Minimum procedure system for the determination of analytes

• US 20030073153A1
• Filed: 06/24/2002
• Published: 04/17/2003
• Est. Priority Date: 08/13/1986
• Status: Active Grant

• Current Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Phillips, Roger, McGarraugh, Geoffery, Jurik, Franklin A., Underwood, Raymond D.
• Granted Patent: US 6,887,426 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 2021/4757 Geometry 0/45° or 45/0°
• CPC Class Codes: G01N 21/314 with comparison of measurements at specific and non-specific wavelengths dual wavelength spectrometry G01J3/427
• CPC Class Codes: G01N 21/4738 Diffuse reflection precedence is given to G01N21/55 - G01N21/57 if specular component is taken into consideration, e.g. also for testing fluids, fibrous materials
• 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 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72
• CPC Class Codes: G01N 33/521 Single-layer analytical elements
• 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
• CPC Class Codes: G01N 35/1016 Control of the volume dispensed or introduced
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

A method for determining the presence of an analyte in a fluid is described along with various components of an apparatus specifically designed to carry out the method. The method involves taking a reflectance reading from one surface of an inert porous matrix impregnated with a reagent that will interact with the analyte to produce a light-absorbing reaction product when the fluid being analyzed is applied to another surface and migrates through the matrix to the surface being read. Reflectance measurements are made at two separate wavelengths in order to eliminate interferences, and a timing circuit is triggered by an initial decrease in reflectance by the wetting of the surface whose reflectance is being measured by the fluid which passes through the inert matrix. The method and apparatus are particularly suitable for the measurement of glucose levels in blood without requiring separation of red blood cells from serum or plasma.

Claims

1. In a method for determining glucose in a blood sample, employing a membrane and a signal-producing system that produces a light-absorptive dye product, said system being bound to the membrane, in which the amount of said dye product is determined by means of a reflectance measurement from a surface of said membrane, an improvement which comprises:

applying whole blood to a surface of said membrane, and making said measurement on a surface of said membrance other than the surface to which said sample is applied.

2. A method according to claim 1, wherein said signal-producing system produces a dye product which absorbs light at a wavelength different from the wavelength at which said red blood cells absorb and said reflectance measurement is made at two different wave lengths, one at the absorption wavelength of the red blood cells and one at the absorption wavelength of said dye product.

3. A method according to claim 2, wherein said two wavelengths are at about 635 and 700 nm.

4. A method according to claim 1, wherein said signal producing system comprises glucose oxidase, peroxidase and MBTH-DMAB indicator.

5. A method according to claim 1, wherein the surface of said membrance is a polyamide.

6. A method according to claim 5, wherein said polyamide is positively charged and glucose oxidase, peroxidase and MBTH-DMAB indicator are bound to said membrance prior to use in said method.

7. A method for determining glucose comprising the steps of:

applying a whole blood sample to a reagent element, wherein said reagent element comprises a hydrophilic matrix to which is bound glucose oxidase, peroxidase, and a dye indicator capable of forming a reaction product;

allowing the sample to penetrate said membrane;

initiating timing of a predetermined timed reflectance readings by detecting penetration of the sample through said membrane; and

by a decrease in reflectance; and

determining the amount of glucose in said sample by the additional change in reflectance resulting from absorbance by said dye product.

8. A method according to claim 7, wherein said dye indicator is MBTH-DMAB indicator.

9. A method according to claim 7, wherein said hydrophilic memberane has a polyamide surface.

10. A method according to claim 9, wherein said hydrophilic membrane is positively charged.

11. A method of initiating timing of a measurement in a reflectance-reading device, which comprises:

taking at least one first reflectance reading from a first surface of porous matrix prior to application of a sample to a second surface of said matrix;

taking at least one additional reflectance reading from said first surface;

comparing said additional reflectance reading to said first reflectance reading and initiating time measurement upon a predetermined drop in reflectance resulting from said sample reaching said first surface; and

taking at least one measurement reflectance reading at a predetermined time after said additional reflectance reading differs from said reflectance value by said predetermined difference.

