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 a cell and an 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,   the cell has electrodes formed in each chamber for receiving an electrical signal developed between the chambers,   the electrical reader unit has a reader circuit operative to measure an electrical signal developed between the chambers of the cell, and   the cell and the 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 . A sensor system according to  claim 1 , wherein the cell and the reader unit have respective connector portions arranged to mate for connection together of the cell and the 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 reader unit.   
     
     
         3 . A sensor system according to  claim 2 , wherein the contacts of the cell and the reader unit are provided on the connector portions of the cell and the reader unit, respectively. 
     
     
         4 . A sensor system according to  claim 2 , wherein the respective connector portions of the cell and the reader unit have are arranged to mate by being plugged together. 
     
     
         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 il to 250 il. 
     
     
         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 im 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 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 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 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. 
     
     
         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 analysing 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 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.   
     
     
         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 a cell 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 for use in measurement of an electrical signal across a lipid bilayer, the cell comprising:
 body elements defining two chambers;   a septum separating the two chambers, the septum comprising a membrane having an aperture capable of supporting a lipid bilayer arranged between the chambers;   electrodes in each chamber for receiving an electrical signal developed between the chambers;   a connector portion arranged to mate with a corresponding connector portion of an electrical reader unit; and   contacts electrically connected to the electrodes for contacting contacts of the electrical reader unit on connection of the cell to an electrical reader unit.   
     
     
         23 . A cell according to  claim 22 , wherein the contacts are provided on the connector portion of the cell. 
     
     
         24 . A cell according to  claim 22 , wherein the connector portion and a corresponding connector portion of an electrical reader unit are arranged to mate by being plugged together. 
     
     
         25 . A cell according to  claim 22 , wherein the chambers each have a volume in the range from 0.1 il to 250 il. 
     
     
         26 . A cell according to  claim 22 , wherein the chambers have a depth of at most 3 mm. 
     
     
         27 . A cell according to  claim 22 , wherein the aperture in the membrane has a diameter in at least one dimension which is 20 im or less. 
     
     
         28 . A cell according to  claim 22 , wherein the electrodes are deposited on the walls of each chamber. 
     
     
         29 . A cell according to  claim 22 , wherein the membrane has a pretreatment effective to increase the affinity of the membrane to a lipid. 
     
     
         30 . A cell according to  claim 22 , wherein one of the chambers contains a gel which extends across the aperture in the membrane. 
     
     
         31 . A cell according to  claim 30 , wherein the gel is a hydrogel. 
     
     
         32 . A cell according to  claim 22 , wherein one of the chambers has a lipid provided on an internal surface thereof. 
     
     
         33 . (canceled) 
     
     
         34 . An electrical reader unit for connection to a cell for measuring an electrical signal across a lipid bilayer formed in the cell, the sensor system, the reader unit comprising:
 connector portions arranged to mate with a corresponding connector portion of a cell;   contacts arranged to make electrical connection with contacts of the cell on connection together of the cell and the reader unit; and   a reader circuit electrically connected to the contacts and operative to measure an electrical signal received from the cell on connection of a cell to the electrical reader unit.   
     
     
         35 . An electrical reader unit according to  claim 34 , wherein the electrical reader unit is portable. 
     
     
         36 . An electrical reader unit according to  claim 34 , 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 a 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. 
     
     
         37 . An electrical reader unit according to  claim 36 , wherein the aperture of the rigid metal body has a maximum dimension of 50 mm or less. 
     
     
         38 . An electrical reader unit according to  claim 34 , wherein the reader circuit comprises:
 an amplifier circuit 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.   
     
     
         39 . An electrical reader unit according to  claim 34 , wherein the electrical reader unit includes a display and is operative to display the electrical signal measured by the reader circuit. 
     
     
         40 . An electrical reader unit according to  claim 34 , wherein the reader circuit is operative to interpret the electrical signal 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.   
     
     
         41 . An electrical reader unit according to  claim 34 , 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. 
     
     
         42 . An electrical reader unit according to  claim 34 , wherein the electrical signal is a current. 
     
     
         43 . A cell for supporting a lipid bilayer, the cell comprising:
 body elements defining two chambers; and   a septum separating the two chambers and comprising a membrane having an aperture capable of supporting a lipid bilayer arranged between the chambers   the body elements on at least one side of the septum comprising a sheet of material fixed with an inner planar surface facing the septum and defining a said chamber having an opening in said inner planar surface aligned with the aperture in the membrane.   
     
     
         44 - 74 . (canceled)