Electrodes, methods, apparatuses comprising micro-electrode arrays

Abstract

Described are micro-arrays of electrodes disposed proximal to a flexible substrate, electronic components and sensors comprising such arrays, and methods of use for such arrays.

1 . A disposable electrochemical sensor for the detection of an analyte in a liquid sample comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, said reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, wherein the sample-receiving cavity has a volume of less that 1.0 μl and wherein the sensor provides an accurate reading of the amount of analyte in a period of 10 seconds or less.  
     
     
         2 . The sensor of  claim 1 , wherein the reagent layer further comprises an electron transfer mediator.  
     
     
         3 . The sensor of  claim 2  in which the mediator is selected from the group consisting of ferricyanide, osmium (III)-(bipyridyl)-2-imidazolyl-chloride, Meldola blue, [Ru(NH 3 ) 5 pyz] 2 (SO 4 ) 3 , and nitrosoanaline derivatives.  
     
     
         4 . The sensor of  claim 3 , wherein the mediator is nitrosoanaline derivatives.  
     
     
         5 . The sensor of  claim 3 , wherein the mediator is ferricyanide.  
     
     
         6 . The sensor of  claim 2  in which the analyte is selected from the group consisting of glucose, cholesterol, HDL cholesterol, triglycerides, lactate, lactate dehydrogenase, pyruvate, alcohol, uric acid, and 3-Hydroxybutyric acid  
     
     
         7 . The sensor of  claim 6 , wherein the analyte is glucose.  
     
     
         8 . The sensor of  claim 7  in which the mediator is selected from the group consisting of ferricyanide, osmium (III)-(bipyridyl)-2-imidazolyl-chloride, Meldola blue, [Ru(NH 3 ) 5 pyz] 2 (SO 4 ) 3 , and nitrosoanaline derivatives.  
     
     
         9 . The sensor of  claim 8 , wherein the mediator is ferricyanide.  
     
     
         10 . The sensor of  claim 7  in which the enzyme is selected from the group consisting of glucose oxidase, glucose dehydrogenase and diaphorase.  
     
     
         11 . The sensor of  claim 10  in which the enzyme is glucose dehydrogenase.  
     
     
         12 . The sensor of  claim 10  in which the enzyme is glucose oxidase.  
     
     
         13 . The sensor of  claim 10  in which the mediator is selected from the group consisting of ferricyanide, osmium (III)-(bipyridyl)-2-imidazolyl-chloride, Meldola blue, [Ru(NH 3 ) 5 pyz] 2 (SO 4 ) 3 , and nitrosoanaline derivatives.  
     
     
         14 . The sensor of  claim 13 , wherein the mediator is ferricyanide.  
     
     
         15 . The sensor of  claim 1 , wherein the reagent layer is disposed over both the working electrode and the reference electrode.  
     
     
         16 . The sensor of  claim 1 , wherein both the working electrode and the reference electrode are conductive carbon electrodes.  
     
     
         17 . A method of determining the concentration of an analyte in a liquid sample comprising: 
 providing a test sensor including a sample receiving cavity having a volume of less than 1 μl, the sensor including working and counter electrodes disposed within the sample receiving cavity, the sensor further including a reagent layer comprising an enzyme and a mediator, the reagent layer being disposed on at least the working electrode, the enzyme and mediator being selected to react with the analyte to generate an electrochemical signal representative of the concentration of the analyte in the liquid sample;    admitting the liquid sample into the sample receiving cavity;    detecting the time at which the liquid sample enters the sample cavity;    following said detecting, controlling the voltage or current across the working and counter electrodes; and    within ten seconds of said detecting, obtaining a readout of the concentration of the analyte in the liquid sample.    
     
     
         18 . The method of  claim 17  in which said obtaining comprises measuring the electrochemical signal received from the working electrode and determining the concentration of the analyte from the electrochemical signal.  
     
     
         19 . The method of  claim 17  in which said controlling comprises applying a DC voltage of 100-500 mV across the working and counter electrodes, said obtaining comprising measuring the current received from the working electrode and determining the concentration of the analyte from the measured current.  
     
     
         20 . A disposable electrochemical sensor for the detection of an analyte in a liquid sample comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, said reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, wherein the sample-receiving cavity has a volume of less than about 0.4 μl, and wherein the sensor provides an accurate reading of the amount of analyte in a period of 10 seconds or less.  
     
     
         21 . The sensor of  claim 20  in which the sample receiving cavity has a volume of about 0.1 μl to about 0.4 μl.  
     
     
         22 . The sensor of  claim 21  in which the sample receiving cavity has a volume of about 0.1 to about 0.25 μl.  
     
