Continuously chemically enhanced aptamer sensors

Abstract

A device for measuring the concentration of a target analyte in a sample fluid. The device ( 100 ) includes a housing ( 110 ) defining a plurality of chambers including at least a first chamber ( 112 ) and a second chamber ( 114 ). The first chamber includes a sensor fluid ( 132 ) therein, and the second chamber includes a reservoir fluid ( 134 ) therein. A sample fluid area ( 116 ) is also defined by the housing. This sample fluid area is capable of receiving a sample fluid ( 130 ) to be tested for the presence or concentration of a target analyte. A first element ( 140 ) separates the first chamber from the sample fluid area and restricts diffusion of solutes between the sensor fluid and sample fluid. A second element ( 142 ) separates the first chamber from the second chamber and restricts diffusion of solutes between the sensor fluid and the reservoir fluid. The device also includes at least one sensing electrode ( 120 ) that is positioned in the sensor fluid.

What is claimed is: 
     
         1 . A device for measuring the concentration of a target analyte in a sample fluid comprising:
 a. a housing defining a plurality of chambers including at least a first chamber and a second chamber, the first chamber including a sensor fluid therein, and the second chamber including a reservoir fluid therein;   b. a sample fluid area defined by the housing, the sample fluid area capable of receiving a sample fluid;   c. a first element that separates the first chamber from the sample fluid area and restricts diffusion of solutes between the sensor fluid and sample fluid;   d. a second element that separates the first chamber from the second chamber and restricts diffusion of solutes between the sensor fluid and the reservoir fluid; and   e. at least one sensing electrode positioned in the sensor fluid.   
     
     
         2 . The device of  claim 1 , wherein the sensor fluid contains a plurality of aptamers. 
     
     
         3 . The device of  claim 2 , further comprising a plurality of tags associated with the plurality of aptamers, the plurality of tags selected from the group consisting of redox tags and optical tags. 
     
     
         4 . The device of  claim 1 , wherein the at least one sensing electrode contains a plurality of aptamers. 
     
     
         5 . The device of  claim 4 , further comprising a plurality of tags associated with the plurality of aptamers, the plurality of tags selected from the group consisting of redox tags and optical tags. 
     
     
         6 . The device of  claim 1 , wherein the reservoir fluid contains at least one enhancing solute. 
     
     
         7 . The device of  claim 6 , wherein the at least one enhancing solute is selected from the group consisting of a buffer, a salt, an antioxidant, an inhibitor, and a molecule that passivates the sensing electrode. 
     
     
         8 . The device of  claim 6 , wherein any restriction on the diffusion of the at least one enhancing solute from the reservoir fluid to the sensor fluid provided by the second element is less than any restriction on the diffusion of the at least one enhancing solute from the sensor fluid to the sample fluid provided by the first element. 
     
     
         9 . The device of  claim 8 , wherein the at least one sensor enhancing solute is partially retained in the sensor solution. 
     
     
         10 . The device of  claim 1 , further comprising a passivating layer of molecules on the at least one sensing electrode. 
     
     
         11 . The device of  claim 10 , wherein the passivating layer includes a monolayer of mercaptohexanol. 
     
     
         12 . The device of  claim 1 , wherein the sensor fluid includes at least one solute harmful to the at least one sensing electrode, wherein the second element is adapted to allow the at least one solute harmful to the at least one sensing electrode to diffuse from the sensor fluid into the reservoir fluid. 
     
     
         13 . The device of  claim 12 , wherein the harmful solute in the reservoir fluid is at a first concentration and the harmful solute in the sensor fluid is at a second concentration, wherein the first concentration is lower than the second concentration in an amount selected from the group consisting of greater than 2×, less than 10×, and less than 100×. 
     
     
         14 . The device of  claim 1 , wherein the sample fluid includes at least one solute harmful to the at least one sensing electrode, wherein the harmful solute has a lower total mass transport through first element than through second element such that if it enters the sensor fluid it will be removed into the reservoir fluid. 
     
     
         15 . The device of  claim 1 , wherein the target analyte in the sample fluid is at a first concentration, and the target analyte in the sensor fluid is at a second concentration, wherein the first concentration and second concentration differ by an amount chosen from less than 5%, less than 10%, and less than 50%. 
     
     
         16 . The device of  claim 1 , wherein the first element that separates the first chamber from the sample fluid area and restricts diffusion of solutes between the sensor fluid and sample fluid is chosen from a channel, a membrane, and a hydrogel. 
     
     
         17 . The device of  claim 16 , wherein the first element is a membrane chosen from a liquid filled membranes, an oil-membrane, a filtration membrane, and a size-selective membranes 
     
     
         18 . The device of  claim 16 , wherein the first element is a membrane, and the membrane at least partially retains at least one sensor enhancing solute in the sensor solution. 
     
     
         19 . The device of  claim 1 , wherein the second element that separates the first chamber from the second chamber and restricts diffusion of solutes between the sensor fluid and the reservoir fluid is chosen from a channel, a membrane, and a hydrogel. 
     
     
         20 . The device of  claim 19 , wherein the second element is a membrane, and the membrane includes polyethersulfone (PES). 
     
     
         21 . The device of  claim 19 , wherein the second element is a hydrogel, and the hydrogel includes agar. 
     
     
         22 . The device of  claim 1 , wherein the volume of the reservoir fluid in the second chamber is greater than the volume of sensor fluid in the first chamber. 
     
     
         23 . The device of  claim 22 , wherein the difference in volume of the reservoir fluid compared to the volume of the sensor fluid is chosen from at least 2× greater, at least 10X greater, at least 50X greater, and at least 250× greater. 
     
     
         24 . The device of  claim 22 , wherein the sensor fluid contains a plurality of aptamers. 
     
     
         25 . The device of  claim 24 , wherein a first mass flow of the plurality of aptamers that occurs at the first element is less than a second mass flow of plurality of aptamers that occurs at the second element. 
     
     
         26 . The device of  claim 25 , wherein the degree by which the first mass flow of the plurality of aptamers is less than the second mass flow of the plurality of aptamers is selected from the group consisting of at least 2× less, at least 10× less, at least 50× less, and at least 250× less. 
     
     
         27 . The device of  claim 25 , wherein a first mass flow of the analyte that occurs at the first element is greater than a second mass flow of the analyte that occurs at the second element. 
     
     
         28 . The device of  claim 27 , wherein the degree by which the first mass flow of analyte is greater than the second mass flow of analyte is selected from the group consisting of at least 2× greater, at least 10× greater, at least 50× greater, and at least 250× greater. 
     
     
         29 . The device of  claim 27 , wherein a concentration of analyte in the sensor fluid will be within at least a percentage of a concentration of analyte in the sample fluid, wherein the percentage is chosen from 50%, 10%, 2%, and 0.4%.