections having a variety of shapes, lengths, or functions for example. This is unlike a Utah Array implantable sensor, in which projections can be arranged only in straight lines, with an identical shape for all projections.
  • the one or more projections may be functionalized via one or more respective cores positioned within respective interior shaft portions.
  • the one or more respective cores may be formed of metal microwires inserted into interior shaft portions of the one or more projections.
  • Each of the one or more projections may include a proximal end contiguous with the bottom side of the substrate and a distal end, and the respective inserted metal microwires may be laser welded or arc-welded to the respective projections at the proximal ends or the distal ends thereof.
  • the one or more respective cores may be formed from a fluid precursor material.
  • the one or more respective cores may be formed of glass-like carbon (GLC) or related variants thereof, noble metals, conductive polymers, conductive fluids, or
  • the device may further include one or more lumens lining one or more respective interior shaft portions of the one or more respective projections.
  • the interior shaft portion of each of the one or more projections may be a laser-exposed, chemically etched portion.
  • the device may be biocompatible, biostable, and sterilizable, and the one or more projections may have a size, shape, and pitch that allow the device to be implanted into the subject tissue. In one example, the device has a size, shape, and pitch that allow the device to be inserted through the skin.
  • the one or more projections may include at least 1, at least 2, at least 4, at least 8, or at least 9 projections.
  • a projection may be a deep brain stimulation (DBS) electrode.
  • Projections may each be characterized by a length of no more than 1.0mm, no more than 1.5mm, no more than 2.0mm, or no more than 300mm.
  • the one or more projections may include at least one projection with a lateral extension, through the exterior wall portion of the projection, on or proximate to a distal end of the projection, a proximal end of the projection being proximate to the bottom side of the substrate.
  • a method of manufacturing a tissue access device for accessing tissue of a subject includes forming, from a monolithic mass, a substrate and one or more projections.
  • the substrate includes a top side and a bottom side, and the projection(s) extend from the bottom side of the substrate.
  • Each projection includes an exterior wall portion defining therein an interior shaft portion.
  • the method further includes functionalizing the one or more projections, thereby enabling transfer, between the subject tissue and the substrate, of at least one of an energy, a signal, a material, and a compound.
  • Functionalizing the one or more projections may include positioning cores within the interior shaft portions of the one or more projections. Positioning cores may further include inserting metal microwires into interior shaft portions of the one or more projections. Each of the one or more projections may include a proximal end contiguous with the bottom side of the substrate and a distal end. Positioning the cores may further include laser welding the metal microwires to the respective projections at the proximal ends or at the distal ends thereof. Positioning cores can include injecting a fluid precursor material into the one or more projections and forming glass-like carbon (GLC) and related variants, noble metals, conductive polymers or conductive fluid cores. Functionalizing the one or more projections can include centrifuging the substrate and the multiple projections.
  • LLC glass-like carbon
  • Forming the one or more projections can include laser-exposing and chemically etching portions of the monolithic mass that are within the interior shaft portion of each of the one or more projections.
  • Functionalizing the one or more projections may ensure a hermetic and biostable interface between the cores and the interior shaft portions of the one or more projections.
  • FIG. 1 A is a cross-sectional illustration of a monolithic mass from which an embodiment tissue access device may be formed
  • FIG. IB is a schematic illustration of an embodiment tissue access device interacting with subject tissue
  • FIG. 1C is a schematic illustration of an embodiment of a neural interface system including an implantable device (an example of an embodiment“tissue access device”) and a processing unit, consistent with the disclosure;
  • FIG. ID is a bottom-view illustration of the embodiment implantable device illustrated in FIG. 1C, including a 10 by 10 array of projections;
  • FIG. 2 illustrates a flow chart of a representative method for manufacturing an implantable device of a neural interface system
  • FIGS. 3A-3D are cross-sectional illustrations of a projection that can form part of an embodiment tissue access device, particularly illustrating how the projection may be functionalized using a microwire core and a laser or arc welding process;
  • FIGS. 4A-4D are cross-sectional illustrations showing various stages of functionalizing a glass capillary projection array to form a tissue access device, particularly by using a fluid precursor material process to form projection cores;
  • FIGS. 4E-4F are perspective-view illustrations of a centrifugation assembly that may be used to functionalize the glass capillary projection array illustrated in FIG. 4 A according to the process illustrated in FIGS. 4A-4D;
  • FIGS. 5A-5C are perspective-view illustrations of various electrode projections that can form part of embodiment tissue access devices;
  • FIG. 6 is a flow diagram illustrating an embodiment procedure for manufacturing a tissue access device and embodiment tissue access device.
  • first element when a first element is referred to as being“in,” “on,” and/or“within” a second element, the first element can be positioned: within an internal space of the second element, within a portion of the second element (e.g., within a wall of the second element); positioned on an external and/or internal surface of the second element; and combinations of one or more of these.
  • proximate when used to describe proximity of a first component or location to a second component or location, is to be taken to include one or more locations near to the second component or location, as well as locations in, on and/or within the second component or location.
  • a component positioned proximate an anatomical site e.g., a target tissue location
  • spatially relative terms such as“beneath,”“below,”“lower,”“above,”“upper,” and the like may be used to describe an element and/or feature’s relationship to another element(s) and/or feature(s) as, for example, illustrated in the figures. It will be further understood that the spatially relative terms are intended to encompass different orientations of the device in use and/or operation in addition to the orientation depicted in the figures. For example, if the device in a figure is turned over, elements described as“below” and/or “beneath” other elements or features would then be oriented“above” the other elements or features. The device can be otherwise oriented (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
  • the terms“reduce,”“reducing,”“reduction,” and the like, where used herein, are to include a reduction in a quantity, including a reduction to zero. Reducing the likelihood of an occurrence shall include prevention of the occurrence.
  • the terms “prevent,”“preventing,” and“prevention” shall include the acts of“reduce,”“reducing,” and “reduction,” respectively.
  • the term“and/or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other.
  • “A and/or B” is to be taken as specific disclosure of each of (i) A, (ii) B, and (iii) A and B, just as if each is set out individually herein.
  • the term“one or more,” where used herein can mean one, two, three, four, five, six, seven, eight, nine, ten, or more, up to any number. Thus, this term encompasses“two or more,”“four or more,”“eight or more,” etc.
  • a component, process, and/or other item selected from the group consisting of: A; B; C; and combinations thereof shall include a set of one or more components that comprise: one, two, three or more of item A; one, two, three or more of item B; and/or one, two, three, or more of item C.
  • “and” can mean“or,” and “or” can mean“and.”
  • the feature can have A, B, and C, or any combination of A, B, and C.
  • the feature can have only one or two of A, B, or C.
  • the term“diameter” where used herein to describe a non-circular geometry is to be taken as the diameter of a hypothetical circle approximating the geometry being described.
  • the term“diameter” shall be taken to represent the diameter of a hypothetical circle with the same cross-sectional area as the cross section of the component being described.
  • the term“threshold” refers to a maximum level, a minimum level, and/or range of values correlating to a desired or undesired state.
  • a system parameter is maintained above a minimum threshold, below a maximum threshold within a threshold range of values and/or outside a threshold range of values, to cause a desired effect (e.g., efficacious therapy) and/or to prevent or otherwise reduce (hereinafter “prevent”) an undesired event (e.g., a device and/or clinical adverse event).
  • a system parameter is maintained above a first threshold (e.g., above a first temperature threshold to cause a desired therapeutic effect to tissue) and below a second threshold (e.g., below a second temperature threshold to prevent undesired tissue damage).
  • a first threshold e.g., above a first temperature threshold to cause a desired therapeutic effect to tissue
  • a second threshold e.g., below a second temperature threshold to prevent undesired tissue damage
  • a threshold value is determined to include a safety margin, such as to account for subject variability, system variability, tolerances, and the like.
