Analyte detection systems

• US 6,121,050 A
• Filed: 08/29/1997
• Issued: 09/19/2000
• Est. Priority Date: 08/29/1997
• Status: Expired due to Fees

• Current Assignee: Chi-Neng Arthur Han
• Original Assignee: Chi-Neng Arthur Han
• Inventors: Han, Chi-Neng Arthur
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US08/920,822
• Time in Patent Office: 1,117 Days
• Field of Search: 436/46, 436/93-95, 436/164, 436/166, 436/169, 436/172, 422/56, 422/82.05, 422/82.08, 422/82.09
• US Class Current: 436/95
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• 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 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

The present invention is directed to an improved analyte systems which are able to compensate for interfering signals and to provide accurate detection and/or quantification of analytes in a sample. In particular, the invention describes new methods, systems, and devices for indirectly determining the presence of one or more analytes in a multi-component medium.

Claims

1. An analyte detection system for determining the presence and/or concentration of glucose in a blood sample having two or more interfering components masking the presence and/or concentration of glucose in contact with a substrate having a blood application surface and an analyte detection surface wherein the presence and/or concentration of glucose cannot be directly determined comprising:

a) means for introducing said blood sample onto said blood application surface;

b) means for allowing said sample to migrate through said porous substrate to said analyte detection surface, wherein said detection surface includes a glucose-specific reagent and an indicator disposed thereon;

c) means for forming a signal producing composition through the reaction of said glucose-specific reagent, said indicator and said glucose present in said blood sample;

d) means for stimulating said sample with one or more stimuli;

e) means for detecting one or more signals produced in response to d, and for correcting for any interfering signals produced by other analytes and/or two or more interfering components, wherein the number of stimuli required is equal to or greater than the sum of the number of analytes in said sample and any interfering components therein, provided that said stimuli for said interfering components are different from a stimulus for measuring said glucose and the interfering components must not simultaneously overlap at at least one correction point and further provided that said signal producing composition produces a measurable response having a characteristic ratio of signals at two different stimuli; and

f) means for determining the presence and/or concentration of said glucose by applying a mathematical formula to said one or more signals.

2. The system of claim 1, wherein said porous substrate further comprises a matrix of a hydrophilic polymer, said polymer having pores dispersed throughout said matrix and in communication with said blood application and analyte detection surfaces, wherein the diameter of said pores is sufficiently large to allow at least a portion of said sample to freely migrate therebetween.

3. The system according to claim 1, wherein the presence of glucose in said blood sample is detected with a percent coefficient of variance between about 30% to about 50%.

4. The system according to claim 1, wherein the concentration of glucose in said blood sample is detected with a percent coefficient of variance of about 3% to about 7%.

5. The system according to claim 1, wherein said one or more signals are detected by exciting said blood sample at at least three excitation wavelengths and measuring its absorbance produced at said at least three wavelengths λ

_a, λ

_b and λ

_c, respectively.

6. The system according to claim 5, wherein said presence and/or concentration of glucose is proportional to the magnitude of a signal produced by said glucose (Aa) and is determined according to mathematical formula I:

space="preserve" listing-type="equation">Concentration and/or Presence of Glucose=E·

Aa

wherein Aa=(Aa'"'"'-kb·

Bb'"'"'-kc·

Cc'"'"')/(1-kb·

kd-kc·

ke) and Aa is said true value for said analyte, Aa'"'"' is a measurable signal produced at λ

_a in response to a single stimulus by said signal producing composition (Aa) and said no more than two interfering components (Ba and Ca) Bb'"'"' is a measurable signal produced at λ

_b in response to said stimulus by said signal producing composition (Ab) and said no more than one interfering component (Bb), Cc'"'"' is a measurable signal produced at λ

_c in response to said stimulus by said signal producing composition (Ac) and said no more than one interfering component (Cc), kb is a constant and is a ratio between Ba and Bb, kc is a constant and is a ratio between Ca and Cc, kd is a constant and is a ratio between Ab and Aa, and ke is a constant and is a ratio between Ac and Aa.

7. The system according to claim 5, wherein λ

_a is about 630 nm and λ

_b is about 700 nm.

8. The system according to claim 1, wherein said signal producing composition produces a signal selected from the group consisting of absorbance, voltage, radioactivity, temperature, current, fluorescence and mixtures thereof.

