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WO2025183831A1 - Actionneur de distributeur de précision - Google Patents

Actionneur de distributeur de précision

Info

Publication number
WO2025183831A1
WO2025183831A1 PCT/US2025/012925 US2025012925W WO2025183831A1 WO 2025183831 A1 WO2025183831 A1 WO 2025183831A1 US 2025012925 W US2025012925 W US 2025012925W WO 2025183831 A1 WO2025183831 A1 WO 2025183831A1
Authority
WO
WIPO (PCT)
Prior art keywords
dispenser
fluid
drop
volume
sensor
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.)
Pending
Application number
PCT/US2025/012925
Other languages
English (en)
Inventor
Benjamin Joseph BECKER
William Hernandez, Jr.
Christopher Steven KOIVISTO
Dawn Lynn NIDA
Michael Otter
Ramon Ricardo SALAZAR
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.)
Ventana Medical Systems Inc
Original Assignee
Ventana Medical Systems Inc
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 Ventana Medical Systems Inc filed Critical Ventana Medical Systems Inc
Publication of WO2025183831A1 publication Critical patent/WO2025183831A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F11/00—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it
    • G01F11/02—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement
    • G01F11/021—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement of the piston type
    • G01F11/023—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement of the piston type with provision for varying the stroke of the piston
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F11/00—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it
    • G01F11/02—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement
    • G01F11/021—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement of the piston type
    • G01F11/029—Apparatus requiring external operation adapted at each repeated and identical operation to measure and separate a predetermined volume of fluid or fluent solid material from a supply or container, without regard to weight, and to deliver it with measuring chambers which expand or contract during measurement of the piston type provided with electric controlling means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1002—Reagent dispensers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/061—Counting droplets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0605—Valves, specific forms thereof check valves
    • B01L2400/0611—Valves, specific forms thereof check valves duck bill valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0605—Valves, specific forms thereof check valves
    • B01L2400/0616—Ball valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0203—Burettes, i.e. for withdrawing and redistributing liquids through different conduits
    • B01L3/0206—Burettes, i.e. for withdrawing and redistributing liquids through different conduits of the plunger pump type
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F22/00—Methods or apparatus for measuring volume of fluids or fluent solid material, not otherwise provided for

Definitions

  • tissue and/or cell samples are commonly placed on slides for analysis.
  • a liquid reagent solution is also typically applied to the slides to facilitate analysis of the sample.
  • the reagent needs to be applied in a precise and consistent manner. However, this can be difficult when performing analysis on a commercial scale. Thus, there is a need for improvement in this field.
  • the system includes one or more dispensers that facilitate multi-dose, fixed volume reagent dispensing with high precision.
  • the system uses a mechanical depression force for dispensing the reagent from the dispensers.
  • the dispensers each have a pump chamber with a built in recharging mechanism that recharges the pump chamber with reagent upon the dispenser being released from actuation.
  • the system uses a micro-stepper motor to depress or otherwise actuate the dispenser in order to dispense a fluid. With the stepper motor, the stroke length of the pumping action used to dispense the fluid can be varied and tightly controlled.
  • the stepper motor can provide a wide range of stroke lengths which in turn allows the system to have the ability to dispense a wide range of fluid volumes.
  • the dispenser system includes a controller and a drop sensor that senses one or more properties of the dispensed drop of fluid such as volume.
  • the drop sensor includes a dual-light curtain through which the drop of dispensed fluid passes. Based on the sensed drop properties, the controller is able to adjust (and calibrate) the stroke length of the pumping action from the stepper motor.
  • the controller commands the stepper motor to reduce the stroke length, and conversely, if the dispensed volume is loo low, the controller instructs the stepper motor to increase the stroke length when actuating the dispenser (for each individual dispenser).
  • This feedback control facilitates precise and accurate reagent dispensing across a wide range of dispensers.
  • the dispenser in some examples has been modified to facilitate a wider range of volumes.
  • the dispenser system utilizes the precise actuation provided by the stepper motor and feedback control to control dispensed volumes.
  • the structures inside the dispenser have been modified to facilitate larger dispense volumes, and in other examples, the structures inside the dispenser have been modified to reduce dispensed volumes, such as from a nominal volume of 95 ⁇ l to 70 ⁇ l. With a larger volume range, the same dispenser is able to dispense a larger variety of fluids and can be used in a larger range of testing protocols.
  • the stroke length limiter has been modified, and the lower intake valve seal or seat was modified to allow a wider volume of fluids to be dispensed.
  • the dispenser system includes a syringe that is used to dispense the fluid to facilitate custom dispense volumes such as is often needed for research applications or titrations.
  • the syringe is supported by a dispenser clip.
  • the dispenser clip includes one or more clip arms that are clipped to the syringe.
  • the syringe is supported by a syringe adapter.
  • the syringe adapter includes an insert, such as a foam insert, that is configured to support the syringe during dispensing.
  • the syringe adapter further includes a carousel adapter that is configured to couple the syringe to a carousel of the dispenser system.
  • Aspect 1 generally concerns a system.
  • Aspect 2 generally concerns the system of any pre vious aspect including a controller.
  • Aspect 3 generally concerns the system of any previous aspect in which the controller includes a processor.
  • Aspect 4 generally concerns the system of any pre vious aspect in which the controller includes memory.
  • Aspect 5 generally concerns the system of any previous aspect including a slide.
  • Aspect 6 generally concerns the system of any previous aspect in which the slide supports a tissue and/or cells to be analyzed .
  • Aspect 7 generally concerns the system of any previous aspect including a fluid.
  • Aspect 8 generally concerns the system of any previous aspect in which the fluid includes a reagent.
  • Aspect 9 generally concerns the system of any previous aspect in which the fluid is configured io stain the tissue on the slide.
  • Aspect 10 generally concerns the system of any previous aspect in which the fluid is a liquid.
  • Aspect 1 1 generally concerns the system of any previous aspect including a dispenser.
  • Aspect 12 generally concerns the system of any previous aspect in which the dispenser is configured to dispense fluid.
  • Aspect 13 generally concerns the system of any previous aspect in which the dispenser is configured to dispense the fluid onto the slide.
  • Aspect 14 generally concerns the system of any previous aspect in which the dispenser includes a reservoir.
  • Aspect 15 generally concerns the system of any previous aspect in which the reservoir is configured to store the fluid .
  • Aspect 16 generally concerns the system of any previous aspect in which the reservoir defines a reservoir chamber.
  • Aspect 17 generally concerns the system of any previous aspect in which the reservoir chamber is configured to store the fluid.
  • Aspect 18 generally concerns the system of any previous aspect in which the reservoir has a cap.
  • Aspect 19 generally concerns the system of any previous aspect in which the cap is configured to be pressed to dispensed the fluid.
  • Aspect 20 generally concerns the system of any previous aspect in which the cap includes a flip cap.
  • Aspect 21 generally concerns the system of any previous aspect in which the dispenser includes a pump.
  • Aspect 22 generally concerns the system of any previous aspect in which the reservoir and the pump are coupled in a reciprocating manner.
  • Aspect 23 generally concerns the system of any previous aspect in which the reservoir and the pump are coupled in a telescoping manner.
  • Aspect 24 generally concerns the system of any previous aspect in which the dispenser includes a spring disposed between the reservoir and the pump.
  • Aspect 25 generally concerns the system of any previous aspect in which the spring is configured to bias the reservoir away from the pump.
  • Aspect 26 generally concerns the system of any previous aspect in which the dispenser includes an inlet valve.
  • Aspect 27 generally concerns the system of any previous aspect in which the inlet valve includes a one-way valve.
  • Aspect 28 generally concerns the system of any previous aspect in which the inlet valve is a cheek valve.
  • Aspect 29 generally concerns the system of any previous aspect in which the inlet valve is a duckbill valve.
  • Aspect 30 generally concerns the system of any previous aspect in which the inlet valve is disposed in the reservoir.
  • Aspect 31 generally concerns the system of any previous aspect in which the inlet valve is configured to seal the reservoir chamber
  • Aspect 32 generally concerns the system of any previous aspect in which the pump defines a pump chamber.
  • Aspect 33 generally concerns the system of any previous aspect in which the pump has a piston.
  • Aspect 34 generally concerns the system of any previous aspect in which the piston is disposed in the pump chamber.