  • “exceeding a threshold” relates to a parameter going above a maximum threshold, below a minimum threshold, within a range of threshold values and/or outside of a range of threshold values.
  • “room pressure” shall mean pressure of the environment surrounding the systems and devices of the disclosure. Positive pressure includes pressure above room pressure or simply a pressure that is greater than another pressure, such as a positive differential pressure across a fluid pathway component such as a valve. Negative pressure includes pressure below room pressure or a pressure that is less than another pressure, such as a negative differential pressure across a fluid component pathway such as a valve. Negative pressure can include a vacuum but does not imply a pressure below a vacuum.
  • the term“vacuum” can be used to refer to a full or partial vacuum, or any negative pressure as described hereinabove.
  • a functional element is to be taken to include one or more elements constructed and arranged to perform a function.
  • a functional element can include a sensor and/or a transducer.
  • a functional element is configured to deliver energy and/or otherwise treat tissue (e.g., a functional element configured as a treatment element).
  • a functional element e.g., a functional element including a sensor
  • a sensor or other functional element is configured to perform a diagnostic function (e.g., to gather data used to perform a diagnosis).
  • a functional element is configured to perform a therapeutic function (e.g., to deliver therapeutic energy and/or a therapeutic agent).
  • a functional element includes one or more elements constructed and arranged to perform a function selected from the group consisting of: deliver energy; extract energy (e.g., to cool a component); deliver a drug or other agent; manipulate a system component or subject tissue; record or otherwise sense a parameter such as a subject physiologic parameter or a system parameter; and combinations of one or more of these.
  • a functional element can include a fluid and/or a fluid delivery system.
  • a functional element can include a reservoir, such as an expandable balloon or other fluid-maintaining reservoir.
  • transducer where used herein is to be taken to include any component or combination of components that receives energy or any input, and produces an output.
  • a transducer can include an electrode that receives electrical energy, and distributes the electrical energy to tissue (e.g., based on the size of the electrode).
  • a transducer converts an electrical signal into any output, such as light (e.g., a transducer including a light emitting diode or light bulb), sound (e.g., a transducer including a piezo crystal configured to deliver ultrasound energy), pressure, heat energy, cryogenic energy, chemical energy; mechanical energy (e.g., a transducer including a motor or a solenoid), magnetic energy, and/or a different electrical signal (e.g., a Bluetooth or other wireless communication element).
  • a transducer can convert a physical quantity (e.g., variations in a physical quantity) into an electrical signal.
  • a transducer can include any component that delivers energy and/or an agent to tissue, such as a transducer configured to deliver one or more of: electrical energy to tissue (e.g., a transducer including one or more electrodes); light energy to tissue (e.g., a transducer including a laser, light emitting diode and/or optical component such as a lens or prism); mechanical energy to tissue (e.g., a transducer including a tissue manipulating element); sound energy to tissue (e.g., a transducer including a piezo crystal); chemical energy; electromagnetic energy;
  • electrical energy to tissue e.g., a transducer including one or more electrodes
  • light energy to tissue e.g., a transducer including a laser, light emitting diode and/or optical component such as a lens or prism
  • mechanical energy to tissue e.g., a transducer including a tissue manipulating element
  • sound energy to tissue e.g., a transducer including
  • fluid can refer to a liquid, gas, gel, or any flowable material, such as a material which can be propelled through a lumen and/or opening.
  • a neural interface system of the disclosure can include an implantable device that can be positioned in one or more locations within a subject, such as at a location on the surface of tissue, such as brain or other neural tissue.
  • the implantable device can include one or more projections, such as projections including one or more cores that are configured to access tissue, such as to measure, sample, modulate and/or record (“record” herein) physiologic parameters of the subject, such as electrical activity of the subject’s brain and/or other physiologic activity of the subject.
  • the neural interface system can include componentry to receive the recorded subject data from the implantable device, and/or to deliver therapy and/or subject feedback to the implantable device.
  • the recorded subject data can be used by a clinician to treat, diagnose, and/or prognose a medical condition of the subject (e.g., a disease and/or disorder of the subject).
  • the one or more projections of the implantable device can be configured to deliver energy (e.g., electrical energy, light energy, and/or sound energy) and/or an agent (e.g., a pharmaceutical drug) to tissue, such as to provide a therapy to the subject (e.g., electrical or optical stimulation therapy and/or drug therapy), and/or to provide feedback to the subject.
  • energy e.g., electrical energy, light energy, and/or sound energy
  • an agent e.g., a pharmaceutical drug
  • a neural interface of the disclosure is configured to record data and provide a therapy in a closed-loop fashion.
  • a neural interface system of the disclosure is configured as a brain-machine interface, such as to allow a paralyzed subject or other subject to perform thought-control of a computer and/or other controllable device.
  • FIG. 1 A is a cross-sectional illustration of a monolithic mass 113 from which an embodiment tissue access device may be formed.
  • “monolithic mass” should be understood to include any crystalline, polycrystalline, amorphous, glassy, or other solid mass, a portion of which remains intact to form an embodiment tissue access device as other parts are removed.
  • the monolithic mass 113 may include various types of glass, crystals, composites, etc., as noted hereinafter in relation to FIG. 1C.
  • the tissue access device can have high freedom of design (akin to 3D printing) and high spatial resolution with micrometric precision.
  • tissue access device embodiments described herein can be made from a monolithic mass of, for example, glass, and still have flexible projections. Such flexibility of the projection(s) facilitates the implantation of the tissue access devices and increases their sturdiness and longevity.
  • tissue access device embodiments can also be produced from a plane parallel to the base of a wafer substrate, so a tissue access device with very long projection(s) of length close to the diameter of the wafer can be produced.
  • Such long projection(s) can be employed, for example, as Deep Brain Stimulation (DBS) electrode(s).
  • DBS Deep Brain Stimulation
  • FIG. 1 A includes an outline 115 of a tissue access device 100 that is illustrated in FIG. IB.
  • portions of the monolithic mass 113 outside the outline 115 may be removed.
  • An example process for forming an embodiment tissue access device from the monolithic mass 113 includes the Femtoprint® 3D printing technology.
  • a femtosecond laser beam is focused in a laser spot of a few microns in diameter, for example, inside a monolithic piece of material, modifying the material’s properties where the laser spot reaches a certain focused intensity threshold.
  • each of the projections 120 may be a laser- exposed, chemically etched portion, for example.
  • Other processes that are known in the art for forming an object from a monolithic mass may also be used, such as, for example, CNC machining or micro-milling.
  • FIG. IB includes a cross-sectional illustration of the tissue access device 100 formed from the monolithic mass 113 of FIG. 1 A.
  • FIG. IB also includes a schematic diagram illustrating the tissue access device 100 interacting with tissue 135 of a subject.
  • a subject may include any living being, including a human, animal, etc.
  • the tissue 135 of the subject may include brain tissue or any other tissue.
  • the tissue access device 100 may be used while secured in proximity to the subject tissue 135 in an embodiment system.
  • the device 100 may be biocompatible, biostable and sterilizable, it may be implanted within the subject tissue 135 or inserted through the subject skin by virtue of the one or more projections of specific size, shape and pitch.
  • the device 100 may be biocompatible, biostable and sterilizable, it may be implanted within the subject tissue 135 or inserted through the subject skin by virtue of the one or more projections of specific size, shape and pitch.
  • the tissue access device 100 includes a substrate 105 that has a top side 117 and a bottom side 119.
  • the tissue access device 100 further includes one or more projections 120 extending from the bottom side 119 of the substrate.
  • Each of the projections 120 includes an exterior wall portion 127 that defines therein an interior shaft portion 129.
  • the substrate 105 and the multiple projections 120 are formed from the monolithic mass 113 illustrated in FIG.
  • Embodiments with a single projection 120 may be particularly useful for deep brain stimulation (DBS) applications, for example.
  • DBS deep brain stimulation
  • a tissue access device including substrate and single projection 120 may be formed by the
