Handheld device for electrophysiological analysis

• US 9,581,562 B2
• Filed: 02/29/2012
• Issued: 02/28/2017
• Est. Priority Date: 03/01/2011
• Status: Active Grant

• Current Assignee: Sophion Bioscience A/S
• Original Assignee: Sophion Bioscience A/S
• Inventors: Henneke, Jens, Kutchinsky, Jonatan, Byrne, Nicholas, Mathes, Christopher
• Primary Examiner(s): LEONG, SUSAN DANG
• Application Number:
  US14/002,671
• Publication Number:
  US 20130334062A1
• Time in Patent Office: 1,826 Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2300/027 Digital display, e.g. LCD, LED
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: G01N 27/28 Electrolytic cell components
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10

Abstract

A handheld device for analysis of electrophysiological properties of a cellular membrane ion channel in an ion channel containing lipid cellular membrane includes a handheld body with a pump, an electronic controller, and a disposable pipette tip including a pathway for fluid. The pathway connects an open end of the pipette tip to an analysis substrate in the pipette tip. The substrate is adapted to transmit an electrical current through the ion channel. The handheld body and the disposable pipette tip are configured to releasably attach the pipette tip to the body, to provide a hydraulic connection between the pump and the pathway, and to provide an electric connection between the electronic controller and at least one of the electrodes of the substrate. The electronic controller of the handheld body is configured to operate the assembled device for microfluidic analysis of aspirated fluid.

Claims

1. A disposable pipette tip for a handheld device for analysis of electrophysiological properties of a cellular membrane ion channel in an ion channel containing lipid cellular membrane, said handheld device comprising a handheld body with a housing including a pump and an electronic controller, the disposable pipette tip comprising a pathway for fluid, said pathway connecting an open end of the pipette tip to an analysis substrate adapted to transmit an electrical current through the ion channel in said ion channel-containing lipid cellular membrane, when said lipid cellular membrane is held at a predetermined site of the substrate;

the disposable pipette tip being configured to be releasably attached to the body of said handheld device, with the open end of the pipette tip being exposed to an exterior environment, and to provide a hydraulic connection between the pump of the handheld body and said pathway, and to provide an electric connection between the electronic controller and at least one electrode of the substrate.

2. The disposable pipette tip according to claim 1, wherein said substrate is a patch clamp electrode unit, and wherein the at least one electrode comprises electrodes for contacting test solutions.

3. The disposable pipette tip according to claim 2, wherein the pipette tip comprises a laminate structure comprising a plurality of layers, wherein one of said layers comprises the at least one electrode, and wherein another one of said layers comprises at least one flow channel for at least one fluid.

4. The disposable pipette tip according to claim 3, wherein:

a first one of said layers comprises electrodes for contacting internal and external test solutions;

a third one of said layers comprises an external solution layer comprising channels to facilitate the movement of an external test solution on the top surface of said first layer and into a waste reservoir;

a fourth one of said layers comprises an internal solution layer comprising channels to facilitate the movement of said external test solution on the bottom surface of said first layer and into a waste reservoir.

5. The disposable pipette tip according to claim 4, wherein said first layer comprises a printed circuit board.

6. The disposable pipette tip according to claim 4, further comprising a second layer comprising a gasket between said first and said third layers.

7. The disposable pipette tip according to claim 4, wherein a valve is present in said fourth layer to isolate said internal test solution.

8. The disposable pipette tip according to claim 4, wherein said third layer is separated from said fourth layer by a septum.

9. The disposable pipette tip according to claim 1, further comprising a duct for aspirating intracellular fluid into the pipette tip.

10. The disposable pipette tip according to claim 9, wherein said duct is connectable to an external aspirating device when the pipette tip is separate from the handheld body of said handheld device.

11. The disposable pipette tip according to claim 9, wherein said duct is connectable to an aspirating device housed within the handheld body of said handheld device, when the pipette tip is connected to the handheld device.

12. The disposable pipette tip according to claim 9, wherein said duct is provided in an aspiration pipe protruding from the remainder of the pipette tip, and wherein said aspiration pipe is connected to the remainder of the pipette tip through a valve structure.

13. The disposable pipette tip according to claim 12, wherein said valve structure comprises a bending section allowing the aspiration tip to be closed off relative to the remainder of the pipette tip by bending thereof by hand.

14. The disposable pipette tip according to claim 1, wherein said substrate is printed onto a printed circuit board (PCB) carrying electric connectors for the electrodes of the substrate.

15. A handheld device for analysis of electrophysiological properties of a cellular membrane ion channel in an ion channel containing lipid cellular membrane, the device comprising:

a handheld body comprising a housing including a pump and an electronic controller;

a disposable pipette tip according to claim 1;

the handheld body and the disposable pipette tip being configured to releasably attach the pipette tip to the body with the open end of the pipette tip being exposed to an exterior environment, to provide a hydraulic connection between the pump of the handheld body and said pathway, and to provide an electric connection between the electronic controller and at least one electrode of the substrate, the electronic controller of the handheld body being configured to;

operate the pump to aspirate one or more fluids including said ion channel containing lipid cellular membrane into the fluid pathway and substrate of the pipette tip;

determine the electrophysiological properties of the cellular membrane ion channel, while the ion channel containing lipid cellular membrane makes contact with at least one of said electrodes of the substrate, and to simultaneously record current from one of said electrodes; and

output data representative of the recorded current.

16. A method for analysis of electrophysiological properties of a cellular membrane ion channel in an ion channel containing lipid cellular membrane, the method comprising the steps of:

providing a handheld body, the body comprising a housing including a pump and an electronic controller;

providing a disposable pipette tip separate from the body, the pipette tip comprising a pathway for fluid, said pathway connecting an open end of the pipette tip to an analysis substrate adapted to transmit an electrical current through the ion channel in said ion channel-containing lipid cellular membrane, when said lipid cellular membrane is held at a predetermined site of the substrate;

releasably attaching the pipette tip to the body with the open end of the pipette tip being exposed to an exterior environment, the pump of the handheld body hydraulically connected to said pathway, and the electronic controller electrically connected to at least one of said electrodes of the substrate;

operating the pump to aspirate one or more fluids including said ion channel containing lipid cellular membrane into the fluid pathway and substrate of the pipette tip;

determining the electrophysiological properties of the cellular membrane ion channel, while the ion channel containing lipid cellular membrane makes contact with at least one of said electrodes of the substrate, and while the electronic controller records current from one of said electrodes; and

causing the controller to output data representative of the recorded current.

17. The method according to claim 16, wherein an opening at the open end of the pipette tip is larger than the lipid cellular membrane, so as to allow the lipid cellular membrane to be aspirated into the fluid pathway of the pipette tip.