Microfluidic devices comprising electrochemical sensors

Abstract

An electrowetting-on-dielectric (EWOD) microfluidic device comprises at least one integrated electrochemical sensor, the electrochemical sensor comprising: a reference electrode; a sensing electrode; and an analyte-selective layer positioned over the sensing electrode. In some embodiments, the electrochemical sensor measures a concentration of an analyte in a fluid sample exposed to the electrochemical sensor based on a potential difference between the reference electrode and the sensing electrode. The first analyte and the second analyte can be selected from a group consisting of K + , Na + , Ca 2+ , Cl - , HCO 3 - , Mg 2+ , H + , Ba 2+ , Pb 2+ , Cu 2+ , I - , NH4 + , (SO4) 2- .

1 . A method of making an integrated electrochemical sensor in an electrowetting-on-dielectric (EWOD) microfluidic device, the method comprising:
 electroplating an electrode metal into a reference electrode receiving space of the EWOD device;   electroplating the electrode metal into a sensing electrode receiving space of the EWOD device;   chemically oxidizing a portion of the electroplated metal in each of the reference electrode receiving space and the sensing electrode receiving space to form an oxidized metal layer over a residual metal layer in each of the reference electrode receiving space and the sensing electrode receiving space; and   depositing an analyte-selective layer on the oxidized metal layer in the sensing electrode receiving space.   
     
     
         2 . The method of  claim 1 , wherein the electroplated electrode metal comprises silver, mercury, iridium, or copper. 
     
     
         3 . The method of  claim 1 , wherein:
 the electroplated electrode metal is Ag; and   hydrochloric acid is used to chemically oxidize the portion of the electroplated Ag to form AgCl; and   the residual metal layer is Ag.   
     
     
         4 . The method of  claim 1 , wherein electroplating the electrode metal into the reference electrode receiving space comprises transferring a metal-containing electroplating solution from a first reservoir of the EWOD microfluidic device to the reference electrode receiving space through electrowetting-on-dielectric microfluidic actuation. 
     
     
         5 . The method of  claim 1 , wherein electroplating the electrode metal into the sensing electrode receiving space comprises transferring a metal-containing electroplating solution from a first reservoir of the EWOD microfluidic device to the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation. 
     
     
         6 . The method of  claim 1 , wherein:
 electroplating the electrode metal into the reference electrode receiving space comprises transferring a metal-containing electroplating solution from a first reservoir of the EWOD microfluidic device to the reference electrode receiving space through electrowetting-on-dielectric microfluidic actuation; and   electroplating the electrode metal into the sensing electrode receiving space comprises transferring a metal-containing electroplating solution from the first reservoir of the EWOD microfluidic device to the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation.   
     
     
         7 . The method of  claim 1 , wherein chemical oxidation is carried out by transferring an oxidizing agent solution from a second reservoir of the EWOD microfluidic device to the reference electrode receiving space and/or the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation. 
     
     
         8 . The method of  claim 7 , wherein the electroplated metal in the reference electrode receiving space and/or the sensing electrode receiving space is contacted with the oxidizing agent solution and the surface of the electroplated metal is oxidized. 
     
     
         9 . The method of  claim 1 , wherein depositing the analyte-specific layer comprises transferring a membrane precursor-containing solution from a third reservoir of the EWOD microfluidic device to the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation. 
     
     
         10 . The method of  claim 9 , wherein solvent of the membrane precursor-containing solution is evaporated after transferring the membrane precursor-containing solution to the sensing electrode receiving space, thereby leaving an analyte-specific layer covering a surface of the sensing electrode. 
     
     
         11 . The method of  claim 1 , wherein:
 electroplating the electrode metal into the reference electrode receiving space comprises transferring a metal-containing electroplating solution from a first reservoir of the EWOD microfluidic device to the reference electrode receiving space through electrowetting-on-dielectric microfluidic actuation;   electroplating the electrode metal into the sensing electrode receiving space comprises transferring a metal-containing electroplating solution from the first reservoir of the EWOD microfluidic device to the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation;   chemical oxidation is carried out by transferring an oxidizing agent solution from a second reservoir of the EWOD microfluidic device to the reference electrode receiving space and/or the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation; and   depositing the analyte-specific layer comprises transferring a membrane precursor-containing solution from a third reservoir of the EWOD microfluid device to the sensing electrode receiving space through electrowetting-on-dielectric microfluidic actuation.   
     
     
         12 . The method of  claim 1 , wherein the at least one integrated electrochemical sensor is an ion sensor. 
     
     
         13 . The method of  claim 12 , wherein the at least one integrated electrochemical sensor is a potentiometric sensor. 
     
     
         14 . The method of  claim 13 , wherein the at least one integrated electrochemical sensor measures a concentration of an analyte in a fluid sample exposed to the at least one integrated electrochemical sensor based on a potential difference between the reference electrode and the sensing electrode. 
     
     
         15 . A method of detecting an analyte, the method comprising:
 providing an electrowetting-on-dielectric (EWOD) microfluidic device, wherein the EWOD microfluidic device comprises at least one reservoir and at least one integrated electrochemical sensor, the electrochemical sensor comprising:
 a reference electrode; 
 a sensing electrode; and 
 an analyte-selective layer positioned over the sensing electrode; and 
   transferring an analyte-containing solution from the reservoir of the EWOD microfluidic device to the electrochemical sensor of the EWOD microfluidic device through electrowetting-on-dielectric microfluidic actuation.   
     
     
         16 . The method of  claim 15  further comprising:
 contacting the reference electrode and the analyte-selective layer of the electrochemical sensor with the analyte-containing solution. 
 
     
     
         17 . The method of  claim 16  further comprising:
 determining an analyte concentration in the analyte-containing solution based on a potential difference between the reference electrode and the sensing electrode. 
 
     
     
         18 . The method of  claim 15 , wherein the electrochemical sensor is made by:
 electroplating an electrode metal into a reference electrode receiving space of the EWOD microfluidic device;   electroplating the electrode metal into a sensing electrode receiving space of the EWOD microfluidic device;   chemically oxidizing a portion of the electroplated metal in each of the reference electrode receiving space and the sensing electrode receiving space to form an oxidized metal layer over a residual metal layer in each of the reference electrode receiving space and the sensing electrode receiving space; and   depositing the analyte-selective layer on the oxidized metal layer in the sensing electrode receiving space.