  • the one or more projections may include two or more projections or any other number of multiple projections. Multiple projections may include at least four, at least eight, or at least nine projections, for example. In other embodiments, at least one projection may include one or more lateral exits in the exterior wall portion 127 and one or more lumens 125 in the interior shaft portion 129. As another example, FIG. ID illustrates a 10 x 10 array of projections. In yet other embodiments, devices may include at least 16, at least 32, at least 64, or at least 100 projections, for example.
  • At least one of the one or more projections 120 is functionalized to enable a transfer 133, between the subject tissue 135 and the substrate 105, of at least one of an energy, a signal, a material, and a compound.
  • the one or more projections 120 may be functionalized in this manner for some embodiments.
  • projections 120 may be functionalized to send electrical signals to the tissue or receive (read) electrical signals from the tissue via an electrical conductor.
  • the substrate and projections may be formed from a glass or crystal that is an electrical insulator.
  • the multiple projections 120 may be functionalized via cores inserted and positioned within the respective interior shaft portions of the projections. An example is illustrated hereinafter in connection with FIGS. 3A-3D, in which the respective cores are formed from conductive metal microwires inserted into interior shaft portions of the projections.
  • a fluid precursor material process as illustrated and described in connection with FIGS. 4A-4F.
  • This process may be used to produce a specific tissue access device that is functionalized via glass-like carbon (GLC) electrically conductive cores, for example.
  • GLC cores like the metal microwire cores described in connection with FIGS. 3A-3-D, are useful for delivering electrical energy to, sending electrical signals to, or reading electrical signals from, brain tissue or other subject tissue.
  • GLC cores can be used as well to record electrochemical signals such as the level of neurotransmitter dopamine with ultra-low resolution. Regarding this point, reference may be made to Sci. Rep.
  • GLC electrodes have purely capacitive behavior with exceptionally high charge storage capacity (CSC)
  • projections 120 functionalized with GLC can be used to deliver several billion cycles of electrical pulses at high charge densities to achieve efficient stimulation of different types of tissues.
  • GLC cores are particularly advantageous because they can be much more durable and have much longer usable lifetimes than even noble metal microwire cores, for example.
  • projections 120 may be functionalized to transfer optical or thermal energy to tissue.
  • optical energy may be delivered to the subject tissue if the projections 120 are configured as waveguides.
  • waveguides may be laser written into glass and other materials by changing the refractive index of the material along a desired path.
  • a waveguide may be laser written into one or more of the projections 120, and preferably extending into or through the substrate 105, before or after the monolithic mass 113 is modified to form the substrate 105 and projections 120.
  • the interior shaft portion 129 may be a path of modified refractive index formed by the laser writing.
  • the interior shaft portion 129 can be built to transfer simultaneously electricity and light from/to the subject tissue 135.
  • the projections 120 may be functionalized for delivery of materials or compounds, such as fluids, drugs, etc. to the tissue 135. In other examples, projections 120 may be functionalized for receipt of fluids, materials, tissue samples, etc. from the subject tissue 135.
  • the interior shaft portion 129 may contain one or more lumens 125 connected to different exits along the exterior wall portion 127 in order to transfer 133 materials or compounds at or from different locations of the subject tissue 135.
  • FIG. 1C is a schematic illustration of an embodiment of a neural interface system 10 including an implantable device 100’, which is an embodiment of the tissue access device 100 illustrated in FIG. IB.
  • the system 10 also includes a processing unit (PU) 103.
  • the implantable device 100’ is configured to be implanted in a subject and to access a tissue, of the subject. This access may include recording physiologic parameter information of the subject, such as electrochemical signals of the subject’s brain.
  • System 10 can further include processing unit 103 which can receive information (“data” or“information” herein) from implantable device 100’.
  • processing unit 103 provides energy and/or a material (e.g., a pharmaceutical drug or other agent) to implantable device 100’.
  • a material e.g., a pharmaceutical drug or other agent
  • Processing unit 103 can be implanted in the subject, be external to the subject, or it can include at least one component that is implanted in the subject and at least one component that is external to the subject.
  • Implantable device 100’ and processing unit 103 can be operably connected (e.g., at least electrically connected) via one or more flexible wires or traces positioned within a conduit, such as conduit 60 shown.
  • the system 10 may be fully implanted as part of a miniaturized wireless neural interface system that transfers
  • conduit 60 may be filled with a conductor material and/or a non-conductor material; said material, when filling conduit 60, allows a seal which blocks an entry of additional material, for example tissue materials that could degrade a physiological signal detection by the device.
  • conduit 60 further includes one or more fluid delivery tubes, one or more optical fibers, and/or one or more waveguides.
  • Conduit 60 can include a flexible conduit, and it can include one or more separate conduits.
  • system 10 further includes a connector, connector 101 shown, configured to operably connect implantable device 100’ and processing unit 103.
  • Connector 101 can include one or more electrical connectors, fluid connectors, optical connectors, and/or sound connectors.
  • System 10, implantable device 100’, processing unit 103, conduit 60, and/or connector 101 can include one or more components and/or include a similar construction and arrangement as described in U.S. Provisional Application No. 62/665,486, filed May 1, 2018, entitled “Neural Interface System,” and PCT Application No. PCT/EP2019/061129, filed April 30, 2019, the entire contents of which are hereby incorporated herein by reference for all purposes.
  • Implantable device 100’ can include a substrate, substrate 105’ shown, with one, two, or more projections 120’ extending therefrom.
  • Each projection 120’ includes a shaft portion (also referred to herein as an“interior shaft portion”), shaft 121, with each shaft 121 including a distal portion, distal end 122.
  • One or more shafts 121 can include a lumen, lumen 125, and one or more lumens 125 can surround a core, core 130.
  • Cores 130 can be configured as one or more electrodes that record electrochemical activity and/or deliver electrical energy, and/or one or more cores 130 can be otherwise functionalized to transfer energy, signals, and/or material to and/or from subject tissue proximate device 100’.
  • One or more lumens 125 can be void of (e.g., not surround) a core 130 (e.g., when lumen 125 is configured to transfer material to and/or from subject tissue).
  • one or more shafts 121 can be void of (e.g., not include) a lumen 125 (e.g., one or more shafts 121 extending from substrate 105’ that are simply included to stabilize device 100’ further in tissue or to deliver light to the subject tissue 135).
  • Implantable device 100’ can include one, two, or more materials configured to be resistant to a foreign body response by tissue surrounding implantable device 100’ after implantation. At least a portion of implantable device 100’ (e.g., substrate 105’ and/or projections 120’) can include an insulating inorganic material selected from the group consisting of: glass, such as borosilicate glass, floated borosilicate glass, Borofloat® glass, low-thermal expansion borosilicate glass, Pyrex® glass, and/or soda lime glass; sapphire; fused silica; quartz; lithium-aluminosilicate glass-ceramic; Zerodur® material; alumina; ruby; crystals; polymers and combinations thereof.
  • glass such as borosilicate glass, floated borosilicate glass, Borofloat® glass, low-thermal expansion borosilicate glass, Pyrex® glass, and/or soda lime glass
  • sapphire fused silica; quartz; lithium-aluminosilicate glass
  • substrate 105’ and/or projections 120’ include at least two or more materials of the previous list of materials either mixed or in layers. In some embodiments, substrate 105’ and projections 120’ include at least one similar material. In some embodiments, the all tissue contacting portions or the entirety of implantable device 100’ includes an insulating inorganic material, such as one or more of the materials listed hereinabove.
  • the substrate 105’ and the projections 120’ may be formed from a monolithic mass as described in connection with FIGS. 1 A-1B, and the monolithic mass may include one or more of the materials selected from the group given hereinabove, for example.
  • Implantable device 100’ can be fabricated according to procedure 200 described hereinafter in reference to FIG. 2.
  • the implantable devices 100’ of the disclosure are configured to be manufactured in an automated and reliable manner, and provide flexibility in component features, such as length, shape, and/or configuration of projections 120’ and cores 130.
  • the implantable devices 100’ address the issue of long term biostability of currently available products.
  • Implantable device 100’ can include biostable bulk materials for providing insulation and support, which can be reliably interfaced with optically and/or electrochemically active materials included to functionalize implantable device 100’.
  • Projections 120’ can be configured to be positioned within subject tissue (e.g., brain tissue), such that substrate 105’ can be positioned on or at least proximate a tissue surface, and projections 120’ extend into the tissue.