9. The system according claim 1, wherein said glucose-specific reagent includes a chromogen.

10. The system according to claim 9, wherein said chromogen is 3,3'"'"',5,5'"'"'-Tetramethylbenzidine.

11. The system according to claim 1, wherein said glucose-specific reagent is a Trinder reagent.

12. A process for detecting one or more analytes in a multi-component system wherein the ability to directly detect said one or more analytes in a signal producing composition is masked by two or more interfering components of said multi-component system comprising:

a) exciting said system with one or more stimuli to produce an interference-correction signal from said signal producing composition, whereby the number of stimuli provided is equal to or greater than the sum of the number of said analytes in said multi-component medium and any interfering components therein, provided that said stimuli for said interfering components are different from a stimulus for measuring said analyte, and the interfering components must not overlap at least one interfering correction stimulus that is used for said corrections;

b) measuring said signal or signals at detection points; and

c) determining the presence and/or concentration of said one or more analytes by applying a correction to said signal or signals, wherein said signal or signals are proportional to said analyte or analytes to be detected said correction being;

space="preserve" listing-type="equation">Concentration and/or Presence of Analyte=E·

Aa

wherein Aa=(Aa'"'"'-kb·

Bb'"'"'-kc·

Cc'"'"')/(1-kb·

kd-kc·

ke) and Aa is said true value for said analyte, Aa'"'"' is a measurable signal produced in response to a single stimulus by said signal producing composition (Aa) and said no more than two interfering components (Ba and Ca) at said first detection point, Bb'"'"' is a measurable signal produced in response to said stimulus by said signal producing composition (Ab) and said no more than one interfering component (Bb) at said second detection point, Cc'"'"' is a measurable signal produced in response to said stimulus by said signal producing composition (Ac) and said no more than one interfering component (Cc) at said third detection point, kb is a constant and is a ratio between Ba and Bb, kc is a constant and is a ratio between Ca and Cc, kd is a constant and is a ratio between Ab and Aa, and ke is a constant and is a ratio between Ac and Aa.

13. The process of claim 12 further including a step of forming said signal producing composition by reacting an analyte with a reagent.

14. The process according to claim 13 wherein said analyte'"'"'s presence is detected with a percent coefficient of variance between about 30% to about 50%.

15. The process according to claim 12 wherein said analyte'"'"'s concentration is detected with a percent coefficient of variance of about 3% to about 7%.

16. The process according to claim 12, wherein said signal producing composition produces a measurable response having a characteristic ratio of signals at two different stimuli.

17. The process according to claim 12 wherein said signal producing composition produces a signal selected from the group consisting of absorbance, voltage, radioactivity, temperature, current and fluorescence.

18. The process according claim 12, wherein said analyte is glucose and said reagent is a glucose-specific reagent.

19. The process according to claim 18, wherein said glucose-specific reagent is a chromogen.

20. The process according to claim 19, wherein said chromogen is 3,3'"'"',5,5'"'"'-Tetramethylbenzidine.

21. The process according to claim 12, wherein said signal producing composition is a Trinder reagent.

22. A device for detecting the presence and/or concentration of one or more analytes in a blood sample when said analyte cannot be directly detected comprising:

a) a hydrophilic porous substrate with a blood application surface and an analyte detection surface, said substrate comprising a polymeric matrix having pores dispersed throughout said matrix and in communication with said blood application and analyte detection surfaces, wherein the diameter of said pores is sufficiently large to allow at least a portion of said sample to freely migrate therebetween;

b) an analyte-specific reagent and an indicator dispersed on said analyte detection surface for reacting with said analyte to produce a signal producing composition which, when excited, produces at least three signals at wavelengths (λ

_a), (λ

_b) and (λ

_c), respectively to correct for any interfering signal or signals produced by other analytes or interfering components in said sample;

c) excitation means for exciting said sample on said analyte detection surface;

d) detection means for detecting said at least three signals, whereby the number of signals produced must be equal to or greater than the sum of the number of said analytes in said blood sample and any interfering components therein, provided that said signals for said interfering compounds are different from a signal for measuring said analyte, and the interfering components must not overlap at at least one interfering correction stimulus that is used for said corrections and further provided that said signal producing composition produces a measurable response having a characteristic ratio of signals at the two different wavelengths;

e) means for determining the presence and/or concentration of said analyte by applying said corrections to said at least first and second signals, said corrections being;

space="preserve" listing-type="equation">Concentration and/or Presence of Glucose=E·

Aa

wherein Aa=(Aa'"'"'-kb·

Bb'"'"'-kc·

Cc'"'"')/(1-kb·

kd-kc·

ke) and Aa is said true value for said analyte, Aa'"'"' is a measurable signal produced λ

