Bilirubin sensor

• US 7,749,766 B2
• Filed: 01/12/2007
• Issued: 07/06/2010
• Est. Priority Date: 01/12/2007
• Status: Active Grant

• Current Assignee: Nova Biomedical Corporation (Nova Chemicals)
• Original Assignee: Nova Biomedical Corporation (Nova Chemicals)
• Inventors: Lauro, Mary M., Young, Chung Chang, Pei, Jianhong
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US11/622,564
• Publication Number:
  US 20080169206A1
• Time in Patent Office: 1,271 Days
• Field of Search: 436/63, 436/70, 436/97, 436/149, 436/150, 436/151, 436/175, 436/177, 422/68.1, 422/82.01, 422/82.02, 204/400, 204/403.01, 204/403.02, 204/403.03, 204/403.04, 204/403.14, 204/411, 204/412, 205/780.5
• US Class Current: 436/97
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: Y10T 436/146666 Bile pigment
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A bilirubin sensor has a working electrode with a first chemical matrix disposed thereon that contains a binder, a substrate electrode with a second chemical matrix dispose thereon that contains a binder and a chemical agent that consumes bilirubin, a reference electrode, a sample chamber containing the working electrode, the substrate electrode and the reference electrode, and a method of measuring bilirubin in a body fluid.

Claims

1. A bilirubin sensor comprising:

a working electrode with a first chemical matrix disposed thereon, the first chemical matrix containing a binder, wherein the first chemical matrix is capable of oxidizing all oxidizable species in a fluid sample;

a substrate electrode with a second chemical matrix disposed thereon, the second chemical matrix containing a binder and a chemical agent that consumes bilirubin, wherein the second chemical matrix is capable of oxidizing all oxidizable species in the fluid sample except bilirubin;

a reference electrode;

a sample chamber containing the working electrode, the substrate electrode and the reference electrode;

means for applying a potential between the reference electrode and the working electrode to obtain a first current;

means for applying a potential between the reference electrode and the substrate electrode to obtain a second current;

means for correlating the first current to a concentration of all oxidizable species in the fluid sample and for correlating the second current to a concentration of all oxidizable species in the fluid sample except bilirubin;

means for subtracting the second current from the first current to obtain a current difference;

and means for correlating the current difference to a concentration of bilirubin in the fluid sample.

2. The bilirubin sensor of claim 1 wherein the chemical agent is an oxidoreductase of bilirubin.

3. The bilirubin sensor of claim 2 wherein the oxidoreductase of bilirubin is bilirubin oxidase.

4. The bilirubin sensor of claim 1 wherein the first chemical matrix and the second chemical matrix contains a chemically oxidizing reagent.

5. The bilirubin sensor of claim 4 wherein said chemically oxidizing reagent is a redox mediator.

6. The bilirubin sensor of claim 4 wherein the chemically oxidizing reagent is selected from the group consisting of potassium ferricyanide, sodium ferricyanide, ferrocene, ferrocene derivatives, cupric sulfate, hexaamineruthenium (III) chloride, hexaamineruthenium (III) chloride derivatives, and osmium complexes.

7. The bilirubin sensor of claim 1 wherein the bilirubin sensor is an amperometry-based sensor.

8. The bilirubin sensor of claim 1 wherein the first chemical matrix and the second chemical matrix includes one or more reagents selected from the group consisting of a bulking agent, a surfactant and a buffer.

9. The bilirubin sensor of claim 8 wherein the buffer has a pH in the range from about 5.0 to about 8.5.

10. The bilirubin sensor of claim 1 wherein the binder includes one or more chemical reagents selected from the group consisting of polyethylene oxide, polyvinyl pyrolidone, starch, methylcellulose, polyvinyl alcohol, carboxy methyl cellulose, and polyamino acids.