  • Implantable device 100’ can include at least 1, 2, 4, 8, and/or 9 projections 120’. In some embodiments, implantable device 100’ includes no more than 64, 100’, and/or 1000000 projections 120’.
  • Each projection 120’ includes a length LI extending from substrate 105’ to the distal-most end of each projection 120’. LI can include a length of at least 0.01mm, 0.25mm, 0.50mm, or 0.75mm.
  • LI includes a length of no more than 1.0mm, 1.5mm, 2.0mm, or 300mm.
  • projections 120’ include at least two projections with relatively similar lengths LI.
  • projections 120’ include at least two projections with different lengths LI, such as to allow recording of physiologic parameters from multiple depths within the tissue (e.g., to record electrical activity from cells of interest that are at different depths from the tissue surface onto which implantable device 100’ is positioned) and also to facilitate the device 100’ insertion in subject tissue 135.
  • Each projection 120’ is positioned a separation distance D1 from neighboring (adjacent) projections 120’.
  • D1 can include a distance of at least 0.01mm, 0.10mm, 0.20mm, and/or 0.40mm. D1 can include a distance of no more than 0.8mm, 1.6mm, 4.0mm and/or 300mm. In some embodiments, multiple projections 120’ can be positioned at a relatively similar distance D1 between each other. In some embodiments, multiple projections 120’ can be positioned at different (e.g., relatively dissimilar) distances D1 between each other.
  • all or a subset (e.g., at least two) of projections 120’ include a relatively straight, cylindrical shape as shown.
  • one or more projections 120’ can include other shapes, such as curved shapes, conical shapes, ballistic shapes, mushroom shapes, cylindrical shapes, cylindrical shapes with chamfered tips, cylindrical shapes with conical tips (e.g., including multiple exits).
  • Projections 120’ can include single or multiple longitudinal exits (e.g., slits, holes, and/or other openings) proximate distal end 122, and/or projections 120’ can include single or multiple lateral exits (e.g., slits, holes, and/or other openings) along the elongate shaft 121.
  • Lateral exits are examples of“lateral extensions,” as used herein. Certain example lateral extensions applicable to projections that are functionalized for transfer of electrical signals are described in connection with FIGS. 5A-5C, for example.
  • projections 120’ are arranged in an array pattern, such as a geometric pattern selected from the group consisting of: linear; triangular; square;
  • projections 120’ are arranged in a rectangular grid of projections (e.g., with similar or dissimilar spacing between projections), such as a 2 by 2, 2 by 4, 2 by 6, 4 by 4, 4 by 6, 4 by 8, 5 by 6, 5 by 7, 6 by 6, 6 by 8, 6 by 10,
  • Projections 120’ each include an elongate shaft 121 including a distal portion, distal end 122.
  • all or a subset of projections 120’ include an open (non-sealed) distal end (e.g., an open distal-most portion of distal end 122), as shown in FIG. 1C.
  • one or more projections 120’ can include a closed distal end (e.g., a closed distal-most portion of distal end 122).
  • One or more projections 120’ can include a uniform cross-sectional profile and/or a varied profile.
  • all or a subset of projections 120’ include an elongate shaft 121 with a tapered distal end 122 (e.g., a pointed and/or sharpened distal portion of shaft 121 configured to penetrate tissue, such as brain tissue, relatively atraumatically).
  • one or more projections 120’ include an elongated shaft 121 with a blunt or otherwise rounded distal end 122.
  • the shaft may have a smooth or irregular surface of different geometries (protrusions, ring-like elevations or depressions, or pits).
  • all or a subset of projections 120’ are constructed and arranged as microneedles and/or micropipettes.
  • all or a subset of projections 120’ include a central opening along its length, lumen 125.
  • Each lumen 125 can surround an inserted component, core 130.
  • Each core 130 can include a functionalized active core, such as an electrically, chemically, optically, and/or sonically active core configured to carry a signal and/or energy, to and/or from tissue proximate the distal end 122 of shaft 121.
  • at least a portion of core 130 can be configured as an electrode to record electrochemical activity (e.g., neuronal firing) in tissue, and/or deliver electrical energy to tissue.
  • Each core 130 can be operably connected to conduit 60 (e.g., on the end of conduit 60 opposite distal end 122 of shaft 121) via one or more wires, tubes, optical fibers, waveguides, and/or other functional filaments, filament 65 shown.
  • the top side of substrate 105’ can be covered with an insulator, insulator 70 shown.
  • Insulator 70 can include one or more insulating materials, such as a polymer, ceramic, a silicone, and/or an epoxy resin. Insulator 70 can be positioned above each projection 120’ after all the associated cores 130 are inserted into the projections 120’ and any operable attachments to conduit 60 have been made.
  • Each lumen 125 can be configured to receive or otherwise support an inserted core 130 including one, two or more functional elements and/or materials selected from the group consisting of: glassy carbon (GC, also referred to as“vitreous carbon,”“glass-like carbon,” and the like) or other material configured to record electrochemical signals; noble metals and/or related alloys (e.g., platinum-iridium); conductive threads, such as threads including carbon fibers; microwires; conductive plastics (e.g., PEDOT:PSS, epoxy charged with conductive nanoparticles, noble metal nanoparticles, and/or carbon nanoparticles);
  • GC glassy carbon
  • conductive threads such as threads including carbon fibers
  • microwires e.g., PEDOT:PSS, epoxy charged with conductive nanoparticles, noble metal nanoparticles, and/or carbon nanoparticles
  • hybrid materials e.g., silicone rubber and/or other biopolymers embedded with gold- platinum nanoparticles or conjugated polymers); ceramics; therapeutic agents; carbon powders and/or substances derived therefrom; cured liquids, such as conductive inks and/or polymers; a transducer or other functional element; and combinations of these.
  • projections 120’ include threads disposed within lumens 125, threads 126 shown, such as when an inserted core 130 includes mating threads 131.
  • threads 126 and threads 131 each include conductive threads configured to transfer electrical signals and/or energy between core 130 and projection 120’.
  • threads 126 are fixedly disposed within lumen 125, such that threads 126 cannot move relative to the projection 120’.
  • the threads 126 are not fixedly disposed within lumen 125, such that the threads 126 are adjustable in position or otherwise moveable relative to projection 120’.
  • Core 130 can further include a material configured to surround (e.g., provide structural support) to the threads 126.
  • a portion of core 130 can be configured to support threads 126 at a length measured from the distal end of projection 120’, such as a length at least 0.01mm and/or at most 300mm, such as a length of approximately 0.5mm.
  • projections 120’ include lumen 125 and cores 130 include glassy carbon disposed within lumens 125.
  • the glassy carbon can be formed from a fluid precursor that is configured to be converted into an electrically conductive and biostable material via one or more thermal treatments, such as described hereinafter in reference to FIG. 2 or FIGS. 4A-4F.
  • the glassy carbon can be configured to adhere to an inner surface of projection 120’ (e.g., to adhere to the wall of projection 120’ surrounding lumen 125).
  • the glassy carbon can include electrochemical properties configured to record electrochemical signals emitted by subject tissue (e.g., action potentials and/or other neural signals emitted by brain and/or other neural tissue).
  • the glassy carbon can include a high elastic modulus (e.g., a high Young’s modulus of at least 1 GPa) configured to facilitate the insertion of projection 120’ into subject tissue.
  • projections 120’ are used as a support and/or are consumable in the fabrication process of cores 130 from fluid precursors including glassy carbon and related variants as bulk or electrode material.
  • “Related variants” should be understood to be carbon-based materials (e.g., pyrolytic carbon, graphite, graphene, boron- doped diamond, DLC, CNT).
  • cores 130 including glassy carbon and related variants may form an external surface of projections 120’.
  • the high Young’s modulus of glassy carbon facilitates insertion of projections 120’ into tissue, and the elasticity of glassy carbon enhances the mechanical robustness of the projections 120’.
  • An outer layer can include one or more biocompatible insulating materials (e.g., parylene, multilayer coating of parylene and silica, liquid crystal polymer, atomic layer, or physical vapor deposited nano-engineered coatings and related thin films, silicone, epoxy, SU-8 and combinations thereof).
  • biocompatible insulating materials e.g., parylene, multilayer coating of parylene and silica, liquid crystal polymer, atomic layer, or physical vapor deposited nano-engineered coatings and related thin films, silicone, epoxy, SU-8 and combinations thereof.
  • projections 120’ form a glass structure used as a support and/or a consumable in the formation of glassy carbon electrode shanks. At least a projection or a portion of core 130 is configured to form an electrode. Such an electrode may include one or more glassy carbon electrode shanks.
  • projections 120’ are configured to perform
  • the interior shaft 121 may include a material portion with a modified index of refraction to act as a light waveguide.
  • One or more projections 120’ may be configured to transfer, simultaneously or asynchronously, light and electricity to the subject tissue 135 with high spatial resolution (e.g. few microns apart).
  • implantable device 100’ is configured to treat the subject (e.g., in addition to recording physiologic information of the subject).
