Lipid bilayer sensor system

• US 10,215,768 B2
• Filed: 06/04/2015
• Issued: 02/26/2019
• Est. Priority Date: 02/20/2007
• Status: Active Grant

• Current Assignee: Oxford Nanopore Technologies Limited
• Original Assignee: Oxford Nanopore Technologies Limited
• Inventors: Sanghera, Gurdial Singh, White, Steven Paul, Reid, Terrence Alan
• Primary Examiner(s): Kessel, Maris R
• Application Number:
  US14/731,104
• Publication Number:
  US 20150268256A1
• Time in Patent Office: 1,363 Days
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

A sensor system (1) for measuring an electrical signal across a lipid bilayer is formed by a cell (2) and an electrical reader unit (3) which are connectable together. The cell (2) is capable of supporting a lipid bilayer across an aperture (11) in a membrane (10) and has a construction which is cheap to manufacture. The reader unit (3) is a portable device which monitors an electrical signal generated in the connected cell (2) to allow analysis of that electrical signal. The sensor system (1) is intended for use outside of a laboratory setting.

Claims

1. A sensor system for measuring an electrical signal across a lipid bilayer, the sensor system comprising a cell and a portable electrical reader unit which are connectable together;

wherein the cell defines two chambers separated by a septum, the septum comprising a membrane having an aperture capable of supporting a lipid bilayer and arranged between the chambers, wherein the chambers each have a volume in the range from 0.1 μ

L to 250 μ

L, and a depth of at most 3 mm between the septum and a respective closure sheet for each chamber,

such that surface tension of a liquid in the chamber contains the liquid across an area of the chamber parallel to the septum, and

such that an interface of the liquid with air in the chamber extends across the depth of the chamber;

wherein the cell has electrodes formed in each chamber for receiving an electrical signal developed between the chambers,

wherein the electrical reader unit has a reader circuit operative to measure an electrical signal developed between the chambers of the cell, and

wherein the cell and the electrical reader unit are arranged to be connected together to provide electrical connection between the electrodes of the cell and the reader circuit of the electrical reader unit.

2. The sensor system according to claim 1, wherein the cell and the electrical reader unit have respective connector portions arranged to mate for connection together of the cell and the electrical reader unit, and

the cell has contacts electrically connected to the electrodes and the electrical reader unit also has contacts electrically connected to the reader circuit, the contacts of the cell and the electrical reader unit being arranged to make electrical connection with each other on connection together of the cell and the electrical reader unit.

3. The sensor system according to claim 2, wherein the contacts of the cell and the electrical reader unit are provided on the connector portions of the cell and the electrical reader unit, respectively.

4. The sensor system according to claim 2, wherein the respective connector portions of the cell and the electrical reader unit have are arranged to mate by being plugged together.

5. The sensor system according to claim 1, wherein the aperture in the membrane has a diameter in at least one dimension which is 20 μ

m or less.

6. The sensor system according to claim 1, wherein the electrodes are deposited on the walls of each chamber.

7. The sensor system according to claim 1, wherein the membrane has a pretreatment effective to increase the affinity of the membrane to a lipid.

8. The sensor system according to claim 1, wherein one of the chambers contains a gel which extends across the aperture in the membrane.

9. The sensor system according to claim 8, wherein the gel is a hydrogel.

10. The sensor system according to claim 1, wherein one of the chambers has a lipid provided on an internal surface thereof.

11. The sensor system according to claim 1, wherein the electrical reader unit further comprises a rigid metal body having a cavity containing the connector portion of the electrical reader unit and being of sufficient size to accommodate the cell when connected to the electrical reader unit, the rigid metal body having an aperture which aperture faces the connector portion of the electrical reader unit and is of sufficient size to allow passage of the cell for connection of the cell to the electrical reader unit.

12. The sensor system according to claim 11, wherein the aperture of the rigid metal body has a maximum dimension of 50 mm or less.

13. The sensor system according claim 1, wherein the reader circuit comprises:

an amplifier for amplifying an electrical signal received at the contacts of the electrical reader unit;

an analog-to-digital converter for converting the amplified electrical signal into a digital signal; and

a microprocessor for receiving and analysing the digital signal.

14. The sensor system according to claim 1, wherein the electrical reader unit includes a display and is operative to display the electrical signal measured by the reader circuit.

15. The sensor system according to claim 1, wherein the reader circuit is operative to interpret the electrical signal measured thereby by detecting one or more of the following states in the cell and producing an output indicative of the detected state, the states being:

1) the chambers in the cell being dry;

2) the chambers in the cell containing an aqueous solution without a lipid bilayer being formed across the aperture in the membrane;

3) a lipid bilayer being formed across the aperture in the membrane without a membrane protein being inserted therein;

4) a lipid bilayer being formed across the aperture in the membrane with a membrane protein being inserted therein without an analyte binding to the membrane protein; and

5) a lipid bilayer being formed across the aperture in the membrane with a membrane protein being inserted therein with an analyte binding to the membrane protein.

16. The sensor system according to claim 1, wherein the electrical reader unit further includes a bias circuit operative to provide a bias to the contacts of the electrical reader unit for supply to a cell connected to the electrical reader unit.

17. The sensor system according to claim 1, wherein the electrical signal is a current.

18. The sensor system according to claim 1, further comprising a bilayer supported by the aperture.

19. The sensor system according to claim 18, wherein the bilayer is a lipid bilayer.

20. The sensor system according to claim 18, wherein the bilayer contains an ion channel that connects the two chambers.

21. The sensor system according to claim 1, wherein the chambers each have a volume in the range from 56 μ

L to 250 μ

L.