Dual glucose-hydroxybutyrate analytical sensors

• US 20030068666A1
• Filed: 10/03/2002
• Published: 04/10/2003
• Est. Priority Date: 10/05/2001
• Status: Active Grant

• Current Assignee: Stephen Eliot Zweig
• Original Assignee: Stephen Eliot Zweig
• Inventors: Zweig, Stephen Eliot
• Granted Patent: US 6,984,307 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• 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: C12Q 1/006 for glucose
• CPC Class Codes: G01N 33/523 the element being adapted for a specific analyte
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

Diagnostic dry reagent tests capable of reacting with a single drop of whole blood and reporting both glucose and beta-hydroxybutyrate levels are taught. Such dry reagent tests may employ electrochemical detection methodologies, optical detection methodologies, or both methodologies. These tests help facilitate the early detection of the onset of ketoacidosis in diabetes.

Claims

1. :

A diagnostic dry reagent for the simultaneous enzymatic analysis of two different analytes in a single sample of whole blood, wherein

the first analyte is determined by a first reaction zone, and a second reaction zone, physically separated from the first reaction zone, determines the second analyte;

a fluid bridge formed by the applied sample connects the two reaction zones;

application of a single drop of whole blood hydrates the reaction zones, and initiates the beginning of the test;

excess blood does not have to be manually removed by the user;

and the user does not have to perform a manual timing step.

2. :

The dry reagent device of claim 1, in which the analytes are glucose and beta-hydroxybutyrate.

3. :

The device of claim 2, in which the reagent is an electrochemical reagent, and the reaction detected is an electrochemical reaction, wherein the reagent has at least one electrode for the first reagent, one electrode for the second reagent, and at least one reference electrode.

4. :

The device of claim 3, further employing mathematical deconvolution techniques to correct the beta-hydroxybutyrate signal from the distorting effects of the neighboring glucose signal.

5. :

The device of claim 3, further employing mathematical deconvolution techniques to correct the glucose signal from the distorting effects of the neighboring beta-hydroxybutyrate signal.

6. :

The device of claim 3, in which at least some of the electrodes contain carbon particles.

7. :

The device of claim 3, in which the glucose electrode contains or is associated with a glucose oxidase enzyme and an electron transfer mediator.

8. :

The device of claim 3, in which the glucose electrode contains or is associated with glucose dehydrogenase enzyme and an electron transfer mediator

9. :

The device of claim 3, in which the beta-hydroxybutyrate electrode contains or is associated with beta-hydroxybutyrate dehydrogenase enzyme and an electron transfer mediator.

10. :

The device of claim 3, in which one or more layers of a microporus, microparticle and binder composition, which allows plasma to pass but blocks red cells, cover one or more of the reagent'"'"'s electrodes.

11. , The device of claim 10, in which one or more layers of a microporus;

microparticle and binder composition are rendered microporous through a freeze-drying step.

12. :

The device of claim 10, in which the microporous microparticle composition is composed of spherical particles with a diameter between 0.1 and 50 microns.

13. :

The device of claim 2, in which the reagent is an optical device, and the reaction detected is a colorimetric, fluorescent, or luminescent reaction.

14. :

The device of claim 13, in which the glucose zone of the device contains or is associated with a glucose oxidase enzyme, peroxidase, and a hydrogen peroxide sensitive optical indicator dye.

15. :

The device of claim 13, in which the glucose zone of the device contains or is associated with a glucose dehydrogenase enzyme, NAD, diaphorase, and a NADH sensitive optical indicator dye.

16. :

The device of claim 13, in which the beta-hydroxybutyrate zone of the device contains or is associated with a beta-hydroxybutyrate dehydrogenase enzyme, NAD, diaphorase, and a NADH sensitive optical indicator dye.

17. :

The device of claim 13, in which a chemical detection means is incorporated into at least one of the sensor reaction zones, and in which the chemical detection means changes its calorimetric, fluorescent, or luminescent state upon contact with the liquid sample.

18. :

The device of claim 17, in which the increase in reflectance on at least one wavelength of the chemical detection means is used to trigger the start of an automated meter system that monitors the reaction optically.

19. :

The diagnostic reagent of claim 1, in which the first analyte produces an electrochemical signal, and in which the second analyte produces a detectible change in an optical signal.

20. The diagnostic reagent of claim 19, in which the diagnostic reagent contains conducting electrodes to transmit the electrochemical signal, and an optical wave guide to transmit the optical signal.

21. :

The diagnostic reagent of claim 20, in which the optical wave guide is a single optical fiber.

22. :

A meter for use with a diagnostic dry reagent for the simultaneous enzymatic analysis of two different analytes in a single 1-20 ul sample of whole blood, wherein the first analyte is determined by a first reaction zone, the second analyte is determined by a second reaction zone physically separated from the first reaction zone, and wherein the two reaction zones are connected by a fluid bridge formed by the applied sample, and

wherein application of the sample of whole blood both hydrates the reaction zones, and initiates the beginning of the test,

wherein the meter initiates data collection upon application of sample to the reagent, and

wherein the meter collects a plurality of data points from both reaction zones, processes the data, and returns the value of both analytes to the user.

23. :

The meter of claim 22, in which the first analyte is glucose, and the second analyte is beta-hydroxybutyrate.

24. :

The meter of claim 22, in which the reagent is an electrochemical reagent and the meter reads data from the reagent through electrical voltage and current measuring means.

25. :

The meter of claim 22, in which the reagent is a calorimetric reagent and the meter reads data from the reagent through reflectance photometry.

26. :

The meter of claim 22, in which the reagent is a fluorescent reagent, and the meter reads data from the reagent through fluorescence spectroscopy.

27. :

The meter of claim 22, in which the reagent is a luminescent reagent, and the meter reads data from the reagent through luminescence photometry.

28. :

The meter of claim 22, in which the reagent is an electrochemical reagent and the meter reads data from the reagent through electrical voltage and current measuring means.

29. :

The meter of claim 22, in which the reagent is a calorimetric reagent and the meter reads data from the reagent through reflectance photometry.

30. :

The meter of claim 25, in which the meter photometer periodically monitors the reagents reflectance at one or more defined wavelengths, and initiates data collection for a variable length test upon detecting a reflectance increase in the reagent.

31. :

A triggering method to initiate the start of an optical dry reagent test device, said triggering method comprising;

a tracking dye composition on the dry reagent test device that increases reflectance on at least one wavelength upon contact with an applied sample;

an automated photometric system that performs a series of readings upon the tracking dye;

wherein upon contact with a fluid sample, the dye composition increases reflectance on at least one wavelength, which is detected by an automated photometric system and used to initiate the start of data acquisition for the test.

32. :

An electrical triggering method to initiate the start of an optical dry reagent test device, wherein upon contact with a fluid sample, an amperometric, potentiometric, conductometric, or impedence change in the electrical characteristics of the reagent is detected by an automated system, and used to initiate the start of optical data acquisition for the test.