Precursor indicator compositions

• US 4,307,188 A
• Filed: 09/06/1979
• Issued: 12/22/1981
• Est. Priority Date: 09/06/1979
• Status: Expired due to Term

• Current Assignee: Miles Laboratories, Inc. (Bayer AG)
• Original Assignee: Miles Laboratories, Inc. (Bayer AG)
• Inventors: White, William I.
• Primary Examiner(s): Wiseman, Thomas G.
• Application Number:
  US06/073,098
• Time in Patent Office: 838 Days
• Field of Search: 435/4, 435/15, 435/18, 435/19, 435/17, 435/16, 435/20, 435/21, 435/23, 435/24, 435/25, 435/28, 435/805, 435/810, 424/2, 23/230 B, 23/230 R
• US Class Current: 435/4
• CPC Class Codes: C12Q 1/28 involving peroxidase
• CPC Class Codes: C12Q 1/34 involving hydrolase
• CPC Class Codes: C12Q 1/42 involving phosphatase
• CPC Class Codes: C12Q 1/44 involving esterase
• CPC Class Codes: C12Q 1/46 involving cholinesterase
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: C12Q 1/61 involving triglycerides
• CPC Class Codes: C12Q 2326/32 3-Methyl-2-benzothiazolinone hydrazone hydrochloride hydrate, i.e. MBTH
• CPC Class Codes: C12Q 2334/30 Naphthol derivatives, e.g. alpha-naphthyl-esters, i.e. alpha-NE, beta-naphthyl-esters, i.e. beta-NE
• CPC Class Codes: C12Q 2334/50 Indoles
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• 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: Y10S 435/805 Test papers
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

A composition, test device, method of making a test device and process for determination of an analyte in a liquid sample are disclosed. More particularly, there is provided a composition for detecting an analyte in a liquid sample comprising an analyte-responsive component and an indicator composition having a plurality of components comprising at least one nonresponsive precursor component and at least one component effective in a liquid milieu to alter said precursor component so as to release at least one substance effective to permit said indicator composition, in combination with said analyte-responsive component, to produce a detectable response to said analyte. The composition can optionally be incorporated with a carrier to form a device.

Claims

1. A composition for detecting an analyte in a liquid sample comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage and (2) a hydrolytic catalyst in an amount effective in a liquid milieu to cleave the ester or amide linkage so as to release a substance effective to permit said indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte.

2. The composition of claim 1 wherein the nonresponsive precursor component is indoxyl acetate and the component effective to alter said nonresponsive precursor component is a catalyst capable of cleaving the acetate group from the indoxyl acetate.

3. The composition of claim 2 wherein the component effective to alter said nonresponsive precursor component is cholinesterase.

4. The composition of claim 2 wherein the component effective to alter said nonresponsive precursor component is imidazole.

5. The composition of claim 1 wherein the nonresponsive precursor component is a compound having the structure ##STR8## in which Y is lower alkyl carbonyl, lower alkoxy carbonyl or a phosphate ester of the structure ##STR9## in which R and R'"'"' are independently H or lower alkyl, and, each X is independently selected from bromine and chlorine.

6. The composition of claim 5 wherein the component effective to alter said nonresponsive precursor component is an esterase when Y is alkyl carbonyl, a carbonic anhydrase when Y is lower alkoxy carbonyl or a phosphatase when Y is phosphate ester.

7. The composition of claim 1 wherein the nonresponsive precursor component is a compound having the structure ##STR10## in which R is independently hydrogen or lower alkyl.

8. The composition of claim 7 wherein the component effective to alter said nonresponsive precursor component is β

-glucuronidase.

9. The composition of claim 1 wherein the indicator comprises a component resulting from the alteration of the precursor component and an interreactive coupling compound selected from the group consisting of 3-loweralkykl-2-benzothiazolinone hydrazone and 1-loweralkyl-2-quinolinonehydrazone.

10. The composition of claim 9 wherein the nonresponsive precursor component is (γ

-glutamyl)-1-naphthylamine.

11. The composition of claim 10 wherein the component effective to alter said nonresponsive precursor component is γ

-glutamyl transferase.

12. The composition of claim 9 wherein the nonresponsive precursor component is a lower peptide ester having the structure ##STR11## in which R and R'"'"' are independently hydrogen, alkyl, alkoxy, halogen, or together form an aromatic hydrocarbon ring.