  • Projections 120’ can include a lumen 125 that is configured to receive one, two, or more therapeutic agents disposed within and/or otherwise delivered to lumen 125.
  • Projections 120’ can be configured to deliver the therapeutic agent from lumens 125 to subject tissue.
  • projections 120’ are operably connected to a fluid delivery pump (e.g., of processing unit 103) and/or tubing (e.g., of conduit 60) configured to provide the therapeutic agents to projections 120’.
  • implantable device 100 is configured to sample subject tissue (e.g., in addition to recording physiologic information of the subject).
  • Implantable device 100’ can be configured to perform a microdialysis of subject tissue, such that projections 120’ are configured to record (e.g., sample) free, unbound analyte concentrations of subject tissue.
  • Processing unit 103 can be configured to process data, such as data including information (e.g., recorded neural and/or other physiologic signals) received from
  • Data processing performed by processing unit 103 can include but is not limited to: amplifying; referencing; re referencing; mathematically processing; digitizing; multiplexing; condensing; compressing; notch filtering; band-pass filtering; scaling; zero-centering; averaging; determining a maximum; determining a minimum; determining a mean; thresholding; transforming;
  • processing unit 103 includes memory storage circuitry configured to store information, such as information received from implantable device 100’ or another component of system 10, and/or information processed by processing unit 103.
  • processing unit 103 may include an antenna or telemetry link to transmit or receive data wirelessly to another processing unit system.
  • the data processing functionality of the processing unit 103 set forth herein can be implemented in software or in hardware or in a combination of software and hardware.
  • the processing unit 103 may include one or more microprocessors, microcomputers, microcontrollers, digital signal processors, central processing units, state machines, logic circuitries, and/or any device devices that manipulate signals based on operational instructions.
  • the processing unit 103 in some embodiments may be configured to fetch and execute computer- readable instructions stored in associated memory, such as volatile and/or non-volatile, removable and/or non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules, or other data.
  • the functionality of the processing unit 103 could be implemented by special purpose hardware-based computer systems or circuits, etc., or combinations of special purpose hardware and computer instructions.
  • processing unit 103 includes a fluid delivery pump, such as a pump configured to deliver a pharmaceutical or other agent to one or more projections 120’ (e.g., to lumens 125 as described hereinabove).
  • a fluid delivery pump such as a pump configured to deliver a pharmaceutical or other agent to one or more projections 120’ (e.g., to lumens 125 as described hereinabove).
  • processing unit 103 includes a diagnostic portion configured to analyze material (e.g., blood and/or other tissue) sampled via one or more projections 120’ (e.g., in a microdialysis procedure as described hereinabove).
  • material e.g., blood and/or other tissue
  • FIG. 2 is a flow diagram illustrating a procedure 200 for manufacturing an implantable device of a neural interface system, consistent with the disclosure.
  • Procedure 200 is described using neural interface system 10 and its components described hereinabove in reference to FIG. 1C.
  • substrate 105’ and/or projections 120’ are fabricated from one, two, or more insulating inorganic materials, as described hereinabove in reference to FIG. 1C.
  • implantable device 100’ is fabricated through a subtractive 3D printing process (e.g. Femtoprint® process) configured to shape insulating inorganic material into an array of projections, projections 120’.
  • a subtractive 3D printing process e.g. Femtoprint® process
  • projections 120’ obtained by a subtractive 3D printing process are used as a support and/or are consumable at 209 in the fabrication process of cores 130 made, for example, from conversion of fluid precursors to functional materials such as glassy carbon, noble metals, conductive polymers or conductive fluids and related variants.
  • the procedure 200 can be configured to minimize the number of interfaces between different materials that can result in potential points of failure.
  • projections 120’ are functionalized, such that all or a subset of lumens 125 receive a core 130 (e.g., a functional element and/or material as described hereinabove in reference to FIG. 1C).
  • Functionalized projections 120’ can include a hermetic and biostable interface between elongate shaft 121 and the functional element and/or material, where the interface can be configured to prevent or at least reduce ingress of body fluids and moisture.
  • all or a subset of lumens 125 receive a core 130 including a wire and/or paste, such as including one, two or more noble metals/and or related alloys.
  • core 130 includes one, two, or more carbon fibers.
  • core 130 includes one, two, or more carbon powders.
  • core 130 includes one, two, or more carbon derived substances. In some embodiments, core 130 includes one, two, or more cured liquids, such as conductive inks and/or polymers.
  • all or a subset of lumens 125 surround a projection 120’ including cores 130 made from materials such as glassy carbon derived from a fluid precursor.
  • the fluid precursor can be applied to an inner surface of lumen 125, and a centrifugal force or negative pressure can be applied to achieve a uniform distribution of the fluid precursor within each lumen 125.
  • the fluid precursor can then be converted into an electrically conductive and biostable material via one or more material conversion treatments.
  • the material conversion treatment includes a controlled pyrolysis process (e.g., chemically transforming the fluid precursor at elevated temperatures in the absence of oxygen).
  • implantable device 100 (e.g., functionalized projections 120’ including cores 130) is operably connected to processing unit 103.
  • implantable device 100’ can be operably connected to processing unit 103 via connector 101.
  • cores 130 are operably connected to one, two, or more filaments 65 or bumps, such as operably connected via wire bonding, soldering, welding, and/or curing using a conductive organic fluid. Filaments 65 can then be covered with insulator 70, as described hereinabove.
  • projections 120’ can be operably connected to an electronic component (not shown), such as a component configured to amplify recorded signals and/or convert the recorded signals to digital signals (e.g., the electronic component may include an analog-to-digital converter).
  • the electronic component can be connected to filaments 65 and covered with insulator 70.
  • Filaments 65 can be operably connected to processing unit 103. Alternatively, filaments 65 can be operably connected to connector 101 (e.g., via conduit 60). In some embodiments, processing unit 103 and/or connector 101 are operably connected to one, two, or more microfluidic channels (not shown), such as fluid tubes configured to deliver therapeutic agents to projections 120’ as described herein. In some embodiments, processing unit 103 and/or connector 101 are operably (e.g., optically) connected to one, two, or more optical fibers (not shown), such as to provide photostimulation or optogenetic stimulation to subject tissue via projections 120’.
  • implantable device 100 is described in reference to implanting within a subject (e.g., under the skin of the subject), in some embodiments, implantable device 100’ can include a tissue access device that is positioned proximate tissue of the subject, without being implanted in the subject.
  • FIGS. 3A-3D are illustrations of a projection 320 that can form part of an embodiment tissue access devices such as the device 100 in FIG. IB or the device 100’ in FIG. 1C, for example.
  • FIGS. 3A-3D illustrate the projection 320 at various stages of functionalization according to a functionalization process that includes inserting a metal microwire forming a core 339 into the interior shaft portion 129 of the projection 320.
  • the metal microwire is a platinum/iridium (Pt/Ir) wire, but in other embodiments, the metal microwire can be of gold or another noble metal or alloy thereof, for example.
  • Drawing feature 337 symbolizes that the actual length of projection 320 is shortened for better visualization of the device.
  • the projections 320 protrude from the bottom side 119 of the substrate 305. It should be understood that the substrate 305 and projections 320 are not shown at scale, either individually or relative to one another.
  • FIG. 3 A particularly illustrates the projection 320, which includes the inner shaft portion 129 and the exterior wall portion 127, forming a glass capillary made using the Femtoprint® process described hereinabove, which may be understood to be a form of subtractive 3D printing, wherein a substrate and projections therefrom are formed from a monolithic mass.
  • the projection 320 is not yet functionalized for a purpose of receiving electrical signals from, or delivering electrical signals to, a subject tissue.
  • FIG. 3B illustrates the projection 320 at a later time -in the functionalization process, at which the Pt/Ir wire core 339 has been inserted into the interior shaft portion 129.
  • FIG. 3C illustrates the projection 320 at yet a later time than in FIG. 3B, when a distal end 122 of the Pt/Ir wire core 339 has been laser or arc welded to a distal end 122 of the projection 320, as illustrated by the Pt/Ir laser weld 341.
  • the distal end 122 of the projection is opposite a proximal end 123 of the projection 320, where the proximal end 123 is contiguous with the bottom side of the substrate.
  • 3D illustrates the projection 320 at still a later stage of this example functionalization, at which time the Pt/Ir wire core 339 has been laser welded to the proximal end 123 of the projection 320 via a laser weld 343.
