Lipid bilayer sensor system

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.

1 . A sensor system for measuring an electrical signal across a lipid bilayer, the sensor system comprising arrayed cells and an electrical reader unit which are connectable together, wherein the sensor system further comprises an inlet configured for introduction of an aqueous solution to the cells:
 wherein each 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 each cell is configured for containing the aqueous solution:   wherein each cell has electrodes configured 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 any one of the cells, wherein the reader circuit has a microcontroller having an embedded analogue multiplexer; and   wherein each cell and the reader unit are arranged to be connected together to provide electrical connection between the electrodes of each cell and the reader circuit of the electrical reader unit.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . A sensor system according to  claim 1 , wherein the electrical reader unit is portable. 
     
     
         6 . A sensor system according to  claim 1 , wherein the chambers each have a volume in the range from 0.1 μl to 250 μl. 
     
     
         7 . A sensor system according to  claim 1 , wherein the chambers have a depth of at most 3 mm. 
     
     
         8 . A sensor system according to  claim 1 , wherein the aperture in the membrane has a diameter in at least one dimension which is 20 μm or less. 
     
     
         9 . A sensor system according to  claim 1 , wherein the electrodes are deposited on the walls of each chamber. 
     
     
         10 . A sensor system according to  claim 1 , wherein the membrane has a pretreatment effective to increase the affinity of the membrane to a lipid. 
     
     
         11 . A sensor system according to  claim 1 , wherein one of the chambers in each cell contains a gel which extends across the aperture in the membrane. 
     
     
         12 . A sensor system according to  claim 11 , wherein the gel is a hydrogel. 
     
     
         13 . A sensor system according to  claim 1 , wherein one of the chambers in each cell has a lipid provided on an internal surface thereof. 
     
     
         14 . A 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 any one of the cells 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. 
     
     
         15 . A sensor system according to  claim 14 , wherein the aperture of the rigid metal body has a maximum dimension of 50 mm or less. 
     
     
         16 . A sensor system according to  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 analyzing the digital signal.   
     
     
         17 . A 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. 
     
     
         18 . A sensor system according to  claim 1 , wherein the reader circuit is configured to interpret the electrical signal measured thereby by detecting one or more of the following states in any one of the cells 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.   
     
     
         19 . A 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 any one of the cells connected to the electrical reader unit. 
     
     
         20 . A sensor system according to  claim 1 , wherein the electrical signal is a current. 
     
     
         21 . (canceled) 
     
     
         22 . A cell array for use in measurement of an electrical signal across a lipid bilayer, the cell array comprising cells, wherein each cell comprises:
 body elements defining two chambers;   a septum separating the two chambers, the septum comprising a membrane located between the chambers, wherein the membrane has an aperture capable of supporting a lipid bilayer;   electrodes configured for receiving an electrical signal developed between the chambers;   a connector portion configured to mate with a corresponding connector portion of an electrical reader unit; and   contacts electrically connected to the electrodes and configured to connect the cell to the electrical reader unit by contacting contacts of the electrical reader unit.   
     
     
         23 . A cell a according to  claim 22 , 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. 
     
     
         24 . A cell a according to  claim 22 , wherein the connector portions of the cell and the electrical reader unit are arranged to mate by being plugged together. 
     
     
         25 . A cell array according to  claim 22 , wherein the chambers each have a volume in the range from 0.1 μl to 250 μl. 
     
     
         26 . A cell array according to  claim 22 , wherein the chambers have a depth of at most 3 mm. 
     
     
         27 . A cell array according to  claim 22 , wherein the aperture in the membrane has a diameter in at least one dimension which is 20 μm or less. 
     
     
         28 - 49 . (canceled) 
     
     
         50 . The sensor system according to  claim 1 , wherein the septum further comprises, on at least one side, a support sheet of lesser thickness than the body element, fixed to the membrane, wherein the support sheet has a thickness in the range from 0.1 μm to 1 mm. 
     
     
         51 . (canceled) 
     
     
         52 . The sensor system according to  claim 50 , further comprising an electrode located on a surface of the support sheet internal to one of the chambers. 
     
     
         53 - 74 . (canceled) 
     
     
         75 . The sensor system according to  claim 1 , wherein each cell further comprises a bilayer supported by its respective aperture. 
     
     
         76 . The sensor system according to  claim 75 , wherein the bilayer is a lipid bilayer. 
     
     
         77 . The sensor system according to  claim 75 , wherein the bilayer contains an ion channel that connects the two chambers of the cell. 
     
     
         78 . The sensor system according to  claim 1 , wherein the chambers each have a volume in the range from 0.1 μL to 250 μL. 
     
     
         79 . The sensor system according to  claim 1 , wherein the chambers each have a volume in the range from 56 μL to 250 μL. 
     
     
         80 . The sensor system according to  claim 1 , wherein the chambers each have a depth of at most 3 mm between the septum and a respective closure sheet for each chamber. 
     
     
         81 . The sensor system according to  claim 1 , wherein the surface tension of a liquid, in the chamber of any one of the cells, contains the liquid across an area of the chamber parallel to the septum, such that an interface of the liquid with air in the chamber extends across the depth of the chamber. 
     
     
         82 . The sensor system according to  claim 1 , wherein at least one of the two chambers has an inlet configured for introduction of a sample into the chamber.