  • Aspect 35 generally concerns the system of any previous aspect in which the piston is configured to pump the fluid.
  • Aspect 36 generally concerns the system of any previous aspect in which the pump has an outlet valve.
  • Aspect 37 generally concerns the system of any previous aspect in which the outlet, valve is disposed along the pump chamber.
  • Aspect 38 generally concerns the system of any previous aspect in which the outlet valve is configured to seal the pump chamber.
  • Aspect 39 generally concerns the system of any previous aspect in which the outlet valve includes a one-way valve.
  • Aspect 40 generally concerns the system of any previous aspect in which the outlet valve is a check valve.
  • Aspect 41 generally concerns the system of any previous aspect in which the outlet valve includes one or more valve members.
  • Aspect 42 generally concerns the system of any previous aspect in which the valve members are ball-shaped.
  • Aspect 43 generally concerns the system of any previous aspect in which the outlet valve includes a valve seat.
  • Aspect 44 generally concerns the system of any previous aspect in which the dispenser includes a nozzle.
  • Aspect 45 generally concerns the system of any previous aspect in which the nozzle is located on the pump.
  • Aspect 46 generally concerns the system of any previous aspect in which the nozzle defines a nozzle opening.
  • Aspect 47 generally concerns the sy stem of any previous aspect in which the nozzle opening is configured to discharge the fluid from the pump.
  • Aspect 48 generally concerns the system of any previous aspect in which the dispenser Includes a stroke limiter.
  • Aspect 49 generally concerns the system of any previous aspect in which the stroke limiter is disposed between the reservoir and the pump.
  • Aspect 50 generally concerns the system of any previous aspect in which the stroke limiter is disposed on the pump.
  • Aspect 51 generally concerns the system of any previous aspect in which the stroke limiter is positioned to contact the reservoir to limit a stroke length of the reservoir when actuated.
  • Aspect 52 generally concerns the system of any previous aspect in which the stroke limiter is shortened to increase a volume of the fluid dispensed.
  • Aspect 53 generally concerns the system of any previous aspect in which the stroke limiter is lengthened to decrease a volume of the fluid dispensed
  • Aspect 54 generally concerns the system of any previous aspect in which the val ve seat of the outlet valve is raised to increase volume of the fluid drawn back from the nozzle.
  • Aspect 55 generally concerns the system of any previous aspect in which the valve seat has a length that corresponds to a volume of the fluid between the outlet valve and the nozzle opening to delay sealing of the outlet valve.
  • Aspect 56 generally concerns the system of any previous aspect in which the delay allows the volume of the fluid between the outlet valve and the nozzle opening to be drawn back into the outlet valve during a return stroke of the pump.
  • Aspect 57 generally concerns the sy stem of any previous aspect in which the length of the valve seat correlates to the length of the stroke limiter to facilitate comparable fluid dispense volumes.
  • Aspect 58 generally concerns the system of any previous aspect in which the pump includes a discharge seal.
  • Aspect 59 generally concerns the system of any previous aspect in which the discharge seal is disposed between the valve seat and the piston.
  • Aspect 60 generally concerns the system of any previous aspect in which the discharge seal is lengthened to reduce a volume of the fluid dispensed.
  • Aspect 61 generally concerns the system of any previous aspect in which the pump includes a spacer disposed inside the discharge seal.
  • Aspect 62 generally concerns the system of any previous aspect in which the spacer rests against the valve seat.
  • Aspect 63 generally concerns the system of any previous aspect in which the spacer is configured to reduce the volume of the fluid dispensed.
  • Aspect 64 generally concerns the system of any previous aspect including a sensor.
  • Aspect 65 generally concerns the system of any previous aspect in which the sensor is configured to sense a drop of the fluid dispensed from the dispenser.
  • Aspect 66 generally concerns the system of any previous aspect in which the sensor is positioned proximal to the nozzle opening where the drop is able to drop through the sensor and onto the slide.
  • Aspect 67 generally concerns the system of any previous aspect in which the sensor is a dual light curtain sensor.
  • Aspect 68 generally concerns the system of any previous aspect in which the sensor is configured to measure a property of the drop of the fluid .
  • Aspect 69 generally concerns the system of any previous aspect in which the sensor is configured to measure volume of the drop.
  • Aspect 70 generally concerns the system of any previous aspect in which the sensor is configured to measure velocity of the drop.
  • Aspect 71 generally concerns the system of any previous aspect in which the sensor is configured to measure acceleration of the drop.
  • Aspect 72 generally concerns the system of any previous aspect in which the sensor includes an emitter.
  • Aspect 73 generally concerns the system of any previous aspect in which the sensor includes a receiver.
  • Aspect 74 generally concerns the system of any previous aspect in which the emitter and the receiver are positioned in an opposing manner in which the drop falls between the emitter and the receiver.
  • Aspect 75 generally concerns the system of any previous aspect in which the sensor includes an entrance light curtain.
  • Aspect 76 generally concerns the system of any previous aspect in which the sensor includes an exit light curtain.
  • Aspect 77 generally concerns the system of any previous aspect in which the emitters and the receivers of the entrance light curtain and the exit light curtain are arranged in an opposite manner to minimize cross talk.
  • Aspect 78 generally concerns the system of any previous aspect in which the sensor is operatively coupled to the controller.
  • Aspect 79 generally concerns the system of any previous aspect including an actuator.
  • Aspect 80 generally concerns the system of any previous aspect in which the actuator is communicatively coupled to the controller.
  • Aspect 81 generally concerns the system of any previous aspect in which the actuator includes a motor.
  • Aspect 82 generally concerns the system of any previous aspect in which the actuator includes an arm.
  • Aspect 83 generally concerns the system of any previous aspect in which the arm is configured to actuate the dispenser.
  • Aspect 84 generally concerns the system of any previous aspect in which the actuator includes a stepper motor.
  • Aspect 85 generally concerns the sy stem of any previous aspect in which the arm is coupled to the stepper motor.
  • Aspect 86 generally concerns the system of any previous aspect in which the actuator is configured to actuate the dispenser to dispense the fluid.
  • Aspect 87 generally concerns the system of any previous aspect in which the actuator is configured to actuate the dispenser at different stroke lengths.
  • Aspect 88 generally concerns the system of any previous aspect in which the stepper motor is configured to actuate the dispenser with multiple different stroke lengths.
  • Aspect 89 generally concerns the system of any previous aspect in which the controller is configured to adjust operation of the actuator based on the property of the drop sensed by the sensor.
  • Aspect 90 generally concerns the system of any previous aspect in which the controller is configured to adjust stroke length of the actuator depending on the volume of the drop sensed by the sensor.
  • Aspect 91 generally concerns the system of any previous aspect in which the controller is configured to shorten the stroke length of the actuator when the volume of the drop sensed by the sensor is too large.
  • Aspect 92 generally concerns the system of any previous aspect in which the controller is configured to lengthen the stroke length of the actuator when the volume of the drop sensed by the sensor is too small.
  • Aspect 93 generally concerns the system of any previous aspect in which the dispenser includes a syringe.
  • Aspect 94 generally concerns the system of any previous aspect in which the dispenser includes a dispenser clip clipped to the syringe.
  • Aspect 95 generally concerns the system of any previous aspect in which the dispenser clip includes a clip body and one or more clip arms extending from the clip body to clip to the syringe.
  • Aspect 96 generally concerns the system of any previous aspect in which the dispenser includes a syringe adapter supporting the syringe.
  • Aspect 97 generally concerns the system of any previous aspect in which the syringe adapter includes an insert defining a syringe opening where the syringe is received.
  • Aspect 98 generally concerns the system of any previous aspect in which the insert is made of foam.
  • Aspect 99 generally concerns the system of any previous aspect including a carousel
  • Aspect 100 generally concerns the system of any previous aspect in which the dispenser includes a carousel adapter.
  • Aspect 101 generally concerns the system of any previous aspect in which the insert is disposed inside the carousel adapter.
  • Aspect 102 generally concerns the system of any previous aspect in which the carousel adapter is configured to couple to the carousel.
  • Aspect 103 generally concerns the system of any previous aspect in which the carousel adapter includes a clip arm configured to clip to the carousel.
  • a spect 104 generally concerns the system of any previous aspect in which the carousel adapter includes a retention tab configured to retain the carousel adapter one the carousel.
  • Aspect 105 generally concerns a method.
