Size Self-Limiting Compositions and Test Devices for Measuring Analytes in Biological Fluids

• US 20090123955A1
• Filed: 12/12/2005
• Published: 05/14/2009
• Est. Priority Date: 12/13/2004
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: MARFURT, Karen L.
• Granted Patent: US 7,964,372 B2
• Time in Patent Office: Days
• US Class Current: 435/10
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: C12Q 1/60 involving cholesterol
• CPC Class Codes: C12Q 1/61 involving triglycerides
• CPC Class Codes: C12Q 1/62 involving uric acid
• CPC Class Codes: G01N 15/00 Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials identification of microorganisms C12Q
• CPC Class Codes: G01N 21/8483 Investigating reagent band test-element handling not specific to a test method G01N33/4875; analytical elements specific to chemical analysis of biological material G01N33/52; autometer with reagent band G01N35/04
• CPC Class Codes: G01N 33/50 Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q
• CPC Class Codes: G01N 33/523 the element being adapted for a specific analyte

Abstract

A test strip or electrochemical sensor for measuring the amount of an analyte in a hiological fluid, e.g., the glucose content of whole blood, includes a size self-limiting reagent formulation employing an enzyme system for reaction with the analyte, the reactive system mixed into a water-soluble swellable polymer matrix containing small water-insoluble particles having a nominal size of about 0.05 to 20 μm, preferably about 1 to 10 μm. The weight ratio of the water-insoluble particles to the water-soluble swellable polymer matrix is about 1/2 to 2/1. The reagent formulation is deposited onto a non-porous substrate to form a thin layer about 6-16 μm thick, providing a rapid and stable response to application of a sample, while being insensitive to the amount of the sample.

Claims

1. A reactive formulation for measuring the amount of an analyte in a biological fluid comprising:

(a) a water-soluble swellable polymer matrix;

(b) water-insoluble particles having a nominal size of about 0.05 to 20 μ

m;

(c) an enzyme system for reacting with said analyte; and

wherein the weight ratio of said water-insoluble particles to said water-soluble swellable polymer matrix is about 1/2 to 2/1.

2. A reactive formulation of claim 1, wherein said enzyme system is formulated to reactive with a member of the group consisting of glucose, lactate, cholesterol, triglycerides, free fatty acids, bilirubin, ascorbate, hydrogen peroxide and uric acid.

3. A reactive formulation of claim 1, wherein said analyte is glucose and the enzyme system includes a member of the group consisting of hexokinase, glucose-6-phosphate dehydrogenase, glucose dehydrogenase, glucose dehydrogenase-PQQ, and glucose oxidase.

4. A reactive formulation of claim 1, wherein said particles are at least one member of the group consisting of titanium dioxide, calcium carbonate, silica, barium sulfate, powdered metals, and latex.

5. A reactive formulation of claim 1, wherein said water-soluble swellable polymer matrix includes at least one member of the group consisting of polyacrylic acid, polyvinyl alcohol, polystyrene sodium sulfonic acid, polyacrylic latex, polyethylene glycol, styrene acrylates, and their co-polymers.

6. A reactive formulation of claim 1, further comprising at least one surfactant, detergent, or thickener.

7. A reactive formulation of claim 1, applied as a coating having a thickness of about 6 to 16 μ

m.

9. A reactive formulation of claim 1, wherein said water-soluble swellable polymer has a molecular weight below about 100,000.

10. A reactive formulation of claim 1, wherein said water-insoluble particles have a nominal size of about 1 to 10 μ

m.

8. (canceled)

11. A method of measuring the amount of an analyte in a biological fluid by applying a sample of said biological fluid to a test strip or electrochemical sensor, said method comprising:

(a) applying a sample of said biological fluid to said test strip or electrochemical sensor, said test strip or electrochemical sensor comprising a non-porous substrate on which is deposited a thin film containing an enzyme system for reacting with said analyte in a formulation including a water-soluble swellable polymer matrix, and water-insoluble particles having a nominal size of about 0.05 to 20 μ

m; and

(b) measuring the response of said sample to said enzyme system by optical or electrochemical methods; and

(c) determining the amount or concentration of said analyte present in said biological fluid.

12. A method of claim 11, wherein said analyte is glucose and said biological fluid is whole blood.

14. A method of claim 11, wherein said thin film has a thickness of about 6 to 16 μ

m.

16. A method of claim 11, wherein the weight ratio of said particles to said polymer matrix is about 1/2 to 2/1.

17. A method of claim 11, wherein said water-soluble swellable polymer matrix is a polymer matrix that includes at least one member of the group consisting of polyacrylic acid, polyvinyl alcohol, polystyrene sodium sulfuric acid, polyacrylic latex, polyethylene glycol, styrene acrylates and their co-polymers.

18. A method of claim 11, wherein said particles are particles that include at least one member of the group consisting of titanium dioxide, calcium carbonate, silica, barium sulfate, powdered metals, and latex.

13. (canceled)

15. (canceled)

19-20. -20. (canceled)

21. A reactive formulation for measuring the glucose content of whole blood comprising

(a) a water-soluble swellable polymer matrix;

(b) water-insoluble particles having a nominal size of about 0.05 to 20 Mm;

(c) an enzyme system for oxidizing said glucose;

(d) an indicator;

wherein the weight ratio of the reflective particles of (b) to the polymer matrix is about 1/2 to 2/1.

22. A reactive formulation of claim 21, wherein said enzyme system includes a member of the group consisting of hexokinase;

glucose-6-phosphate dehydrogenase, glucose dehydrogenase, glucose dehydrogenase-PQQ, and glucose oxidase.

25. A reactive formulation of claim 21, wherein said water-soluble swellable polymer matrix includes at least one member of the group consisting of polyacrylic acid, polyvinyl alcohol, polystyrene sodium sulfuric acid, polyacrylic latex, polyethylene glycol, styrene acrylates, and co-polymers thereof.

23-24. -24. (canceled)

26-31. -31. (canceled)

32. A test strip for measuring the glucose content of whole blood samples comprising:

(a) a substantially non-porous substrate;

(b) a reagent layer disposed on said substrate, said reagent layer comprising;

(1) a water-soluble swellable polymer matrix;

(2) water-insoluble particles having a nominal size of about 0.05 to 20 μ

m;

(3) an enzyme system for oxidizing said glucose, and;

(4) an indicator;

(c) a protective covering for said reagent layer of (b).

(d) an adhesive layer between said reagent layer and said protective covering, said adhesive layer having a capillary channel for receiving said blood sample.

33. A test strip of claim 32, wherein said enzyme system includes a member of the group consisting of hexokinase, glucose-6-phosphate dehydrogenase, glucose dehydrogenase, glucose dehydrogenase-PQQ, and glucose oxidase.

35. A test strip of claim 32, wherein said water-soluble swellable polymer matrix is at least one member of the group consisting of polyacrylic acid, polyvinyl alcohol, polystyrene sodium sulfonic acid, polyacrylic latex, polyethylene glycol, styrene acrylates, and co-polymers thereof.

34. (canceled)

36-43. -43. (canceled)

44. A method of measuring the amount of glucose in a sample of whole blood by applying the blood sample to a test strip, said method comprising:

(a) applying said blood sample to said test strip, said test strip comprising a non-porous substrate on which is deposited a thin film containing an enzyme system for reacting with said glucose in a formulation including a water-soluble swellable polymer matrix, water-insoluble particles having a nominal size of about 0.05 to 20 μ

m, and an indicator; and

(b) measuring the response of said indicators and

(c) determining the amount or concentration of said glucose in said blood sample.

45-52. -52. (canceled)