     
         23 . The sensor of  claim 20  in which the sample receiving cavity has a height of about 25 to about 200 μm.  
     
     
         24 . The sensor of  claim 20  in which the sample-receiving cavity has a width of about 1 mm.  
     
     
         25 . The sensor of  claim 20  in which the sample-receiving cavity has a length of about 4 mm.  
     
     
         26 . The sensor of  claim 20  in which the gap between the working and reference electrodes is 15 μm to 50 μm.  
     
     
         27 . The sensor of  claim 20  in which each of the working and reference electrodes has a thickness of 10 μm to 200 μm.  
     
     
         30 . A method for detecting the concentration of an analyte in a liquid sample comprising: 
 providing a disposable electrochemical sensor including a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, the reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, the sample-receiving cavity having a volume of less than about 1 μl;    admitting the liquid sample into the sample chamber;    detecting the application time at which the liquid sample enters the sample chamber;    following said application time, applying a voltage across the working and reference electrodes; and    within ten seconds of said application time, obtaining a readout of the concentration of the analyte in the liquid sample.    
     
     
         31 . The method of  claim 30  in which the sample-receiving cavity has a volume of less than about 0.4 μl.  
     
     
         32 . The sensor of  claim 31  in which the sample receiving cavity has a volume of about 0.1 μl to about 0.4 μl.  
     
     
         33 . The sensor of  claim 32  in which the sample receiving cavity has a volume of about 0.1 to about 0.25 μl.  
     
     
         34 . The sensor of  claim 30  in which the sample receiving cavity has a height of about 25 to about 200 μm.  
     
     
         35 . The method of  claim 30  which includes incubating the liquid sample for an incubation time extending from the application time to said applying a voltage.  
     
     
         36 . The method of  claim 35  in which the incubation time is from about 0.5 seconds to about 6 seconds.  
     
     
         37 . The method of  claim 36  in which the incubation time is about 2 seconds to about 6 seconds.  
     
     
         38 . The method of  claim 37  in which the incubation time is about 3 seconds.  
     
     
         39 . The method of  claim 36  in which the incubation time is about 0.5 seconds.  
     
     
         40 . The method of  claim 30  in which said obtaining a readout comprises obtaining the readout in a test time from about 0.5 to about 2 seconds after said applying a voltage.  
     
     
         41 . The method of  claim 40  in which the test time is 0.5 to 1.5 seconds.  
     
     
         42 . The method of  claim 30  in which said obtaining a readout comprises obtaining the readout less than about 5 seconds after the application time.  
     
     
         43 . The method of  claim 42  in which said obtaining a readout comprises obtaining the readout about 4 seconds after the application time.  
     
     
         44 . The method of  claim 30  in which said applying a voltage comprises applying a voltage of about 100 mV to about 500 mV.  
     
     
         45 . The method of  claim 44  in which said applying a voltage comprises applying a voltage of about 300 mV.  
     
     
         46 . A disposable electrochemical sensor for the detection of an analyte in a liquid sample comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, said reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte, wherein the sample-receiving cavity has a height of about 25 μm to about 200 μm, and wherein the sensor provides an accurate reading of the amount of analyte in a period of 10 seconds or less.  
     
     
         47 . The sensor of  claim 46  in which the sample receiving cavity has a height of about 25 μm to about 100 μm.  
     
     
         48 . The sensor of  claim 46  in which the sample receiving cavity has a height of at least about 100 μm.  
     
     
         49 . The sensor of  claim 48  in which the sample receiving cavity has a height of about 125 μm.  
     
     
         50 . The sensor of  claim 46  in which the sample receiving cavity has a volume of less than about 1 μl.  
     
     
         51 . The sensor of  claim 50  in which the sample receiving cavity has a volume of about 0.1 to about 0.4 μl.  
     
     
         52 . A method for determining the concentration of an analyte in a liquid sample comprising 
 providing a disposable electrochemical sensor comprising a working electrode and a reference electrode disposed within a sample-receiving cavity, a reagent layer disposed within the sample-receiving cavity over at least the working electrode, the reagent layer comprising an enzyme for producing an electrochemical signal in the presence of the analyte;    admitting the liquid sample into the sample receiving cavity;    detecting the application time at which the liquid sample enters the sample chamber;    following said application time, applying a voltage across the working and reference electrodes for a time of less than about 2 seconds; and    within ten seconds of said application time, obtaining a readout of the concentration of the analyte in the liquid sample.    
     
     
         53 . The method of  claim 52  in which said applying a voltage comprises applying a voltage for a time from about 0.5 to about 2 seconds.