  • Aspect 106 generally concerns the method of any previous aspect including dispensing a first drop by actuating a dispenser to a first stroke length with an actuator.
  • Aspect 107 generally concerns the method of any previous aspect including sensing a first property of the first drop wi th a sensor.
  • Aspect 108 generally concerns the method of any previous aspect including determining a correction factor based on the first property with a controller.
  • Aspect 109 generally concerns the method of any previous aspect including determining a second stroke length with the controller based on the correction factor.
  • Aspect 1 10 generally concerns the method of any previous aspect including dispensing a second drop by actuating the dispenser to the second stroke length with the actuator.
  • Aspect 111 generally concerns the method of any previous aspect in which the first s troke length and the second stroke length are different.
  • Aspect 1 12 generally concerns the method of any previous aspect in which the first property of the first drop is volume of the first drop.
  • Aspect 113 generally concerns the method of any previous aspect including finding the volume is above a limit with the controller.
  • Aspect 114 generally concerns the method of any previous aspect including making the second stroke length shorter than the first stroke length in response to the finding the volume is above the limit.
  • Aspect 115 generally concerns the method of any previous aspect inchiding finding the volume is below a limit with the controller.
  • Aspect 116 generally concerns the method of any previous aspect including making the second stroke length longer than the first stroke length in response to the finding the volume is below the limit.
  • FIG. 1 is a block diagram of a dispenser system with an actuator according to one example.
  • FIG. 2 is an enlarged view of the system of FIG. 1 .
  • FIG. 3 is a partial cross-sectional view of one example of a dispenser that can be used in the system of FIG. 1 to dispense smaller dispense volumes,
  • FIG. 4 is a perspective view of a drop sensor used in the system of FIG. 1 .
  • FIG. 5 is a graph showing sources of where traditional dispensers lose fluid.
  • FIG. 6 is a graph showing results from an experiment demonstrating tight control using multiple reagent types.
  • FIG. 7 is a graph illustrating varying amounts of dispensed fluids from an experiment using a stepper motor control technique described herein.
  • FIG. 8 is a graph illustrating the results from another experiment using a stepper motor control method described herein.
  • FIG. 9 is a graph illustrating the results from a further experiment in which stroke extension properties of an actuator were varied.
  • FIG. 10 is a top view of slides resulting from a few staining tests.
  • FIG. 11 is an enlarged cross-sectional view of the dispenser of FIG. 1.
  • FIG. 12 is a side view of a dispenser that can be used in the FIG. 1 system.
  • FIG. 13 is a cross-sectiona l view of the dispenser of FIG. 12.
  • FIG. 14 is an enlarged cross-sectional view of the pump chamber in the dispenser of FIG. 12.
  • FIG. 15 is a perspective view of a stroke l imiter used in the dispenser of FIG. 12.
  • FIG. 16 is a top view of the stroke limiter shown in FIG. 15.
  • FIG. 17 is a cross-sectional view of the stroke limiter as taken along line 17-17 in FIG. 16.
  • FIG. 18 is an enlarged cross-sectional view of the dispenser of FIG. 12 showing the stroke length of the dispenser.
  • FIG. 19 is an enlarged cross-sectional view of a pump chamber in the dispenser of FIG. 12.
  • FIG. 20 is a top view of a spacer used in the dispenser of FIG. 12.
  • FIG. 21 is a side view of the spacer of FIG. 20.
  • FIG. 22 is a cross-sectional side-by-side comparison view of the chamber height in the dispenser of FIG . 1 and the pump chamber in the dispenser of FIG. 12.
  • FIG. 23 is a side view of one example of a syringe dispenser system that can be used in the system of FIG. 1 .
  • FIG. 24 is a perspective view of another example of a syringe dispenser system that can be used in the system of FIG. 1.
  • FIG. 1 illustrates a dispenser system 100 according to one example.
  • the system 100 includes an actuator 105, a dispenser 110 coupled to the actuator 105, a drop sensor 115, and a controller 120 operatively coupled to the actuator 105 and the drop sensor 1 15.
  • the actuator 105 is configured to actuate the dispenser 1 10 so as to dispense reagent in the form of a liquid drop 122 onto a slide 125.
  • the drop sensor 115 is configured to sense the drop 122 as the drop 122 is dispensed onto the slide 125. While the system 100 will be described as dispensing a liquid reagent, the system 100 is configured to displace other types of fluids such as in liquid and/or gaseous form.
  • the dispenser system 100 is designed and constructed to allow precise and finite control of the depression (e.g., stroke length, speed, and/or delay) of the dispenser 110.
  • the actuator 105 includes a motor 130 and an arm 135 that is actuated by the motor 130.
  • the motor 130 is a stepper motor 137.
  • the stepper motor 137 allows the precise control of actuation of the arm 135. In some examples, the stepper motor 137 controls actuation of the arm 135 without the need for extra sensors. As should be recognized, the stepper motor 137 is configured as an electric linear actuator, translating internal discrete angular steps into an external linear motion. A series of electrical pulses in some cases can be applied to the stepper motor 137 to control the angular/linear movement and/or torque applied by the stepper motor 137.
  • the stepper motor 137 incorporates a microcontroller or stepper motor controller that activates coils in a stator of the stepper motor 137 in the proper order to rotate the rotor and actuate in a linear manner at the desired speed and/or torque as well as to the proper position.
  • the controller 120 indirectly controls the stepper motor 137 through the stepper motor controller, but in other examples, the controller 120 directly controls (i.e., without the stepper motor controller) the stepper motor 137 by applying the electrical power directly to the coils of the stator.
  • sensors can be used by the ac tuator 105 and/or controller 120 to monitor stroke length, location, velocity, acceleration, timing, and/or other properties of the arm 135 during operation.
  • the motor 130 in one example can include a resolver that measures the angular (or linear) location, velocity, and/or speed of a rotor and 'or linear position of the actuation axis of the motor 130.
  • the actuator 105 is a Zaber NA motorized linear actuator (e.g., Part Number NA11B30-T4A), but other types of actuators can be used.
  • the aim 135 is coupled to the motor 130 so as to extend and retract from the motor 130 with a linear type motion.
  • the motor 130 and arm 135 of the actuator 105 can be mechanically coupled to one another in other manners.
  • a linkage type arrangement can be used.
  • the arm 135 is coupled to the motor 130 through a crankshaft.
  • one or more gears in a gear train are coupled the motor 130 to the arm 135. The gear train can be used to enhance the control of the stroke length of the arm 135 so as to provide finer control.
  • the gearing can further be used to adjust the applied torque from the motor 130 such that the force applied by the arm 135 to the dispenser 110 can be reduced or increased.
  • the gearing can also be used to adjust the actuation speed.
  • a gear train connects the motor 130 to the stepper motor 137.
  • the motor 130 and arm 135 are directly connected together without any intervening mechanical devices or structures,
  • the position, timing, velocity, and acceleration of the arm 135 can be tightly controlled which turn facilitates tight and consistent control of the volume of the reagent drop 122 dispensed by the dispenser 110. It was found that partial stroke actuation needs fine tuning of the micro-actuation steps via the stepper motor 137, speed modulation/ramps, and delays at the bottom of the stroke to effect reproducible fluid motion needed for drop dispenses. It was uncovered that there is limited fluid acceleration possible due to motor speed limits during the discharge and the area of the opening of the nozzle of the dispenser 110.
  • the dispense volume from the dispenser 110 can be achieved by precisely controlling stroke length of piston movement by replacing pneumatic hammer actuation with discrete motor steps of the stepper motor 137 for depression.
  • the stepper motor 137 allows for greater positioning accuracy and partial strokes.
  • the drop sensor 115 is in the form of a dual light curtain type sensor that senses volume of the drop 122.
  • the drop sensor 1 15 includes a first or entrance light curtain 140 and a second or exit light curtain 142.
  • the entrance light curtain 140 is positioned proximal to the dispenser 1 10
  • the exit light curtain 142 is positioned proximal to the slide 125.
  • the entrance light curtain 140 and the exit light curtain 142 each include an emitter 145 and a receiver 150 that are positioned in an opposing manner so that the drop 122 the reagent drop 122 drops between the emitter 145 and the receiver 150 for both the entrance light curtain 140 and exit light curtain 142.
  • the emitters 145 and receivers 150 for the entrance light, curtain 140 and the exit light curtain 142 are arranged in an alternating manner (i.e., on opposite sides) so as to avoid crosstalk interference.