  • a bond pad 345 may be created to facilitate the electrical connection to filaments 65 and improve the hermeticity and insulation of projection 320.
  • Naked (unfunctionalized) glass arrays may be produced following the
  • FMF fluid medium functionalization
  • the organic fluid precursor material may be transformed into a conductive solid material core through various thermal treatments in conventional and inert gas atmospheres.
  • the objective of this FMF process is to convert an empty, unfunctionalized glass array in a functionalized implantable sensor capable of reading and writing
  • a fluid precursor constituting a high-quality source of carbon may be used to produce Glass-Like Carbon (GLC) via pyrolysis of the organic polymer in an inert atmosphere.
  • GLC Glass-Like Carbon
  • One example of such a source is a Photoresist (PR) SU-8 GM1040 available from Gersteltec Sari, Switzerland, which has high chemical purity and can be patterned via UV-photolithography. This example source has been used in development of the example process described in relation to FIGS. 4A-4F, but other sources may be used.
  • FIGS. 4A-4D are illustrations of various stages of functionalization of a naked glass array 447 using the example FMF process.
  • FIGS. 4E-4F are illustrations of a centrifugation assembly 450 that can be employed to load fluid PR onto the back of the array 447.
  • the array depicted in FIGS. 4A-4D includes a substrate 405 with projections 420 protruding from the bottom side 119 of the substrate 405. It should be noted that neither the substrate 405 nor the projections 420 are shown to scale, either individually or relative to each other.
  • the GLC functionalization process described below in relation to FIGS. 4A-4F contemplates using an embodiment device produced by the Femtoprint® process, but it can also be applied to embodiments produced by other processes that are known in the art for forming an object from a monolithic mass.
  • functionalized glass capillary projections 420 may be cleaned by immersion in acetone (5’), isopropyl alcohol (IP A) (5’), and deionized (DI) FhO (5’) and heated up on a hotplate at 200°C for 15’.
  • the surface of the array can then be activated by plunging it for 5’ in a plasma consisting of 150 ml/min O2 and 50 ml/min N2.
  • the PR may be loaded only on the back of the array using a custom-made manufactured metal holder 451, O-ring 453, and plastic cap 455 that are illustrated in FIGS. 4E-4F as part of the centrifugation assembly 450.
  • FIG. 4B illustrates the array 447 with the loaded fluid precursor material 439, constituting a loaded array 447’.
  • the loading may be completed by use of a fluid precursor loader 457, as illustrated in FIG. 4E.
  • the assembly 450 may be introduced into the bottom of a Falcon® Tube Diam. 10 mm adapted for centrifugation in a centrifuge.
  • HeraeusTM MultifugeTM 3-SR 2006 model, Economics-Nr.: 75004371.
  • the assembly may be centrifuged using the following parameters: Acceleration level 9, Deceleration level 7, Revolutions per minute 670, time G, temperature 25°C.
  • the assembly may then be thermally activated by placement in an incubator at 70°C for 3.125 hours.
  • the assembly may be taken from the incubator and placed on top a hotplate that ramps up to 190°C at a rate of 10°C/min.
  • the assembly may be left for 30’ at 190°C and then cooled softly at a rate inferior to 10°C/min.
  • the assembly may be centrifuged, then thermally activated, then heated to an elevated temperature, then maintained at the elevated temperature, and then cooled. Specific parameters will depend upon the fluid precursor used and upon configuration of the specific device configuration being prepared.
  • the assembly 450 may then be placed inside an inert atmosphere furnace (e.g., PEO-061 by ATV Technologic GmbH, Germany) and may be further processed by the following example thermal treatment under a constant flux of N2 of at least 1.0 seem: (i) ramp up at rate of 10°C/min from 20°C to 200°C, (ii) stay 30’ at 200°C, (iii) ramp up at rate of 10°C/min from 200°C to 900°C, (iv) stay 60’ at 900°C, (v) ramp down at rate of 10°C/min from 900°C to 20°C.
  • the fluid precursor material 439 is transformed into a GLC core 439’, such that the array is transformed into a functionalized tissue access device 400, as illustrated in FIG. 4C.
  • FIG. 1C Further process steps may also be completed to optimize function of the device 400 and prepare it for use within a neural interface system such as the system 10 illustrated in FIG. 1C.
  • the backside of the functionalized array tissue access device 400 may be cleaned with a cotton rod and IPA for excess of conductive carbon material (i.e. GLC). If the backside of the array does not contain enough GLC in the backside pads, a fluid drop of PR may be added, and previous parts of the process may be repeated, as will be understood, to transform the fluid drop of PR into a GLC drop 449, as illustrated for example in FIG. 4D.
  • GLC conductive carbon material
  • the backside of the array may be connected via conductive epoxy to a biocompatible lead cable (filament 465, as illustrated in FIG. 4D) with pads in the distal end that mirror the disposition of the backside pads of the glass array.
  • a biocompatible lead cable filament 465, as illustrated in FIG. 4D
  • a glob top i.e. an encapsulation that protects fragile wire bonds and connections
  • a biocompatible epoxy approved for long-term implantation e.g., those from EPO- TEK®
  • the other side of the lead cable may be connected to a preferred connector following methods known to those skilled in the art.
  • An example of a functionalized tissue access device 400’ is illustrated in FIG. 4D.
  • GLC has a wider electrochemical window than gold or platinum, and carbon affords higher applied voltages in solution without producing electrolysis of water, so it has up to 35 times longer lifetime compared to noble metal electrodes;
  • GLC has excellent biocompatibility;
  • GLC is chemically inert in almost all solvent/electrolytes,
  • GLC has good mechanical properties, with a hardness of 6 - 7 on Moh’s scale similar to that of quartz and a Young’s Modulus in the range of 10 - 40 GPa that is similar to that of glass;
  • GLC has outstanding MRI compatibility; and
  • GLC can read both chemical and electrical signals from the brain, so it is multi-modal.
  • the multi-modal aspect of GLC is further described in M.
  • FIGS. 5A-5C are perspective-view illustrations of projections 520a-c of various embodiment tissue access devices that are configured to be electrode projections, and which include lateral extensions that constitute electrodes.
  • the projections of FIGS. 5A-5C may form part of any embodiment device described herein, such as the device 100 of FIG. IB or the device 100’ of FIG. 1C.
  • the lateral extensions extend through exterior wall portions 527 of the projections, on or proximate to the distal ends 122 of the projections. Proximal ends 123 of the projections are proximate to the bottom side of a substrate, which is not illustrated in FIGS. 5A-5C.
  • FIG. 5 A particularly illustrates a quadripolar electrode projection 520a that includes four lateral extensions 559a through the external wall portion 527.
  • FIG. 5B illustrates a directional multipolar electrode projection 520b that includes multiple lateral extensions 559b arranged in an array on the external wall 527.
  • FIG. 5C illustrates an eight- lead electrode projection 520c that can provide for eight individual electrode lateral extensions 559c to be individually set for different electrical stimulation levels.
  • Such electrodes can be used for Deep Brain Stimulation (DBS) therapy and may be fabricated from fully MRI-compatible materials such as glass and carbon by fabricating them from a plane parallel to the base of a monolithic wafer substrate, so that a tissue access device 100’ with very long projection(s) of length close to the diameter of the wafer can be produced; further functionalization of the electrode with carbon-based materials such as GLC can be done with the procedure 200 explained herein.
  • High-resolution imaging techniques such as CT and MRI are used intra- or post-operative to evaluate the exact electrode position in brain surgery. However, such imaging techniques are affected by artifacts created by electrode materials that are slightly paramagnetic such as titanium, stainless steel, and platinum.
  • carbon-based electrodes are diamagnetic materials and do not generate magnetic artifacts in CT and MRI scans, which facilitates the exact positioning of carbon-based DBS and related electrodes in brain surgery.
  • the electrodes shown in FIGS. 5A-5C would be more difficult to fabricate in glass and carbon-based materials with a method other than the procedure 200, because good carbon-based electrodes require a high temperature pyrolysis treatment that can be supported by few materials (e.g., quartz and fused silica), which can only be manufactured presently with complex internal structures (e.g. microfluidic channels) by a femtosecond laser writing and chemical etching process such as, for example, the Femtoprint® process.
  • few materials e.g., quartz and fused silica
  • complex internal structures e.g. microfluidic channels
  • FIG. 6 is a flow diagram illustrating a procedure 600 for manufacturing a tissue access device, such as the tissue access device 100 illustrated in FIG. IB.
  • a substrate and multiple projections are formed from a monolithic mass.
  • the substrate includes a top side and a bottom side, and the multiple projections extend from the bottom side of the substrate, each projection comprising an exterior wall portion defining therein an interior shaft portion.
  • the one or more projections are functionalized, thereby enabling transfer, between the subject tissue and the substrate, of at least one of an energy, a signal, a material, and a compound.
  • Other embodiment procedures may include