11. A bilirubin sensor comprising:

a working electrode with a first chemical matrix disposed thereon, the first chemical matrix containing a whole blood filtering component, wherein the first chemical matrix is capable of oxidizing all oxidizable species in a fluid sample;

a substrate electrode with a second chemical matrix disposed thereon, the second chemical matrix containing a whole blood filtering component and a chemical agent that consumes bilirubin, wherein the second chemical matrix is capable of oxidizing all oxidizable species in the fluid sample except bilirubin;

a reference electrode;

a sample chamber containing the working electrode, the substrate electrode and the reference electrode;

means for applying a potential between the reference electrode and the working electrode to obtain a first current;

means for applying a potential between the reference electrode and the substrate electrode to obtain a second current;

means for correlating the first current to a concentration of all oxidizable species in the fluid sample and for correlating the second current to a concentration of all oxidizable species in the fluid sample except bilirubin;

means for subtracting the second current from the first current to obtain a current difference;

and means for correlating the current difference to a concentration of bilirubin in the fluid sample.

12. The bilirubin sensor of claim 11 wherein the chemical agent is an oxidoreductase of bilirubin.

13. The bilirubin sensor of claim 12 wherein the oxidoreductase of bilirubin is bilirubin oxidase.

14. The bilirubin sensor of claim 11 wherein the first chemical matrix and the second chemical matrix contains a chemically oxidizing reagent.

15. The bilirubin sensor of claim 14 wherein said chemically oxidizing reagent is a redox mediator.

16. The bilirubin sensor of claim 14 wherein the chemically oxidizing reagent is selected from the group consisting of potassium ferricyanide, sodium ferricyanide, ferrocene, ferrocene derivatives, cupric sulfate, hexaamineruthenium (III) chloride, hexaamineruthenium (III) chloride derivatives, and osmium complexes.

17. The bilirubin sensor of claim 11 wherein the bilirubin sensor is an amperometry-based sensor.

18. The bilirubin sensor of claim 11 wherein the first chemical matrix and the second chemical matrix includes one or more reagents selected from the group consisting of a bulking agent, a surfactant and a buffer.

19. The bilirubin sensor of claim 18 wherein the buffer has a pH in the range from about 5.0 to about 8.5.

20. A method of measuring bilirubin in a fluid sample comprising the steps of:

disposing the fluid sample into a sample chamber of a bilirubin sensor;

applying a potential between a reference electrode and a working electrode in the sample chamber, wherein the working electrode has a first chemical matrix disposed thereon that contains a binder and that serves to oxidize all oxidizable species in the fluid sample;

measuring a first current generated between the working electrode and the reference electrode, wherein the first current is correlated to a concentration of all oxidizable species in the fluid sample;

applying a potential between the reference electrode and a substrate electrode in the sample chamber, wherein the substrate electrode has a second chemical matrix disposed thereon that contains a binder and a chemical agent that consumes bilirubin so as to oxidize all oxidizable species in the fluid sample except bilirubin;

measuring a second current generated between the reference electrode and the substrate electrode, wherein the second current is correlated to a concentration of all oxidizable species in the fluid sample except bilirubin;

subtracting the second current from the first current and obtaining a current difference; and

correlating the current difference to a concentration of bilirubin in the fluid sample.

21. The method of claim 20 further comprising:

measuring a resistance value of the fluid sample between the reference electrode and one of the working electrode, the substrate electrode, or both;

applying the resistance value to a first equation and determining the hematocrit level of the fluid sample from the first equation; and

calculating a corrected concentration of bilirubin using a second equation to correct for the presence of hematocrit in the fluid sample.

22. The method of claim 20 wherein the potential applying steps include applying a potential of about 0.800 volts.

23. The method of claim 20 wherein the potential applying steps include applying a potential of about 0.350 volts when the first chemical matrix and the second chemical matrix contains a chemically oxidizing reagent.

24. The method of claim 20 further comprising triggering the current measuring step when the fluid sample contacts the working electrode, the substrate electrode and the reference electrode.

25. The method of claim 20 further comprising:

measuring a resistance value of the fluid sample between the reference electrode and one of the working electrode, the substrate electrode, or both; and

applying the resistance value to a derived algorithm to correct for the presence of hematocrit in the fluid sample.