_a, in response to a single stimulus by said signal producing composition (Aa) and said no more than two interfering components (Ba and Ca), Bb'"'"' is a measurable signal produced at λ

_b in response to said stimulus by said signal producing composition (Ab) and said no more than one interfering component (Bb), Cc'"'"' is a measurable signal produced at λ

_c in response to said stimulus by said signal producing composition (Ac) and said no more than one interfering component (Cc), kb is a constant and is a ratio between Ba and Bb, kc is a constant and is a ratio between Ca and Cc, kd is a constant and is a ratio between Ab and Aa, and ke is a constant and is a ratio between Ac and Aa and;

f) display means for displaying said presence and/or concentration of said analyte.

23. A method for determining the presence and/or concentration of glucose in a blood sample in contact with a porous substrate having a blood application surface and an analyte detection surface wherein the presence and/or concentration of glucose cannot be directly determined comprising:

a) introducing said blood sample onto said blood application surface;

b) allowing a portion of said sample to migrate through said porous substrate to said analyte detection surface, wherein said detection surface includes a glucose-specific reagent and an indicator disposed thereon;

c) forming a signal producing composition through the reaction of said glucose-specific reagent, said indicator and said glucose present in said blood sample;

d) stimulating said sample with one or more stimuli;

e) detecting one or more signals produced in response to d, and for correcting for at least two or more interfering signals produced by other analytes and/or interfering components, wherein the number of stimuli required is equal to or greater than the sum of the number of analytes in said sample and any interfering components therein, provided that said stimuli for said interfering compounds are different from a stimulus for measuring said glucose and the interfering components must not overlap at at least one interfering correction stimulus that is used for said corrections and further provided that said signal producing composition produces a measurable response having a characteristic ratio of signals at two different stimuli; and

f) determining the presence and/or concentration of said glucose by applying said corrections based on said characteristic ratio to said one or more signals.

24. The method of claim 23, wherein said porous substrate further comprises a matrix of a hydrophilic polymer, said polymer having pores dispersed throughout said matrix and in communication with said blood application and analyte detection surfaces, wherein the diameter of said pores is sufficiently large to said portion of said blood sample to freely migrate therebetween.

25. The method according to claim 24, wherein the presence of glucose in said blood sample is detected with a percent coefficient of variance between about 30% to about 50%.

26. The method according to claim 24, wherein the concentration of glucose in said blood sample is detected with a percent coefficient of variance of about 3% to about 7%.

27. The method according to claim 24, wherein said one or more signals are detected by exciting said blood sample at least two excitation wavelengths and measuring its absorbance produced at said at least three wavelengths λ

_a, λ

_b and λ

_c, respectively.

28. The method according to claim 27, wherein said presence and/or concentration of glucose is proportional to the magnitude of a signal produced by said glucose (Aa) and is determined according to mathematical formula I:

space="preserve" listing-type="equation">Concentration and/or Presence of Glucose=E·

Aa

wherein Aa=(Aa'"'"'-kb·

Bb'"'"'-kc·

Cc'"'"')/(1-kb·

kd-kc·

ke) and Aa is said true value for said analyte, Aa'"'"' is a measurable signal produced at λ

_a, in response to a single stimulus by said signal producing composition (Aa) and said no more than two interfering components (Ba and Ca) Bb'"'"' is a measurable signal produced at λ

_b in response to said stimulus by said signal producing composition (Ab) and said no more than one interfering component (Bb), Cc'"'"' is a measurable signal produced at λ

_c in response to said stimulus by said signal producing composition (Ac) and said no more than one interfering component (Cc), kb is a constant and is a ratio between Ba and Bb, kc is a constant and is a ratio between Ca and Cc, kd is a constant and is a ratio between Ab and Aa, and ke is a constant and is a ratio between Ac and Aa.

29. The method according to claim 27, wherein λ

_a is about 630 nm and λ

_b is about 700 nm.

30. The method according to claim 24, wherein said signal producing composition produces a signal selected from the group consisting of absorbance, voltage, radioactivity, temperature, current, fluorescence and mixtures thereof.

31. The method according to claim 24, wherein said glucose-specific reagent includes a chromogen.

32. The method according to claim 31, wherein said chromogen is 3,3'"'"',5,5'"'"'-Tetramethylbenzidine.

33. The method according to claim 24, wherein said glucose-specific reagent is a Tinder reagent.