  • Both the entrance light curtain 140 and the exit light curtain 142 of the drop sensor 1 15 are communicatively or operatively coupled to the controller 120 such as via a wired and/or wireless type connection.
  • the controller 120 shown in FIG. 1 includes a processor .155 and memory 160 operatively coupled io the processor 155.
  • the controller 120 In FIG. 1 illustrates a simplified, form of the controller 120 for the sake of clarity. It should be recognized that the controller 120 in operation includes other components such as input-output devices, a communication bus, and/or a network interface.
  • the controller 120 is operatively coupled to the actuator 105 and the drop sensor 115.
  • the controller 120 is able to precisely control the volume of the reagent drop 122 applied to the slide 125 by setting and controlling the stroke length, timing, and speed of the arm 135 via the stepper motor 137.
  • the controller 120 is able to use feedback control to control the volume of the reagent drop 122 applied io the slide 125 and/or take other corrective actions. For instance, if the processor 155 in the controller 120 finds a trend that volumes of the recently dispensed drops 122 sensed by the drop sensor 1 15 are trending towards a lower range than what would be expected, the controller 120 instructs the stepper motor 137 to lengthen the stroke length of the stepper motor 137 when dispensing the next reagent drop 122 from the dispenser 110. Conversely, if the controller 120 senses that the drop volumes are too large, the processor 155 of the controller 120 can instruct the stepper motor 137 to shorten the stroke length of the arm 135.
  • the controller 120 in some variations can issue an alert or alarm when the drop volume exceeds predetermined or dynamically determined control limits, in most practical use cases, the detection of the drop only happens after the completion of the actuation motion. Any correction then occurs during subsequent dispensing activities.
  • the drop sensor 115 can monitor the initial performance of the dispenser 110 during priming of the dispenser 1 10. The controller 120 via the processor 155 determines one or more correction settings for the dispenser 110, and the resulting correction settings along with an individual identifier (or ID) of the dispenser 110 are then stored in the memory' 160 of the controller 120. In subsequent dispenses used for staining reactions, the correction settings for the individual dispenser 110 are then applied during actuation by the actuator 105. Subsequently, the drop sensor 115 continues to monitor the dispensing process and checks for errors.
  • the dispenser 110 includes a reservoir 205 configured to store a fluid 207 to be dispensed, such as a liquid reagent, and a pump 210 configured to pump or dispense the fluid 207, such as in the form of the drop 122, from a nozzle 215.
  • the reservoir 205 is configured to reciprocate in a telescoping manner relative to the pump 210 in order to pump the fluid drop 122 from the nozzle 215.
  • the reservoir 205 and pump 210 are made of plastic, but the reservoir 205 and/or the pump 210 can be made from different materials like glass and metal.
  • the reservoir 205 has a cap 220.
  • the cap 220 has a flip cap 225 to facilitate refilling of fee reservoir 205, but in other examples, the cap 220 lacks the flip cap 225.
  • the actuator 105 via the arm 135 engages the cap 220 to depress the reservoir 205 relative to the pump 210 so as to facilitate pumping the fluid 207.
  • the dispenser 110 in the depicted example is loaded onto a carousel 230 that facilitates dispensing different fluids 207 via different dispensers 110.
  • the carousel 230 defines a dispenser cavity 235 in which the dispenser 110 is received.
  • the carousel 230 along the dispenser cavity 235 defines one or more clip notches 240 configured to secure the dispenser 110 to the carousel 230. .As shown in FIG.
  • the dispenser 1 10 is dipped into a clip slot 245 defined in a radially outer wall 247 of the carousel 230 via a clip arm 250 of the dispenser 1 10.
  • the clip arm 250 is configured to releasably secure the dispenser 110 to the carousel 230.
  • a user can depress the clip arm 250 so as to unclip or release the dispenser 110 from the carousel 230.
  • the carousel 230 defines a retention slot 255 in which a retention tab of the dispenser 110 is received to secure the dispenser 110 to the carousel 230.
  • the dispensed volume in previous systems was entirely defined by the allowed internal stroke length of the piston in the dispenser.
  • the dispensed volume depended on the tolerances of the plastic parts for the pump chamber and piston in the dispenser.
  • the precise control provided by the stepper motor 137 facilitates finite or discrete control of the depression of the dispenser 110 during dispensing of the reagent.
  • the stepper motor 137 allows for fine control of the stroke length, speed, and delay when dispensing the reagent.
  • the dispenser 110 in one form is modified to allow a wider range of dispensing actions such as wider reagent volume dispensing ranges and types of reagents that can be dispensed with the same type of dispenser 110.
  • the reservoir 205 defines a reservoir chamber 305 in which the fluid 207 is stored.
  • the pump 210 has a pump body 307 that defines a pump chamber 310.
  • the pump chamber 310 is fluidly coupled to the reservoir chamber 305 so as to receive fluid 207 from the reservoir chamber 305.
  • the reservoir 205 has an inlet valve 312 that selectively seals the reservoir chamber 305, Along the fluid path between reservoir chamber 305 and the pump chamber 310, the inlet valve 312 selectively seats the reservoir chamber 305 by acting as a check valve.
  • the inlet valve 312 in one example is a duckbill type valve, but other types of one-way fluid valves can be used on other examples.
  • the pump 210 has a piston 315 with a bead 317 that facilitates pumping of the fluid 207.
  • the piston 315 has one or more flow holes that facilitate flow of the fluid 207 around the piston 315, but in other versions, the piston 315 lacks the flow holes.
  • the pump 210 further hits an outlet valve 320 that acts as a one-way valve to selectively seal the pump chamber 310.
  • the outlet valve 320 is a ball-type check valve, but other types of one-way valves can be used in other examples.
  • the reservoir chamber 305 and the outlet valve 320 are disposed at. opposite ends along the fluid path.
  • the piston 315 is disposed between the inlet valve 312 and the outlet valve 320.
  • the pump 210 has a nozzle opening 325 from which the fluid 207 is dispensed in the form of one or more drops 122 (FIG. 1 ).
  • part of the reservoir 205 is received inside the pump 210 such that the reservoir 205 is able to move relative to the pump 210 in a reciprocating or telescoping manner.
  • the dispenser 110 has a return spring 330 disposed between the reservoir 205 and the pump 210.
  • the return spring 330 is biased to push or extend the reservoir 205 away from the pump 210.
  • the arm 135 of the stepper motor 137 pushes the reservoir 205 towards the pump 210 which in turn compresses the return spring 330.
  • the return spring 330 pushes the reservoir 205 away from the pump 210 to an extended state.
  • the pump 210 has at least one stroke limiter 335 positioned to stop or limit the travel of the reservoir 205.
  • the stroke limiter 335 limits the maximum amount of fluid 207 that can be dispensed in a single stroke. Since the stepper motor 137 is able to accurately control the stroke length or position of the reservoir 205 when depressed, the actuator 105 is able to accurately control the volume of the fluid 207 dispensed over a wide range of volumes.
  • the stroke limiter 335 is shortened as compared to traditional dispensers. This allows the dispenser 110 to have a larger maximum dispensed volume. Consequently, the same dispenser 1 10 in this design is able to be used for a wider range of dispensed volumes and use cases.
  • the nozzle opening 325 is sized to permit a maximum dispensed volume during a single dispensing stroke to be 70 ⁇ l, but in other examples, the nozzle opening 325 is sized differently to pennit different maximum dispensed volumes. Since the stepper motor 137 is able to accurately control the stroke length of the arm 135, the dispenser 110 in other variations does not include the stroke limiter 335.
  • the stroke limiter 335 is further configured to retain a seal 337 that is configured to seal with the piston 315.
  • the outlet valve 320 includes one or more valve members 340 and a val ve seat 345 against which at least one of the valve members 340 seal when the outlet valve 320 closes. Between the piston 315 and the valve seat 345, the outlet valve 320 has a discharge seal 350 with an opening through which the fluid 207 flows. In the depicted example, the discharge seal 350 is raised from the valve seat 345. The discharge seal 350 is configured to seal against the head 317 when the piston 315 is at the full dispensing stroke position. To reduce accidental dripping of the fluid 207 from the nozzle 215, the dispenser 1 10 includes a suck-back feature in which all or most of the fluid 207 located in the nozzle
  • valve seat 345 is sized larger to accommodate the larger maximum volume of the fluid 207 that can be sucked back from the nozzle 215 during the retraction stroke of the reservoir 205, With the valve seat 345 being larger or longer by being positioned farther away from the nozzle opening 325, the valve members 340 have a larger travel distance in order to seal against the valve seat 345. This larger travel distance of the valve members 340 delays closure of the outlet valve 320 which in turn provides greater time for more of the fluid 207 in the nozzle 215 to be drawn into the part of the pump chamber 310 located between the piston 315 and outlet valve 320.
