Apparatus for combined assay for current glucose level and intermediate or long-term glycemic control

• US 6,027,692 A
• Filed: 12/12/1996
• Issued: 02/22/2000
• Est. Priority Date: 04/07/1995
• Status: Expired due to Term

• Current Assignee: LXN Corporation (Johnson & Johnson)
• Original Assignee: LXN Corporation (Johnson & Johnson)
• Inventors: Neyer, Gebhard, Galen, Robert S., Hoblitzell, Talei, Burd, John F.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US08/764,320
• Time in Patent Office: 1,167 Days
• Field of Search: 422/55-58, 422/82.05, 422/82.09, 436/87, 436/95, 436/169, 436/170, 356/39, 356/72, 356/73, 356/433-435
• US Class Current: 422/82.05
• CPC Class Codes: C12Q 1/34 involving hydrolase
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: C12Q 2326/12 3,3',5,5'-Tetramethylbenzidine, i.e. TMB
• CPC Class Codes: C12Q 2326/14 Ortho-Tolidine, i.e. 3,3'-dimethyl-(1,1'-biphenyl-4,4'-diamine)
• CPC Class Codes: C12Q 2326/92 Nitro blue tetrazolium chloride, i.e. NBT
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2333/42 Lectins, e.g. concanavalin, phytohaemagglutinin
• CPC Class Codes: G01N 33/526 the element being adapted for a specific analyte
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: Y10S 435/97 Test strip or test slide
• CPC Class Codes: Y10S 436/828 Protein A
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

The present invention is directed to a single test system and method for determining the integrated glycemic condition of a subject by measuring the concentration of glucose and the level of protein-bound glucose in a subject'"'"'s body fluid, such as whole blood. The glucose concentration is indicative of the subject'"'"'s immediate glycemic condition, whereas the protein-bound glucose concentration is indicative of either intermediate or long-term glycemic condition. Optionally, other analytes indicative of glycemic condition, such as ketone bodies or fatty acid derivatives, can also be measured. The present invention also provides a method of diagnosing diabetes. The invention additionally provides a method for analyzing the concentration of fructosamine in less than or equal to five minutes without the use of a reaction accelerator.

Claims

1. An integrated glycemic test system, consisting of

(a) a first strip capable of reacting with glucose in a liquid sample,

(b) a second strip capable of reacting with protein-bound glucose a liquid sample, and

(c) a single device having a spectrophotometer and a single receiving port capable of accepting the first and the second strips when inserted one at a time, so that

(1) when the first strip is inserted into the receiving port, the spectrophotometer measures the glucose reaction on the first strip and the device displays the glucose concentration of the liquid sample, and

(2) when the second strip is inserted into the receiving port, the spectrophotometer measures the protein-bound glucose reaction on the second strip and the device displays the protein-bound glucose concentration of the liquid sample.

2. The test system of claim 1, wherein the protein-bound glucose is fructosamine and wherein the second test strip comprises:

(a) a first plastic substantially planar support member having a sample aperture;

(b) a second plastic substantially planar support member having a detection aperture;

(c) a whole blood separation layer;

(d) a liquid permeable buffer layer containing a buffer having a pH value of between about 10 and about 12; and

(e) an indicator layer containing a nitroblue tetrazolium dye, wherein the separation layer is superposed above the buffer layer and the buffer layer is superposed above the indicator layer and wherein the separation layer, the buffer layer and indicator layer are positioned between the first support member and the second support member, all in fluid contact with the adjacent layer.

3. The test system of claim 1, wherein the device measures both reactions with a single spectrophotometer.

4. The test system of claim 1, wherein the spectrophotometer is capable of measuring at least two different wavelengths.

5. The test system of claim 1, wherein a first LED produces light used to measure the glucose reaction and a second LED produces light to measure the protein-bound glucose reaction.

6. The test system of claim 5, wherein the first LED produces light of a first distinct wavelength and the second LED produces light of a second distinct wavelength.

7. The test system of claim 1, wherein the liquid sample for the first test strip is an unprocessed body fluid sample.

8. The test system of claim 7, wherein the the device measures the glucose reaction by an electrochemical sensor.

9. The test system of claim 7, wherein the first strip comprises reagents to produce a glucose oxidase enzyme reaction.

10. The test system of claim 9, wherein the reagents are dry.

11. The test system of claim 10, wherein the spectrophotometer measures the glucose reaction by changes in reflectance.

12. The test system of claim 1, wherein the liquid sample for the second test strip is an unprocessed body fluid sample.

13. The test system of claim 10, wherein the second strip comprises dry reagents that react with protein-bound glucose.

14. The test system of claim 13, wherein the spectrophotometer measures the protein-bound glucose reaction by changes in reflectance.

15. The test system of claim 12, wherein the protein-bound glucose is fructosamine and wherein the second strip comprises:

(a) a liquid-permeable buffer layer containing a buffer having a pH value of at least 9;

(b) an indicator layer containing an indicator capable of being reduced by fructosamine; and

(c) a support member optionally having a detection aperture;

wherein the buffer layer is adjacent the indicator layer and wherein the buffer layer and indicator layer are supported by the support member.

16. The test system of claim 15, wherein the buffer layer and the indicator layer are juxtaposed.

17. The test system of claim 15, wherein the test device containing the signal producing system further comprises the second strip comprises at least one additional layer in fluid contact with the buffer layer.

18. The test system of claim 17 wherein the additional layer is selected from the group consisting of a blood cell separation layer, a radiation blocking layer, an interference removal layer, a contamination prevention layer, a dialysis layer, a filtering layer, and a support layer.

19. The test system of claim 17, wherein the additional layer is an additional support member having a sample aperture and wherein the buffer layer and the indicator layer are positioned between the support members.

20. The test system of claim 19, wherein the buffer layer is superposed above the indicator layer.