Methods and kits for assays of analytes of interest in tears

• US 20040076547A1
• Filed: 09/03/2003
• Published: 04/22/2004
• Est. Priority Date: 10/03/2002
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Lane, Jennifer Dawn, Carney, Fiona Patricia, Morris, Carol Ann
• Granted Patent: US 7,244,394 B2
• Time in Patent Office: Days
• US Class Current: 422/82.08
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/0067 Tear or lachrymal fluid

Abstract

The invention, in one aspect, provides a strip for tear collection. The strip has a first end and an opposite second end and preferably has substantially uniform cross-sections from the first end to the second end. The strip is made of a hydrogel material in substantially dry state. The strip is characterized by having a substantially uniform swelling along the hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by said strip and the length of the wicked end portion of said strip. A strip of the invention is useful for assay of an analyte of interest in a tear fluid. The invention also provides a method and kits for assaying an analyte of interest (e.g., lactoferrin, glucose, herpes simplex virus, hormones, etc.).

Claims

1. A strip for tear collection, having a first end and an opposite second end, wherein said strip is made of a hydrogel material in substantially dry state, wherein said strip is characterized by having a substantially uniform swelling along the hydrogel strip from the first end to the second end when fully wicked by the tear fluid and characterized by having a defined correlation between the volume of tear uptake by said strip and the length of the tear-wicked end portion of said strip.

2. A strip of claim 1, wherein said strip has substantially uniform cross-sections from the first end to the second end.

3. A strip of claim 1, wherein said hydrogel material is selected from the group consisting of poly(vinyl alcohol), modified polyvinylalcohol, poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(vinyl alcohol) with polycarboxylic acids, polyethylene glycol, polyacrylamide, polymethacrylamide, silicone-containing hydrogels, polyurethane, polyurea, and mixtures thereof.

4. A strip of claim 2, wherein the cross-section of said strip has a rectangular shape.

5. A strip of claim 4, wherein the cross-section of said strip has a width of from about 1 mm to about 3 mm and a height of from 0.5 mm to 1.5 mm.

6. A strip of claim 4, wherein the cross-section of said strip has a width of from 1.5 mm to 2 mm and a height of from 0.8 mm to 1.2 mm.

7. A strip of claim 2, wherein the cross-section of said strip is circular, and wherein the diameter of the circular cross-section is from 1 mm to 3 mm.

8. A strip of claim 1, wherein said defined correlation between the volume of tear uptake by said strip and the length of the tear-wicked end portion of said strip is a substantially linear relationship.

9. A strip of claim 1, wherein said strip has noticeable marks thereon, wherein each of the marks indicates a volume of the tear fluid absorbed by the end portion up to that mark of said strip.

10. A method for assaying an analyte of interest in a tear fluid of an eye, comprising the steps of:

placing an end portion of a strip at a location in the eye away from the cornea of the eye to wick (absorb) an amount of the tear fluid, wherein said strip is made of a hydrogel material in substantially dry state and preferably has substantially uniform cross-sections from one end to the other end, wherein said strip is characterized by having a substantially uniform swelling along the hydrogel strip from one end to the other end when fully wicked by the tear fluid and by having a defined correlation between the volume of tear uptake by said strip and the length of the tear-wicked end portion of said strip;

separating a fraction or all of the tear-wicked end portion of said strip from the rest portion;

determining the presence or the amount of the analyte of interest using the fraction or all of the tear-wicked end portion of said strip.

11. A method of claim 10, wherein the cross-section of said strip is rectangular and has has a width of from about 1 mm to about 3 mm and a height of from 0.5 mm to 1.5 mm.

12. A method of claim 10, wherein said strip is placed at a location near the lateral canthus of an eye to collect tear fluids.

13. A method of claim 10, wherein the cross-section of said strip is circular, and wherein the diameter of the circular cross-section is from 1 mm to 3 mm.

14. A method of claim 10, wherein said analyte of interest is selected from the group consisting of an electrolyte, a metallic element, a polypeptide hormone, a chronically administered medication, an acutely administered medication, a small molecule hormone, a marker of inflammation, a marker of allergy, a lipid, a protein, a marker of infection, and a metabolite.

15. A method of claim 14, wherein said analyte of interest is lactoferrin.

16. A method of claim 14, wherein said analyte of interest is glucose.

17. A kit for assaying an analyte of interest in a tear fluid of an eye, comprising:

a strip for collecting the tear fluid, wherein said strip has a first end and an opposite second end, wherein said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along the hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by said strip and the length of a tear-wicked end portion of said strip; and

a testing agent composition which specifically reacts with the analyte of interest to form a detectable signal.

18. A kit of claim 17, wherein the cross-section of said strip is circular, and wherein the diameter of the circular cross-section is from 1 mm to 3 mm.

19. A kit of claim 17, wherein the cross-section of said strip is rectangular and has a width of from about 1 mm to about 3 mm and a height of from 0.5 mm to 1.5 mm.

20. A kit of claim 17, wherein said hydrogel material is selected from the group consisting of poly(vinyl alcohol), modified polyvinylalcohol, poly(hydroxyethyl methacrylate), poly(vinyl pyrrolidone), poly(vinyl alcohol) with polycarboxylic acids, polyethylene glycol, polyacrylamide, polymethacrylamide, silicone-containing hydrogels, polyurethane, polyurea, and mixtures thereof.

21. A kit of claim 17, wherein said defined correlation between the volume of tear uptake by said strip and the length of the tear-wicked end portion of said strip is a substantially linear relationship.

22. A kit of claim 17, wherein said strip has noticeable marks thereon, wherein each of the marks indicates a volume of the tear fluid absorbed by the end portion up to that mark of said strip.

23. A kit of claim 17, wherein said analyte of interest is selected from the group consisting of:

an electrolyte, a metallic element, a polypeptide hormone, a chronically administered medication, an acutely administered medication, a small molecule hormone, a marker of inflammation, a marker of allergy, a lipid, a protein, a marker of infection, and a metabolite.

24. A kit of claim 23, wherein said analyte of interest is lactoferrin.

25. A kit of claim 23, wherein said analyte of interest is glucose.

26. A kit of claim 17, wherein said testing agent composition comprises a receptor that is capable of binding reversibly said analyte of interest and has a detectable optical signal that changes in a concentration-dependent manner when the receptor is bound to said analyte, wherein said detectable optical signal results from one or more labels associated with the receptor.

27. A kit of claim 26, wherein said detectable spectral change is selected from the group consisting of changes in fluorescent decay time, fluorescent intensity, fluorescent anisotropy, fluorescence polarization, a spectral shift of the emission spectrum, and a change in time-resolved anisotropy decay.

28. A kit of claim 26, wherein the testing agent composition comprises:

(1) a fluorescent energy donor and a fluorescent energy acceptor;

or (2) a fluorescent energy donor and a non-fluorescent energy acceptor.

29. A kit of claim 17, wherein the testing agent composition comprises a receptor having a first label associated therewith, a competitor having a second label associated therewith, wherein one of the first and second labels is a fluorescent energy donnor and the other one is a fluorescent or non-fluorescent energy acceptor said testing agent composition comprises a receptor and a competitor, wherein said receptor comprises a analyte/competitor binding site to which the analyte can be reversibly bound.

30. A kit of claim 26, wherein the testing agent composition is one or more solutions or is incorporated partially or fully in said strip.

31. A kit of claim 29, wherein the testing agent composition is one or more solutions or is incorporated partially or fully in said strip.