  • the actuator 105 via the arm 135 presses against the cap 220 of the reservoir 205 which in turn causes the reservoir 205 to move or extend towards the pump 210.
  • the inlet valve 312 is closed. With the inlet valve 312 closed, the motion of the reservoir 205 pressurizes the fluid 207 in the pump chamber 310, and the outlet valve 320 is open so as to allow the fluid 207 to flow through the outlet valve 320.
  • the outlet valve 320 is in an opened position, the pressure of the fluid 207 causes the valve members 340 to move away from the valve seat 345 such that the valve members 340 are unseated from the valve seat 345. The fluid 207 is then able to flow through the outlet valve 320.
  • the pressurized fluid 207 from the pump chamber 310 flows out of the nozzle opening 325 to form the drop 122 which is dispensed onto the slide 125 such as is depicted in FIG. 1 .
  • the return spring 330 is compressed.
  • the controller 120 stops the extension stroke of the arm 135 of the actuator 105.
  • the actuator 105 may dwell for a period of time at the fully extended position, but in other cases, the controller 120 may immediately start retracting the arm 135 of the actuator 105.
  • the arm 135 in some examples is retracted quickly such that the 135 no longer contacts the cap 220 of the reservoir 205 as the return spring 330 pushes the reservoir 205 away from the pump 210. In other cases, the arm 135 is retracted at a slower velocity where the arm 135 remains in contact with the cap 220 during the retraction stroke so as io control the velocity at which the reservoir 205 retracts.
  • the piston 315 likewise retracts in the pump chamber 310 so as to reduce the pressure inside the pump chamber 310 which in turn draws the fluid 207 in the nozzle 215 back into the pump chamber 310 through the outlet valve 320.
  • the flow of the fluid 207 through the outlet valve 320 generally draws the valve members 340 towards the end of the valve seat 345 where the valve members 340 seal with the valve seat 345.
  • the valve members 340 do not immediately seal or seat with the valve seat 345 due to the recessed or lengthened nature of the valve seat 345.
  • the length of the valve seat 345 at which the valve members 340 move back towards the valve seat 345 generally correla tes to the volume of the fluid 207 between the outlet valve 320 and the nozzle opening 325.
  • this volume of the fluid 207 between the outlet valve 320 and the nozzle opening 325 is the same or similar to the maximum volume that the dispenser 110 is able to dispense due to the stroke limiter 335, but this volume of the fluid 207 between the outlet valve 320 and the nozzle opening 325 can be different from this maximum dispensing volume set by the stroke limiter 335,
  • the valve members 340 eventually seat or seal with the valve seat 345 such that the fluid 207 in the nozzle 215 is no longer sucked back into the pump chamber 310 past the outlet valve 320.
  • the outlet valve 320 With the outlet valve 320 being closed, the retraction of the reservoir 205 lowers the pressure inside the pump chamber 310.
  • the inlet valve 312 opens to allow the fluid 207 in the reservoir chamber 305 of the reservoir 205 to be drawn into the pump chamber 310 of the pump 210. This action replenishes the fluid 207 inside the pump chamber 310 of the pump 210.
  • FIG. 4 shows perspective views of the drop sensor 115 from both sides.
  • the drop sensor 115 uses dual sensor light curtain technology that facilitates discrimination on multiple reagent types.
  • the drop sensor 115 includes the entrance light curtain 140 and the exit light curtain 142.
  • the entrance light curtain 140 and the exit, light curtain 142 each include the emitter 145 and the receiver 150 that are positioned in an opposing manner so that the drop 122 of the fluid 207 drops between the emitter 145 and the recei ver 150 for both the entrance light curtain 140 and the exit light curtain 142.
  • the emitters 145 and receivers 150 for the entrance light curtain 140 and the exit light curtain 142 are arranged in an alternating manner (i.e., on opposite sides) so as to avoid crosstalk interference.
  • the controller 120 via the drop sensor 1 15 is able io sense the liming, velocity, acceleration, and/or volume of the drop 122.
  • the precision actuator 105 allows finite control of the depression (stroke length, speed, and delay) of the reservoir 205 in the dispenser 110.
  • the entrance light curtain 140 and exit light curtain 142 facilitate surveillance of the drop 122 and feedback for calibrating the system 100 such that consistent drops 122 are dispensed.
  • the stepper motor 137 facilitates partial stroke actuation of the dispenser 110. With the stepper motor 137 used in conjunction with the feedback from the drop sensor 115, the controller 120 is able to fine tune the actuation of the dispenser 110 via the stepper motor 137, the speed modulation/ ramps, and delays at the bottom of the stroke to effect reproducible fluid dispensing motions needed for drop dispensing.
  • the system 100 uses a unique calibration method during automated priming in which the calibration occurs directly on the system 100.
  • the controller 120 via the drop sensor 1 15 is able to measure the actual dispensed drop 122 of fluid 207.
  • the controller 120 uses this feedback signal from the drop sensor 1 15 to establish a correction factor.
  • the drop sensor 1 15 monitors the initial performance of the dispenser 110 during priming of the dispenser 1 10.
  • the controller 120 via the processor 155 determines one or more correction settings for the dispenser 110, and the resulting correction settings along with an individual identifier (or ID) of the dispenser 110 are then stored in the memory 160 of the controller 120.
  • the correction settings for the individual dispenser 110 are then applied during actuation by the actuator 105.
  • the controller 120 may apply the corrective factor to adjust the dispensed volume during normal operation, such as during staining.
  • the controller 120 via the stepper motor 137 may lengthen the stroke length of the arm 135 so as to increase the dispensed volume of the fluid 207.
  • the controller 120 can reduce the stroke length of the arm 135 via the stepper motor 137 such that the volume of the drop 122 is reduced.
  • FIG. 5 shows a graph 500 of sources where traditional dispenser systems waste fluid.
  • the fluids in traditional dispenser systems waste large amounts of fluid through losses such as from a large amount of excess volume used for primes, losses from dispenser variations, overfills from manufacturing losses, and evaporative losses.
  • the system 100 of FIG. 1 is able to control, and in some cases, reduce these fluid volume loss or waste sources.
  • FIG. 6 shows a graph 600 from one experiment in which the system 100 is able to generally demonstrate a less than 5 ⁇ l ( ⁇ 5 ⁇ l) discrimination for multiple reagent types.
  • some assay constructs and processes e.g., probes, user titration, and air knife controlled lower volume puddle
  • dispensers that are not modified in the manner as discussed above with respect to FIG. 3 may benefit from using the actuation and feedback system 100 of FIG. 1.
  • FIG. 7 shows a graph 700 illustrating the results from an experiment using the motion control technique described herein.
  • n 30
  • a reasonable drop dispense variation was achieved in which the sample standard deviation was less than 3 pl (i.e., sd ⁇ 3 ⁇ l).
  • FIG. 8 shows a graph 800 illustrating the results from another experiment using a variable speed and motion control method described herein.
  • a wider range of deliverable volumes were achieved with careful selection of various speed and ramp settings.
  • reliable drop formation was not. achieved.
  • FIG. 9 shows a graph 900 illustrating the results from a further experiment in which stroke extension properties of the stepper motor 137 were varied.
  • stroke extension properties of the stepper motor 137 were varied.
  • velocity and acceleration settings of the stepper motor 137 were changed.
  • the acceleration/ deceleration ramps were varied at the maximum dispensing speed for the stepper motor 137.
  • this graph 900 it appears that there might be some limited ability to dial in the volumes during formation of the drops 122.
  • FIG. 10 shows slides 1000 resulting from a few staining tests. With these tests, it was found that the particular combination of an air knife controlled residual puddle volume after rinses to 200 ⁇ l allows the application of approximately 70 ⁇ l of rare reagent at the same nominal antibody concentration.
  • the staining results shown on the slides 1000 of FIG. 10 where for BCL2 and Ki67 with a mechanically modified dispenser limited to 70 ⁇ l rare reagent dispensed with air knife controlled residual volume of 200 ⁇ l.
