Diagnostic assay device

• US 20060121626A1
• Filed: 12/03/2004
• Published: 06/08/2006
• Est. Priority Date: 12/03/2004
• Status: Active Grant

• Current Assignee: Sekisui Diagnostics, LLC (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Imrich, Michael Reece
• Granted Patent: US 7,465,587 B2
• Time in Patent Office: Days
• US Class Current: 436/514
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: Y10S 435/961 including a step of forming, releasing, or exposing the antigen or forming the hapten-immunogenic carrier complex or the antigen per se
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick
• CPC Class Codes: Y10S 436/824 Immunological separation techniques
• CPC Class Codes: Y10S 436/825 Pretreatment for removal of interfering factors from sample

Abstract

This invention relates to assays for an analyte in a liquid sample such as a body fluid. More particularly, the invention relates to a method and apparatus for the detection of a ligand in a body fluid such as urine or blood, which includes an immobilization zone for interfering agents in a sample.

Claims

1. An assay device for detection of the presence or absence of an analyte in a sample comprising:

(a) a sample receiving membrane which conducts flow of a sample, and in flow contact with,

(b) an analyte detection membrane which conducts flow of the sample comprising an interfering agent immobilization zone at a first situs, a conjugate forming membrane comprising a mobile labeling reagent at a labeling situs, and an immobile capture reagent at a capture situs, wherein the labeling reagent is capable of forming a complex with an analyte, the capture reagent is capable of binding an analyte-labeling reagent complex, and the interfering agent immobilization zone is capable of binding an interfering agent in the sample.

2. The assay device of claim 1, wherein the flow contact between the sample receiving membrane and analyte detection membrane is lateral flow contact.

3. The assay device of claim 1, wherein the interfering agent immobilization zone is an IgG antibody, an IgM antibody, or a portion thereof.

4. The assay device of claim 3, wherein the antibody or portion thereof is mouse, goat, sheep, rat, rabbit, or cow.

5. The assay device of claim 1, wherein the first situs is located between the sample receiving membrane and the mobile labeling situs.

6. The assay device of claim 1, wherein the first situs is located between the capture reagent and the labeling situs.

7. The assay device of claim 1, wherein the first situs is located in the sample receiving membrane.

8. The assay device of claim 1, wherein the first situs is located between the sample receiving membrane and the mobile labeling situs.

9. The assay device of claim 1, wherein the first situs is located between the capture reagent and the sample receiving membrane.

10. The assay device of claim 1, wherein the interfering agent is immobilized at the interfering agent immobilization zone.

11. The assay device of claim 1, wherein the back of the sample receiving membrane and the analyte detection membrane are laminated with a semi-rigid material.

12. The assay device of claim 1, wherein the sample is blood, serum, nasal fluid, urine, sweat, plasma, semen, cerebrospinal fluid, tears, pus, amniotic fluid, saliva, lung aspirate, gastrointestinal contents, vaginal discharge, urethral discharge, chorionic villi specimens, skin epithelials, genitalia epithelials, gum epithelials, throat epithelials, hair, or sputum.

13. The assay device of claim 1, wherein the sample receiving membrane and the analyte detection membrane are enclosed in a housing.

14. The assay device of claim 13, wherein the housing comprises a sample application aperture and an observation window positioned to display the immobile capture situs and control situs.

15. The assay device of claim 1, further comprising an absorbent sink in lateral flow contact with the analyte detection membrane.

16. The assay device of claim 1, further comprising a control reagent immobilized at a control situs.

17. The assay device of claim 16, wherein the control reagent comprises an anti-mouse IgG, an anti-goat IgG, an anti-cow IgG, anti-rabbit IgG, or an anti-rat IgG.

18. The assay device of claim 16, wherein the control reagent is immobilized between the immobile capture reagent and an end of the analyte detection membrane.

19. The assay device of claim 1, wherein an accumulation of the interfering agent at the interfering agent immobilization zone does not produce a signal indicative of the presence of interfering agent in the sample.

