Size self-limiting compositions and test devices for measuring analytes in biological fluids
View Patent ↗A test strip or electrochemical sensor for measuring the amount of an analyte in a biological 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.
1. A method of measuring the amount of an analyte in a biological fluid, said method comprising:
(a) applying a sample of said biological fluid to a test strip, said test strip comprising a non-porous substrate on which is deposited a single film comprising 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 μm;
(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.
2. The method of claim 1 , wherein said analyte is glucose and said biological fluid is whole blood.
3. The method of claim 1 , wherein said film has a thickness of about 6 to 16 μm.
4. The method of claim 1 , wherein the weight ratio of said particles to said polymer matrix is about 1/2 to 2/1.
5. The method of claim 1 , 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.
6. The method of claim 1 , wherein said particles include at least one member of the group consisting of titanium dioxide, calcium carbonate, silica, barium sulfate, powdered metals, and latex.
7. The method 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.
8. The method of claim 1 , wherein the film further comprises at least one surfactant, detergent, or thickener.
9. The method of claim 1 , wherein said water-soluble swellable polymer has a molecular weight below about 100,000.
10. The method of claim 1 , wherein said water-insoluble particles have a nominal size of about 1 μm to about 10 μm.
11. The method of claim 1 , wherein the response of said sample is substantially independent of test time.
12. A method of measuring the amount of glucose in a blood sample, 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 film comprising 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 μm, and an indicator, the film having a thickness of about 6 to 16 μm;
(b) measuring the response of said indicator; and
(c) determining the amount or concentration of said glucose in said blood sample.
13. The method of claim 12 , wherein the weight ratio of said particles to said polymer matrix is about 1/2 to 2/1.
14. A method of claim 12 , 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.
15. A method of claim 12 , wherein said particles include at least one member of the group consisting of titanium dioxide, calcium carbonate, silica, barium sulfate, powdered metals, and latex.
16. The method of claim 12 , wherein the enzyme system includes a member of the group consisting of hexokinase, glucose-6-phosphate dehydrogenase, glucose dehydrogenase, glucose dehydrogenase-PQQ, and glucose oxidase.
17. The method of claim 12 , wherein the film further comprises at least one surfactant, detergent, or thickener.
18. The method of claim 12 , wherein said water-soluble swellable polymer has a molecular weight below about 100,000.
19. The method of claim 12 , wherein said water-insoluble particles have a nominal size of about 1 μm to about 10 μm.
20. The method of claim 12 , wherein the response of said indicator is substantially independent of test time.