  • the staining results were compared to a standard application of 100 ⁇ l rare reagent with 270 ⁇ l nominal residual volume.
  • the volume of the fluid 207 that can be dispensed from the dispenser 110 can be adjusted in a number of manners.
  • the reservoir 205 in the dispenser 110 has a stop ridge 1105 that is configured to contact a stroke limit edge 1 1 10 on the stroke limiter 335.
  • the stop ridge 1 105 and the stroke limit edge 1110 limit the extent to which the reservoir 205 is able to reciprocate relative to the pump 210 so as to control a stroke length 1115 of the pump 210.
  • Controlling the stroke length 1115 in turn controls a dispensed fluid volume 1120 of the fluid 207 that can be discharged by the dispenser 110 during a single stroke.
  • the dispensed fluid volume 1120 can be further controlled based on the distance between the surface of the head 317 and the discharge seal 350.
  • FIG. 12 illustrates a dispenser 1200 according to one example that is configured to pump a different volume of fluid than the FIG. 2 dispenser 110 during an individual dispensing stroke.
  • the dispenser 1200 shares a number of features in common with the dispenser 110 described above with respect to FIG. 2. Only the differences between the FIG. 2 dispenser 1 10 and the FIG. 12 dispenser 1200 will be described below.
  • the dispenser 1200 operates in the same manner as described above with respect to the dispenser 110 described in FIGS. 2 and 3.
  • the common components and function will not begin described below, but please refer to the previous discussion.
  • the dispenser 1200 includes a reservoir 1205 and a pump 1210 that are coupled in a reciprocating manner. Referring to FIGS.
  • the dispenser 1200 includes a clip arm 250 that is configured to clip to the clip slot 245 of the carousel 230 and a retention tab 1215 that is configured to be received inside the retention slot 255 of the carousel 230 so as to retain the dispenser 1200.
  • the clip arm 250 and the retention tab 1215 allow the dispenser 1200 to be releasably secured to the carousel 230 in the same manner as described above with reference to FIG. 2.
  • the dispenser 1200 shares a number of components in common with the dispenser 110 of FIGS. 2, 3, and 11.
  • the dispenser 1200 includes the nozzle 215 with the nozzle opening 325, the piston 315 with the head 317, the return spring 330, the val ve members 340, the seal 337, and the valve seat 345 of the type described before, to name just a few examples.
  • the dispenser 1200 of FIG. 13 and the dispenser 110 of FIG. 3 share other components.
  • the dispenser 110 of FIG. 3 and the dispenser 1200 of FIG. 13 generally share all of the same components unless expressly stated otherwise, and the FIG. 3 dispenser 110 and the FIG. 13 dispenser 1200 operate in the same manner.
  • a couple of components have been modified to adjust the volume of the fluid 207 dispensed from the dispenser 1200.
  • the dispenser 1200 has been modified to reduce the volume of the fluid 207 dispensed.
  • the dispenser 1200 in FIG. 12 and 13 has been designed to reduce the volume of the fluid 207 dispensed during the down stroke from a nominal value of about 96 microliters (96 ⁇ l) found in the FIG. 3 dispenser 110 to a nominal value of about 75 microliters (75 ⁇ l) in the FIG. 13 dispenser 1200.
  • the height of the barrel stopper is increased so as to reduce the stroke length and a spacer, such as in the form of a polypropylene tube, is inserted between the lower discharge seal and the valve seat or ball insert.
  • a spacer such as in the form of a polypropylene tube
  • the dispenser 1200 in FIG. 13 includes a stroke limiter 1305 that has been lengthened in order to reduce the stroke length, a discharge seal 1310 that has been lengthened to reduce the volume of the fluid 207 to be dispen sed, and a spacer 1315 received inside the discharge seal 1310 to help further reduce the volume of fluid dispensed.
  • a stroke limiter 1305 that has been lengthened in order to reduce the stroke length
  • a discharge seal 1310 that has been lengthened to reduce the volume of the fluid 207 to be dispen sed
  • a spacer 1315 received inside the discharge seal 1310 to help further reduce the volume of fluid dispensed.
  • the stroke limiter 1305 and discharge seal 1310 are constructed in a similar fashion as the stroke limiter 335 and discharge seal 350 of the FIG. 3 dispenser 110, but the relati ve dimensions of various parts of the stroke limiter 1305 and discharge seal 1310 have been modified to adjust the dispensed volume of fluid 207 dispensed from the dispenser 1200 of FIG. 13.
  • FIG. 14 shows an enlarged cross-sectional view of the pump 1210 of the dispenser 1200.
  • the stroke limiter 1305 has been lengthened in order to reduce the stroke length of the pump 1210.
  • FIG. 15 shows a perspective view of the stroke limiter 1305. Referring to FIGS.
  • the reservoir 1205 includes a stop ridge 1405 that is configured to contact a stroke limit edge 1410 of the stroke limiter 1305 during a dispensing stroke of the pump 1210
  • the stroke limiter 1305 includes a body 1415, a spring retainer flange 1420 that is disposed opposite to the stroke limit edge 1410 at the end of the body 1415, and a seal retainer flange 1425 that is configured to retain the seal 337 surrounding the piston 315.
  • the stroke limiter 1305 has an overall barrel shape that is hollow so as to receive the piston 315.
  • the spring retainer flange 1420 extends in a radially outward direction from one end of the stroke limiter 1305.
  • the body 1415 extends from the spring retainer flange 1420 towards the end where the stroke limit edge 1410 is located.
  • FIG. 16 shows a top view of the stroke limiter I 305.
  • FIG. 17 shows a cross-sectional view of the stroke limiter 1305 as taken along line 17-17 in FIG. 16.
  • the stroke limiter 1305 in FIG. 17 is taller than the stroke limiter 335 in the FIG. 3 dispenser 1 10 so as to reduce the stroke length.
  • the stroke limiter 1305 has a height 1705 as defined between the end surfaces of the stroke limit edge 1410 and the spring retainer flange 1420.
  • the height 1705 of the stroke limiter 1305 is about 12.0 mm with a tolerance of about T 0,08 mm (0.473 ⁇ 0.003 inches).
  • a stroke length 1805 of the dispenser 1200 is defined between the outer surface of the stop ridge 1405 of the reservoir 1205 and the outer surface of the stroke limit edge 1410 of the stroke limiter 1305.
  • the stroke length 1805 has a resulting length of about 5.078 mm (0.1999 inches). The resulting shorter stroke length 1805 causes the dispenser 1200 to dispense the fluid 207 with smaller dispensing volumes per individual stroke,
  • the dispenser 1200 has a pump chamber 1905 defined between the head 317 of the piston 315 and the surface of the discharge seal 1310. As alluded to before, the pump chamber 1905 is dimensioned so as to reduce the volume of the fluid 207 dispensed from the dispenser 1200. As compared to the discharge seal 350 in FIG. 3, the discharge seal
  • the pump chamber 1905 in FIG. 19 is taller such that the discharge seal 1310 extends further into the pump chamber 1905 so as to reduce the dispensed volume of the fluid 207.
  • the pump chamber 1905 in the illustrated example has a generally cylindrical shape, but in other examples, the pump chamber 1905 can be shaped differently.
  • the pump chamber 1905 has a chamber height 1910 defined between the outer surface of the head 317 of the piston 315 and the outer surface of the discharge seal 1310. In one example, the pump chamber 1905 has the chamber height 1910 of about 4.935 mm (0.1934 inches ).
  • the pump chamber 1905 further has a chamber diameter 1915 so as to define the volume of the pump chamber 1905 along with the chamber hei ght 1910.
  • the dispenser 1200 further includes the spacer 1315 that is received inside the discharge seal 1310.
  • the spacer 1315 in one example is in the form of a plastic tube, such as a polypropylene tube.
  • the spacer 1315 defines a thickness 2105. In one example the thickness 2105 of the spacer 1315 is about 1 .4 mm (0.054 inches).
  • FIG. 22 shows a side-by-side comparison of the pump 210 of FIG. 2 and the pump 1210 of FIG. 12.
  • the FIG. 2 pump 210 has the pump chamber 310 with the volume of about
  • the FIG. 12 pump 1210 has the pump chamber 1905 with a volume of about 98.8924 microliters.