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Dermatology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Neurology (AREA)
  • Laser Beam Processing (AREA)
  • Electrotherapy Devices (AREA)
  • Surgical Instruments (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un dispositif d'accès à un tissu d'un sujet, et un procédé correspondant de fabrication du dispositif, qui comprend un substrat comportant un côté supérieur et un côté inférieur. Une ou plusieurs saillies s'étendent du côté inférieur, chaque saillie comprenant une partie de paroi extérieure définissant en son sein une partie tige intérieure, le substrat et les multiples saillies étant formés à partir d'une masse monolithique. La ou les saillies sont fonctionnalisées pour permettre un transfert, entre le tissu du sujet et le substrat, d'au moins un élément parmi une énergie, un signal, une substance et un composé. La fonctionnalisation peut consister à souder au laser des microfils métalliques ou à traiter un précurseur de fluide dans la partie tige intérieure pour former un matériau d'électrode fonctionnelle. Certains modes de réalisation peuvent faire l'objet d'une fabrication plus facile, avec une plus grande flexibilité, et peuvent fournir un accès à un tissu plus fiable que les dispositifs existants.
PCT/IB2020/050543 2019-01-23 2020-01-23 Dispositif d'accès à un tissu Ceased WO2020152628A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201962795973P 2019-01-23 2019-01-23
US62/795,973 2019-01-23
US201962817158P 2019-03-12 2019-03-12
US62/817,158 2019-03-12