13. The composition of claim 12 wherein the component effective to alter said nonresponsive precursor component is an esterase.

14. The composition of claim 9 wherein the nonresponsive precursor component is a component having the structure ##STR12## wherein R and R'"'"' are independently H or lower alkyl.

15. The composition of claim 14 wherein the component effective to alter said nonresponsive precursor component is a phosphatase.

16. The composition of claim 9 wherein the nonresponsive precursor component is a compound having the structure ##STR13## wherein R is H, lower alkyl, or lower alkoxy.

17. The composition of claim 16 wherein the component effective to alter said nonresponsive precursor component is β

-glucosidase.

18. The composition of claim 9 wherein the nonresponsive precursor component is a compound having the structure ##STR14## wherein R is H or lower alkyl.

19. The composition of claim 18 wherein the component effective to alter said nonresponsive precursor component is β

-glucuronidase.

20. A device for detecting a sample analyte which comprises a carrier, which carrier is insoluble in and maintains its structural integrity when exposed to the sample to be tested, incorporated with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage and (2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte.

21. A device for detecting a sample analyte which comprises a carrier, which carrier is insoluble in and maintains its structural integrity when exposed to the sample to be tested, incorporated with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage;

(2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte;

(3) a component resulting from the alteration of the precursor component; and

(4) a coupling compound, which is interreactive with the component resulting from the alteration of the precursor component and selected from the group consisting of 3-loweralkyl-2-benzothiazolinone hydrazone and 1-loweralkyl-2-quinolinone hydrazone.

22. A process for preparing a device for detecting a sample analyte which comprises the steps of:

(a) incorporating a carrier, which carrier is insoluble in and maintains its structural integrity when exposed to the sample to be tested, with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage;

(2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte; and

thereafter

(b) drying the carrier which has been so incorporated.

23. A process for preparing a device for detecting a sample analyte which comprises the steps of:

(a) incorporating a carrier, which carrier is insoluble in and maintains its structural integrity when exposed to the sample to be tested, with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage;

(2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte;

(3) a component resulting from the alteration of the precursor component; and

(4) a coupling compound, which is interreactive with the component resulting from the alteration of the precursor component and selected from the group consisting of 3-loweralkyl-2-benzothiazolinone hydrazone and 1-loweralkyl-2-quinolinone hydrazone; and

thereafter

(b) drying the carrier which has been so incorporated.

24. A method for detecting an analyte in a sample which comprises the steps of:

(a) contacting the sample with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage and (2) a component effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte; and

thereafter

(b) observing any detectable response.

25. A method for detecting an analyte in a sample which comprises the steps of:

(a) contacting the sample with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage and (2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte;

(3) a component resulting from the alteration of the precursor component; and

(4) a coupling compound, which is interreactive with the component resulting from the alteration of the precursor component and selected from the group consisting of 3-loweralkyl-2-benzothiazolinone hydrazone and 1-loweralkyl-2-quinolinone hydrazone; and

thereafter

(b) observing any detectable response.

26. A method for detecting an analyte in a sample which comprises the steps of:

(a) contacting the sample with a device which comprises a carrier, which carrier is insoluble in and maintains its structural integrity when exposed to the sample to be tested, incorporated with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage and (2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte; and

thereafter

(b) observing any detectable response.

27. A method for detecting an analyte in a sample which comprises the steps of:

(a) contacting the sample with a device which comprises a carrier, which carrier is insoluble in and maintains its structural integrity when exposed to the sample to be tested, incorporated with a composition comprising an analyte-responsive component and an indicator composition comprising (1) a nonresponsive precursor component having an ester or amide linkage;

(2) a hydrolytic catalyst in an amount effective in a liquid milieu to alter the nonresponsive precursor component so as to release a substance effective to permit the indicator composition, through reaction with a product of the analyte-responsive component, to produce a detectable response to the analyte;

(3) a component resulting from the alteration of the precursor component; and

(4) a coupling compound, which is interreactive with the component resulting from the alteration of the precursor component and selected from the group consisting of 3-loweralkyl-2-benzothiazolinone hydrazone and 1-loweralkyl-2-quinolinone hydrazone; and

thereafter

(b) observing any detectable response.