  • the pump chamber 310 in the FIG. 2 pump 210 has a chamber height 2205 that is about 6.037 mm (0.2483 inches).
  • the pump cham ber 1905 of the FIG. 12 pump 1210 has the chamber height 1910 of about 4.928 mm (0.1940 inches). With the chamber height 1910 in the FIG. 12 pump chamber 1905 being shorter than the chamber height 2205 in the FIG. 2 pump chamber 310, the FIG. 12 pump 1210 dispenses smaller amounts of fluid during each dispensing stroke.
  • the lower volumes from dispensing allow greater flexibility in the types and amounts of fluid that can be dispensed from the dispenser 1200 of FIG. 12.
  • FIG. 23 illustrates another example of a syringe dispenser system 2300 that can be used in the system 100 of FIG. 1.
  • the syringe dispenser system 2300 in the illustrated example includes a syringe 2305 and a dispenser clip 2310 that is clipped to the syringe 2305 in order to support the syringe 2305 during dispensing of fluid from the syringe 2305.
  • the syringe 2305 includes a barrel 2315, a plunger 2320 that is slidably disposed inside of the barrel 2315, and a nozzle 2325 from which the fluid 207 is dispensed from the syringe 2305.
  • the syringe 2305 is in the form of a 1 milliliter syringe, but the syringe 2305 in other examples can be sized differently to dispense more or less fluid.
  • the nozzle 2325 is in the form of a hollow plastic tube, but in other examples the nozzle 2325 can be in the form of a metal needle or take other forms.
  • the dispenser clip 2310 includes a clip body 2330 and one or more clip arms 2335 extending from the clip body 2330 that are clipped to the barrel 2315 of the syringe 2305. Referring to FIGS. 2 and 23, the syringe dispenser system 2300 is detachably secured in the carousel 230 of the system 100.
  • the dispenser clip 2310 helps to stabilize the syringe 2305 within the carousel 230.
  • the arm 135 presses against the plunger 2320 until the appropriate volume of fluid is dispensed, it should be recognized, the stroke length of the arm 135 can be adjusted so as to adjust the vol ume of fluid dispensed from the syringe 2305.
  • FIG. 24 illustrates a further example of a syringe dispenser system 2400 that can be incorporated into the FIG. 1 system 100.
  • the syringe dispenser system 2400 includes the syringe 2305 that is supported by a syringe adapter 2405.
  • the syringe adapter 2405 incl tides an insert 2410 in which the barrel 2315 of the syringe 2305 is inserted and a carousel adapter 2415.
  • the insert 2410 is in the form of a foam insert, but the insert 2410 in other examples can come in other forms.
  • the insert 2410 defines a syringe opening 2420 in which the syringe 2305 extends through the syringe adapter 2405.
  • the insert 2410 is received in the carousel adapter 2415 that is configured to secure the syringe 2305 io the carousel 230.
  • the carousel 230 has the dispenser cavity 235 and the clip notch 240.
  • the syringe adapter 2405 includes the clip arm 250 that is configured to clip the syringe adapter 2405 into the clip notch 240 of the carousel 230.
  • the carousel adapter 2415 further includes the retention tab 1215 of the type illustrated in FIG. 12. The retention tab 1215 is configured to be inserted into the retention slot 255 of the carousel 230 so as to retain the carousel adapter 2415 within the carousel 230.
  • the carousel 230 further defines a nozzle opening 2425 through which the nozzle 2325 of the syringe 2305 extends to the other side of the carousel 230 so as to be able to dispense the fluid 207 from the syringe 2305.
  • the arm 135 presses against the plunger 2320 until the appropriate volume of fluid is dispensed. It should be recognized, the stroke length of the arm 135 can be adjusted so as to adjust the volume dispensed from the syringe 2305,
  • the carousel 230 can be indexed so as to allow other dispensers to dispense reagents or other chemicals,
  • Actuator generally refers to a device that converts energy into motion.
  • the actuator is a type of transducer that takes one form of energy and converts the energy into another form such as by converting electrical energy into mechanical motion.
  • Actuators can be generally categorized into two types, linear actuators and rotary actuators.
  • Linear actuators produce linear motion such as in the case of moving a piston rod.
  • Rotary actuators produce rotary motion such as in the case of a shaft of an electric motor.
  • Some common types of actuators include electric motors, pneumatic cylinders, hydraulic cylinders, solenoids, and piezoelectric actuators, to name just a few examples.
  • Check Valve or "One-Way Valve” generally refers to a device that mainly permits fluid flow in one direction. Typically, but not always, check valves have two ports, one where the fluid enters and the other where the fluid is discharged.
  • Check valves can generally be categorized in two ways, mechanical type cheek valves and non-mechanical type check valves. With mechanical one-way valves, a mechanical structure, such as a flap or spring- loaded disc, prevents the fluid from flowing in the opposite direction, Non-mechanical type one-way valves uses the fluid flow to prevent reverse fluid flow.
  • One-way valves include ball check valves, flapper valves, duckbill valves, diaphragm valves, membrane valves, elastomeric check valves, fluidic cheek valves, and piezoelectric check valves, to name just a few.
  • Controller generally refers to a device, using mechanical, hydraulic; pneumatic electronic techniques, and/or a microprocessor or computer, which monitors and physically alters the operating conditions of a given dynamical system.
  • the controller may be configured to control the beha vior of another mechanical and/or electronic device.
  • a controller may include a “control circuit” configured to provide signals or other electrical impulses that: may be received and interpreted by the controlled device to indicate how the controlled device should behave.
  • a controller may include a processor for performing calculations to process input or output.
  • a controller may include a memory for storing values to be processed by the processor, or for storing the results of previous processing.
  • a controller may also be configured to accept input and output from a wide array of input and output devices for receiving or sending values.
  • a controller may also be a virtual computing platform having an unknown or fluctuating number of physical processors and memories or memory devices. A controller may thus be physically located in one geographical location or physically spread across several widely scatered locations with multiple processors l inked together by a communication network to operate as a single controller.
  • Electric Motor generally refers to an electrical machine that converts electrical energy into mechanical energy. Normally, but not always, electric motors operate through the interaction between one or more magnetic fields in the motor and winding currents to generate force in the form of rotation. Electric motors can be powered by direct current (DC) sources, such as from batteries, motor vehicles, and/or rectifiers, or by alternating current (AC) sources, such as a power grid, inverters, andfor electrical generators.
  • DC direct current
  • AC alternating current
  • An electric generator can (but not always) be mechanically identical to an electric motor, but operates in the reverse direction, accepting mechanical energy and converting the mechanical energy into electrical energy.
  • Fluid generally refers to a substance that does not have a fixed shape.
  • a fluid includes a liquid and/or a gas.
  • fluids are able to flow easily, such as air flowing over a wing, blood flowing through a circulatory system, water flowing through plumbing, or oil flowing through a motor as examples, in some eases, a fluid refers to a mixture of solids, liquids, and/or gases.
  • a slurry of solids and water, liquid droplets mixed with air, aerated solid particles, a mixture of solids with liquids and gases, andfor other mixtures of different materials may be fluids.
  • Foam generally refers to materials formed by trapping pockets of gas in a liquid or solid. Solid foams are generally categorized as open-cell-structured foams or closed-cell-structured foams. Open-cell-s fascitured foams contain an interconnected ne twork of pores, whereas closed-cell-structured foams do not have interconnected pores. Certain closed-cell-structured foams, sometimes called syntactic foam, contain hollow particles or beads embedded in the matrix of the material.
  • Gear Train generally refers to a system of gears that transmit power from one mechanical component to another.
  • a gear train can include a combination of two or more gears, mounted on rotating shafts, to transmit torque and/or power.
  • the gear train for instance can include a planetary gearset.
  • Each memory may include one or more types of solid-state electronic memory, magnetic memory, or optical memory, just to name a few.
  • each memory may include solid-state electronic Random Access Memory (RAM), Sequentially Accessible Memory (SAM) (such as the First-In, First-Out (FIFO) variety or the Last-In-First-Out (LIFO) variety), Programmable Read Only Memory (PROM), Electronically Programmable Read Only Memory (EPROM), or Electrically Erasable
  • RAM solid-state electronic Random Access Memory
  • SAM Sequentially Accessible Memory
  • PROM Programmable Read Only Memory
  • EPROM Electronically Programmable Read Only Memory
  • EEPROM Electrically Error Read Only Memory
  • optical disc memory such as a DVD or CD ROM
  • magnetically encoded hard disc, floppy disc, tape, or cartridge media or a combination of any of these memory types.