Publications (2)

Publication Number Publication Date
WO2020152628A2 true WO2020152628A2 (fr) 2020-07-30
WO2020152628A3 WO2020152628A3 (fr) 2020-09-03

Family

ID=69650654

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2020/050543 Ceased WO2020152628A2 (fr) 2019-01-23 2020-01-23 Dispositif d'accès à un tissu

Country Status (1)

Country Link
WO (1) WO2020152628A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12239833B2 (en) 2023-02-24 2025-03-04 Neural Dynamics Technologies Inc. Adaptive closed-loop DBS stimulation control

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6560472B2 (en) * 2001-06-21 2003-05-06 Microhelix, Inc. Multi-channel structurally robust brain probe and method of making the same
TW200744534A (en) * 2006-06-09 2007-12-16 Univ Nat Chiao Tung Microprobe array structure and manufacturing method thereof
US20120186998A1 (en) * 2006-09-25 2012-07-26 Andre Hermans Microelectrode, Microelectrode formation, and methods of utilizing microelectrodes for charaterizing properties of localized environments and substrates
JP2016002194A (ja) * 2014-06-16 2016-01-12 凸版印刷株式会社 中空型マイクロニードルの製造方法及び中空型マイクロニードル

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
M. VOMERO ET AL.: "Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity", SCIENTIFIC REPORTS, vol. 7, no. 1, December 2017 (2017-12-01)
SCI. REP., vol. 8, 2018, pages 6958

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12239833B2 (en) 2023-02-24 2025-03-04 Neural Dynamics Technologies Inc. Adaptive closed-loop DBS stimulation control

Also Published As

Publication number Publication date
WO2020152628A3 (fr) 2020-09-03

Similar Documents

Publication Publication Date Title
CN109171718B (zh) 微针电极阵列装置
McGlynn et al. The future of neuroscience: flexible and wireless implantable neural electronics
Won et al. Recent advances in materials, devices, and systems for neural interfaces
CN103167892B (zh) 基于液晶聚合物的电极-光极神经接口及其制造方法
Jastrzebska‐Perfect et al. Translational neuroelectronics
CN114126705B (zh) 包括透明封装件的有源植入式医疗设备(aimd)
US10493297B2 (en) Neuromodulation transfection system with passive fluid delivery
Yan et al. Ultraflexible and stretchable intrafascicular peripheral nerve recording device with axon‐dimension, cuff‐less microneedle electrode array
Leber et al. Advances in penetrating multichannel microelectrodes based on the utah array platform
JP2010505563A (ja) 基体を有する装置
CN114847957B (zh) 光电集成的一体化微针阵列式脑机接口器件及其制备方法
US20140107446A1 (en) Flexible microelectrode array with integrated stiffening shank, and method of fabrication
WO2019051163A1 (fr) Système et procédé de fabrication et d'implantation de réseaux d'électrodes de haute densité
CN112869747B (zh) 微电极及其制作和使用方法、塞类装置和微电极系统
Erofeev et al. In vivo penetrating microelectrodes for brain electrophysiology
WO2020152628A2 (fr) Dispositif d'accès à un tissu
Liu et al. Fabrication of a multilayer implantable cortical microelectrode probe to improve recording potential
US20250345133A1 (en) Multifunctional ferromagnetic fiber robots
US11944456B2 (en) Ceramic guide, ceramic guide device, and cermic guide module
EP3762088A1 (fr) Implant auditif
WO2005028019A1 (fr) Microsondes resistant a la rupture
US20150094793A1 (en) Fluidic conductors for implantable electronics
Du et al. Advanced Fibers for Optogenetic Modulation
US12318224B2 (en) Wearable biosensor device
CN118892320B (zh) 一种用于监测脑皮层和核团及微量给药的闭环电极

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20706810

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20706810

Country of ref document: EP

Kind code of ref document: A2