12. A method according to claim 11, wherein said surface is initially dry and said additional reflectance reading differs from said first reflectance value when a liquid assay medium penetrates to said first surface of said matrix.

13. A method according to claim 12, wherein said matrix has a dye precursor bound to the matrix.

14. A measuring apparatus for the determination of an analyte in a fluid, which comprises:

a container having a light-tight closure adapted to removably contain a porous matrix capable of containing an absorbed fluid to be analyzed;

means for illuminating a surface of said matrix;

means for detecting light of two different wavelengths reflected from said matrix;

control means for collecting readings of reflected light and calculating a value for the amount of analyte in said fluid based on readings of analyte or reaction product absorbance from the first wavelength of reflected light and of background absorbance from the second wavelength of reflected light; and

means for reporting said value.

15. The apparatus of claim 14, wherein said apparatus further comprises a self-contained electronic power supply operationally connected to said means for illuminating, means for detecting, control means, and reporting means.

16. The apparatus of claim 14, wherein said means for illuminating and means for detecting light of two different wavelengths together comprise:

1) two light sources of different wavelengths and a single light detector;

or

     2) a polychromic light source and two detectors restricted to detecting different wavelengths of light.

17. The apparatus of claim 14, wherein the first wavelength of light is from 690 to 710 nm and the second wavelength of light is from 625 to 645 nm.

18. The apparatus of claim 14, wherein said control means causes a timing circuit to be initiated based on initial decrease in reflectance of either wavelength of light, said decrease occuring when said fluid penetrates said matrix after being applied to said matrix on a surface other than the surface illuminated by said illuminating means.

19. The apparatus of claim 14, wherein said control means causes one or more readings of reflected light to be taken at predetermined intervals after said initial decrease in reflectance.

20. The apparatus of claim 19, wherein said control means is capable of collecting and storing a reading of reflectance from said reagent pad prior to application of fluid to said reagent pad.

21. The apparatus of claim 20, wherein said control means is further capable of collecting and storing a background detector current reading in the absence of light reflected from said reagent pad.

22. The apparatus of claim 21, wherein when power is supplied to said control means in an analyte detection mode, said control means automatically collects and compares sequential reflectance readings from said detector, initiates a timing circuit upon detection of a drop in reflectance, collects reaction reflectance readings at predetermined intervals after said drop in reflectance, calculates a value for the concentration of analyte in said fluid being analyzed from said reaction reflectance readings, and transfers said value to said reporting means.

23. The apparatus of claim 20, wherein when power is supplied to said control means in a base reflectance mode prior to said analyte detection mode, said control means collects and stores a base reflectance reading from said matrix prior to application of fluid to said matrix and wherein when power is next supplied to said control means in the analyte detection mode, said base reflectance reading is subtracted from said reaction reflectance readings by said control means prior to calculation by said control means of said value.

24. A method of determining analyte concentration in a liquid, which comprises:

quantitatively measuring base reflectance from a first surface of a reagent element comprising an inert porous matrix and a reagent system capable of interacting with said analyte to produce a light-absorbing reaction product, said reagent system being impregnated in the pores of said matrix, prior to application of said liquid to said reagent element;

quantitatively measuring reaction reflectance from said reagent element after application of said liquid to a second surface of said reagent element other than the first surface from which said reaction reflectance is measured and after said liquid has migrated through said reagent element from said second surface to said first surface;

quantitatively measuring interference reflectance from said first surface of said reagent element after said application of liquid using a wavelength of light different from the wavelength of light used to measure said reaction reflectance; and

calculating a value expressing said concentration from said reflectance measurements.

25. The method of claim 24, wherein said matrix has surfaces formed from a polyamide.

26. The method of claim 24, wherein the average diameter of the pores in said matrix is from 0.2 to 1.0 m and said liquid is whole blood.

27. The method of claim 26, wherein said reagent produces a light-absorbing reaction product upon reacting with glucose.