  • each memory may be volatile, nonvolatile, or a hybrid combination of volatile and nonvolatile varieties.
  • Motor generally refers to a machine that supplies motive power for a device with moving parts.
  • the motor can include rotor and linear type motors.
  • the motor can be powered in any number of ways, such as via electricity, internal combustion, pneumatics, and/or hydraulic power sources.
  • the motor can include a servomotor, a pneumatic motor, an electric motor, a hydraulic motor, a steam engine, a pneumatic piston, a hydraulic piston, and/or an internal combustion engine.
  • Opening generally refers to a space or hole that something can pass through.
  • processor generally refers to one or more electronic components configured to operate as a single unit configured or programmed to process input to generate an output.
  • a processor may have one or more components located remotely relative to the others.
  • One or more components of each processor may be of the electronic variety defining digital circuitry, analog circuitry, or both.
  • each processor is of a con ventional, integrated circuit microprocessor arrangement.
  • the concept of a "processor" is not limited to a single physical logic circuit or package of circuits but includes one or more such circuits or circuit packages possibly contained within or across multiple computers in numerous physical locations. In a virtual computing environment, an unknown number of physical processors may be actively processing data, and the unknown number may automatically change over time as well.
  • processor includes a device configured or programmed to make threshold comparisons, rules comparisons, calculations, or perform logical operations applying a rule to data yielding a logical result (e.g., "true” or "false "). Processing activities may occur in multiple single processors on separate servers, on multiple processors in a single server with separate processors, or on multiple processors physically remote from one another in separate computing devices.
  • Pump generally refers to a machine that moves fluids, such as gases, liquids, and/or slurries, by mechanical action.
  • the pump is manually powered by a human or automatically powered through energy source like electrical energy.
  • energy source like electrical energy.
  • pumps are used to move fluids to different places and/or to increase pressure of the fluid.
  • Some common pump types include centrifugal pumps, positive displacement pumps, axial flow pumps, and gravity pumps.
  • Resolver generally refers to a type of rotary sensor for measuring the degree of rotation, velocity, and/or acceleration of a rotary type device.
  • the resolver includes a rotary electrical transformer used for measuring degrees of rotation such as in an electric motor, an electric generator, and/or a transmission.
  • the resolver can include analog or digital type electrical devices.
  • the resolver can be in the form of a two-pole type resolver or a multi- pole type resolver. Some other types of resolvers include receiver type resolvers and differential type resolvers.
  • Sensor generally refers to an object whose purpose is to detect events and/or changes in the environment of the sensor, and then provide a corresponding output.
  • Sensors include transducers that provide various types of output, such as electrical and/or optical signals.
  • the sensors can include pressure sensors, ultrasonic sensors, humidity sensors, gas sensors, motion sensors, acceleration sensors, displacement sensors, force sensors, optical sensors, and/or electromagnetic sensors.
  • the sensors include barcode readers, RFID readers, and/or vision systems.
  • the spring generally refers to an elastic, object that stores mechanical energy.
  • the spring can include a resilient device that can be pressed, pulled, and/or twisted but returns to its former shape when released.
  • the spring can be made from resilient or elastic material such as metal and/or plastic.
  • the spring can counter or resist loads in many forms and apply force at constant or variable levels.
  • the spring can include a tension spring, compression spring, torsion spring, constant spring, and/or variable spring.
  • the spring can take many forms such as by being a flat spring, a machined spring, and/or a serpentine spring.
  • the springs can include various coil springs, pocket springs, Bonnell coils, offset coils, continuous coils, cantilever springs, volute springs, hairsprings, leaf springs, V-springs, gas springs, leaf springs, torsion springs, rubber bands, spring washers, and/or wave springs, to name just a few.
  • Stepper Motor generally refers to a type of electric motor that rotates in a series of small, discrete angular steps.
  • the stepper motor is a brushless direct current (DC) electric motor that divides a full rotation into discrete equal steps.
  • the stepper motor operates by energizing in sequence a series of coils to attract a permanent magnet.
  • the stepper motor is typically configured to move and hold the rotor at one of the discrete angular steps without the need for a position sensor.
  • a stator of the stepper motor includes multiple toothed electromagnets arranged around a rotor in the form of a gear-shaped permanent magnet, A train of input pulses, such as in the form of square waves, can be used to precisely increment the rotational position of the rotor.
  • Stepper motors can be categorized as permanent magnet, variable reluctance, and hybrid synchronous type stepper motors.
  • “Syringe” generally refers to a type of reciprocating pump that includes a plunger or piston fited in a sealing manner within a barrel. In traditional designs, plungers are typically used to pump a fluid, but in some cases, pistons within the syringe are instead used to pump the fluid.
  • the barrel is in the form of a hollow cylindrical body in which the plunger or piston is slidably received so as to facilitate the reciprocating pumping action.
  • the plunger or piston is snugly fitted within the barrel.
  • pushing the plunger creates pressure in a fluid contained in the barrel so as to inject or otherwise discharge the fluid from the barrel through a needle or nozzle.
  • pulling the plunger reduces the pressure inside the barrel so as to draw the fluid into the barrel via the needle or nozzle.
  • the syringe in some cases may include a needle hub to which the needle is attached.
  • the needle hub includes a mechanism to secure the needle such as a luer lock type connection.
  • the syringe includes a nozzle in place of the needle.
  • the nozzle is typically used to dispense liquids without piercing skin or other materials.
  • the needle or nozzle extend from an end of the barrel that is opposite to the plunger.
  • Syringes can be made from of a wide variety of materials including, but not limited to, plastic, glass, rubber, and/or metal. Some common types of syringes include hypodermic syringes, oral syringes, insulin syringes, and irrigation syringes, to name just a few examples. Syringes can be used in a number of applications, such as for medical, scientific, and/or industrial purposes.

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  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Fluid Mechanics (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Coating Apparatus (AREA)

Abstract

Un système de distribution utilise un actionneur pour enfoncer ou actionner autrement un distributeur afin de distribuer un fluide. Dans un mode de réalisation, l'actionneur comprend un moteur pas à pas. Avec le moteur pas à pas, la longueur de course de l'action de pompage utilisée pour distribuer le fluide peut être modifiée et étroitement commandée. Le moteur pas à pas peut fournir une large plage de longueurs de course qui, à son tour, permet au système d'avoir la capacité de distribuer une large plage de volumes de fluide. Pour fournir une commande de rétroaction, le système de distributeur comprend un dispositif de commande et un détecteur de gouttes qui détecte une ou plusieurs propriétés de la goutte distribuée de fluide, telles que le volume. Dans un mode de réalisation, le détecteur de gouttes comprend un rideau à double lumière à travers lequel passe la goutte de fluide distribué. Sur la base des propriétés de gouttes détectées, le dispositif de commande est apte à ajuster la longueur de course de l'action de pompage à partir du moteur pas à pas.
PCT/US2025/012925 2024-02-26 2025-01-24 Actionneur de distributeur de précision Pending WO2025183831A1 (fr)

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Application Number Priority Date Filing Date Title
US202463557659P 2024-02-26 2024-02-26
US63/557,659 2024-02-26

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WO2025183831A1 true WO2025183831A1 (fr) 2025-09-04

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4211003A1 (de) * 1991-04-04 1992-10-08 Olympus Optical Co Vorrichtung und verfahren zum detektieren des volumens einer ausgetragenen fluessigkeit
US20120247612A1 (en) * 2011-03-31 2012-10-04 Fishman Corporation System and Method for Accurately Delivering Controlled Amounts of Viscous Fluid to a Fluid Delivery Device
US20180067142A1 (en) * 2016-08-16 2018-03-08 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Microdispensing device and automatic microdispensing process

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4211003A1 (de) * 1991-04-04 1992-10-08 Olympus Optical Co Vorrichtung und verfahren zum detektieren des volumens einer ausgetragenen fluessigkeit
US20120247612A1 (en) * 2011-03-31 2012-10-04 Fishman Corporation System and Method for Accurately Delivering Controlled Amounts of Viscous Fluid to a Fluid Delivery Device
US20180067142A1 (en) * 2016-08-16 2018-03-08 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Microdispensing device and automatic microdispensing process

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