20. The assay device of claim 1, wherein the analyte is a protein, peptide;

small molecule;

antibody, nucleic acid, viruse, virus particle, human chorionic gonadotrophin, luteinizing hormone, estrone-3-glucoronide, pregnanediol-3-glucoronide, insulin, glucagon, relaxin, thyrotropin, somatotropin, gonadotropin, follicle-stimulating hormone, gastrin, bradykinin, vasopressin, polysaccharides, estrone, estradiol, cortisol, testosterone, progesterone, chenodeoxycholic acid, digoxin, cholic acid, digitoxin, deoxycholic acid, lithocholic acids;

vitamins, thyroxine, triiodothyronine, histamine, serotorin, prostaglandin, drug, drug metabolite, ferritin, or CEA.

21. The assay device of claim 1, wherein the interfering agent is an antibody or an analyte mimic.

22. An assay device for detection of the presence or absence of an analyte in a sample comprising:

(a) a sample receiving membrane which conducts flow of a liquid sample, in flow contact with;

(b) an analyte detection membrane which conducts flow of the sample comprising an interfering agent immobilization zone at a first situs, a conjugate forming membrane comprising a mobile labeling reagent at a labeling situs, and an immobile capture reagent at a capture situs, wherein the labeling reagent is capable of forming a complex with an analyte, the capture reagent is capable of binding an analyte-labeling reagent complex, and the interfering agent immobilization zone is capable of binding an interfering agent in the sample; and

(c) an absorbent sink in flow contact with the analyte detection membrane,

wherein the sample receiving membrane, the analyte detection membrane, and the absorbent sink are enclosed in a housing, comprising a sample application aperture and an observation window positioned to display the immobile capture situs and control situs.

23. The assay device of claim 22, wherein the flow contact is lateral flow contact.

24. The assay device of claim 22, wherein the interfering agent immobilization zone is an IgG antibody or a portion thereof.

25. The assay device of claim 22, wherein the first situs is located between the sample receiving membrane and the mobile labeling situs.

26. The assay device of claim 22, wherein the first situs is located between the capture reagent and the labeling situs.

27. The assay device of claim 22, wherein the first situs is located in the sample receiving membrane.

28. The assay device of claim 22, wherein the first situs is located between the sample receiving membrane and the mobile labeling situs.

29. The assay device of claim 22, wherein the first situs is located between the capture reagent and the sample receiving membrane.

30. The assay device of claim 22, wherein the interfering agent is immobilized at the interfering agent immobilization zone.

31. The assay device of claim 22, wherein an accumulation of the interfering agent at the interfering agent immobilization zone does not produce a signal indicative of the presence of interfering agent in the sample.

32. The assay device of claim 22, further comprising a control reagent immobilized at a control situs.

33. The assay device of claim 32, wherein the control reagent is immobilized between the immobile capture reagent and an end of the analyte detection membrane.

34. The assay device of claim 22, wherein the interfering agent is an antibody or an analyte mimic.

35. An assay device for detection of the presence or absence of an analyte in a sample comprising

a membrane comprising,

a sample receiving zone which conducts lateral flow of a liquid sample, in lateral flow contact with an analyte capture situs which conducts lateral flow of the sample comprising an interfering agent immobilization zone at a first situs, a conjugate forming membrane comprising a mobile labeling reagent at a labeling situs, and an immobile capture reagent at a capture situs,

wherein the labeling reagent is capable of forming a complex with an analyte, the capture reagent is capable of binding an analyte-labeling reagent complex, and the interfering agent immobilization zone is capable of binding an interfering agent in the sample, and

a backing laminated to a bottom surface of the sample receiving membrane and the analyte detection membrane.

36. The assay device of claim 35, wherein the backing comprising semi-rigid material of at least 0.005 inches thick to produce a device with adequate mechanical strength in the absence of a plastic casing.

37. The assay device of claim 35, wherein the interfering agent at the interfering agent immobilization zone is an IgG antibody, an IgM antibody, or a portion thereof.

38. The assay device of claim 35, wherein the first situs is located between the sample receiving zone and the mobile labeling situs.

39. The assay device of claim 35, wherein the first situs is located between the capture reagent and the labeling situs.

40. The assay device of claim 35, wherein the first situs is located in the sample receiving zone.

41. The assay device of claim 35, wherein the first situs is located between the sample receiving zone and the mobile labeling situs.

42. The assay device of claim 35, wherein the first situs is located between the capture reagent and the sample receiving zone.

43. The assay device of claim 35, wherein the interfering agent is immobilized at the interfering agent immobilization zone.

44. The assay device of claim 35, wherein an accumulation of the interfering agent at the interfering agent immobilization zone does not produce a signal indicative of the presence of interfering agent in the sample.

45. The assay device of claim 35, further comprising an absorbent sink in lateral flow contact with the analyte capture situs.

46. The assay device of claim 35, wherein the interfering agent is an antibody or an analyte mimic.

47. An assay device for detection of the presence or absence of an analyte in a sample comprising

a membrane comprising,

a sample receiving zone which conducts lateral flow of a liquid sample, in lateral flow contact with an analyte capture situs which conducts lateral flow of the sample comprising an interfering agent immobilization zone at a first situs, a conjugate forming membrane comprising a mobile labeling reagent at a labeling situs, and an immobile capture reagent at a capture situs,

wherein the labeling reagent is capable of forming a complex with an analyte, the capture reagent is capable of binding an analyte-labeling reagent complex, and the interfering agent immobilization zone is capable of binding an interfering agent in the sample.

48. The assay device of claim 47, wherein the first situs is located between the sample receiving membrane and the mobile labeling situs.

49. The assay device of claim 47, wherein the first situs is located between the capture reagent and the labeling situs.

50. The assay device of claim 47, wherein the first situs is located in the sample receiving membrane.

51. The assay device of claim 47, wherein the first situs is located between the sample receiving membrane and the mobile labeling situs.

52. The assay device of claim 47, wherein the first situs is located between the capture reagent and the sample receiving membrane.

53. The assay device of claim 47, wherein the interfering agent is immobilized at the interfering agent immobilization zone.

54. The assay device of claim 47, wherein an accumulation of the interfering agent at the interfering agent immobilization zone does not produce a signal indicative of the presence of interfering agent in the sample.

55. A method of detecting the presence of an analyte in a sample, comprising:

applying a sample to an assay device;

wherein the assay device comprises a sample receiving membrane which conducts flow of a liquid sample in flow contact with an analyte detection membrane which conducts flow of the sample,

wherein the analyte detection membrane comprises a interfering agent immobilization zone at a first situs, a conjugate forming membrane comprising a mobile labeling reagent at a labeling situs, and an immobile capture reagent at a capture situs,

wherein the labeling reagent is capable of forming a complex with the analyte, the capture reagent is capable of binding the analyte-labeling reagent complex, and the interfering agent immobilization zone is capable of binding an interfering agent in the sample;

wherein said liquid sample flows from the sample receiving membrane and mixes with the mobile labeling reagent to move the mobile labeling reagent toward the control situs, and

observing a result of the assay.

56. The assay device of claim 55, wherein the flow is lateral flow.

57. The method of claim 55, wherein an accumulation of particles at the capture situs produces an indicative signal of the presence of the analyte in the sample.

58. The assay device of claim 55, wherein an accumulation of the interfering agent at the interfering agent immobilization zone does not produce a signal indicative of the presence of interfering agent in the sample.

59. A kit comprising:

an assay device comprising;

(a) a sample receiving membrane which conducts lateral flow of a liquid sample, in lateral flow contact with,

(b) an analyte detection membrane which conducts lateral flow of the sample comprising an interfering agent immobilization zone at a first situs, a conjugate forming membrane comprising a mobile labeling reagent at a labeling situs, and an immobile capture reagent at a capture situs, wherein the labeling reagent is capable of forming a complex with an analyte, the capture reagent is capable of binding an analyte-labeling reagent complex, and the interfering agent immobilization zone is capable of binding an interfering agent in the sample; and

instructions for use.