Procedure for quantitative and qualitative determination of chemical substances, based on molecular recognition and measurement of magnetic permeability

• US 6,110,660 A
• Filed: 05/01/1997
• Issued: 08/29/2000
• Est. Priority Date: 08/20/1995
• Status: Expired due to Term

• Current Assignee: LifeAssays AB
• Original Assignee: European Institute of Science AB
• Inventors: Berggren, Karin Marie Christine, Kriz, Dario
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US08/847,125
• Time in Patent Office: 1,216 Days
• Field of Search: 435/5, 435/7.1, 435/7.2, 435/4, 435/6, 422/50, 422/68.1, 422/69, 422/82.01, 436/501, 935/77, 935/78
• US Class Current: 435/4
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 2563/143 Magnetism, e.g. magnetic label
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence

Abstract

A system for very sensitive detection and/or quantification of an analyte is disclosed. The system is based on an interaction, such as specific binding or competitive displacement from a ligand, between an analyte and a ferromagnetic marker. The great difference in magnetic permeability between the ferromagnetic marker and the background allows detection of very small quantities of analyte, based on the marker'"'"'s induction of a changed magnetic permeability for the sample being measured.

Claims

1. A system for in vitro detection of an analyte, said system comprising a marker, a recognition element, and a transducer, and a vessel, said marker comprising a material having an externally, inductively detectable relative magnetic permeability constant of at least about 600, said recognition element being capable of binding to or competing for binding with said analyte in said vessel, and said transducer being adapted to be induced proportional to a magnetic permeability of a sample, wherein said transducer comprises a coil, and wherein said vessel containing said sample is introduced into said coil, wherein said marker and said recognition element act to induce in said transducer a first inductance value when said analyte is absent from said sample, and a second inductance value when said analyte is present in said sample.

2. The system of claim 1, wherein said marker specifically binds to said analyte.

3. The system of claim 1, wherein said marker competes with said analyte for binding to said recognition element.

4. The system of claim 1, wherein said recognition element is linked to said marker.

5. The system of claim 1, wherein said recognition element and said marker both bind to said analyte.

6. The system of claim 1, wherein said analyte comprises said marker.

7. The system of claim 1, wherein said analyte comprises a protein.

8. The system of claim 1, wherein said analyte comprises a nucleic acid.

9. The system of claim 1, wherein said analyte comprises a hormone.

10. The system of claim 1, wherein said analyte comprises an antibody.

11. The system of claim 1, wherein said analyte comprises a virus.

12. The system of claim 1, wherein said analyte comprises a cell.

13. The system of claim 1, wherein said second inductance value is quantitatively proportional to a concentration of said analyte in said sample.

14. The system of claim 1, wherein said sample comprises a soluble solution or a suspension.

15. The system of claim 14, wherein said sample comprises a centrifugation supernatant.

16. The system of claim 1, wherein said sample comprises a particulate fraction.

17. The system of claim 16, wherein said sample comprises a centrifugation pellet.

18. The system of claim 16, wherein said sample comprises cells.

19. The system of claim 16, wherein said sample comprises viruses.

20. The system of claim 16, wherein said sample comprises beads.

21. The system of claim 1, wherein said material comprises an element selected from the group consisting of iron, nickel, cobalt, gadolinium and manganese.

22. The system of claim 21, wherein said material is an alloy.

23. The system of claim 21, wherein said material is a semiconductor.

24. The system of claim 21, wherein said material is a chemical compound.

25. The system of claim 1, wherein said transducer comprises a coil adapted to accept inductance proportional to said magnetic permeability of said sample.

26. The system of claim 1, wherein said transducer comprises an electronic measuring bridge.

27. The system of claim 26, wherein said electronic measuring bridge comprises a Maxwell bridge.

28. The system of claim 1, wherein said transducer comprises an LC-circuit.

29. A method of detecting an analyte, comprising the steps of:

providing a sample, said sample comprising a marker and a recognition element, said marker comprising a material having an externally, inductively detectable relative magnetic permeability constant of at least about 600, said recognition element being capable of binding to or competing for binding with said analyte, said marker and said recognition element being adapted to cooperate to induce in a transducer comprising a coil a first inductance value when said analyte is absent from said sample, and a second inductance value when said analyte is present in said sample;

inducing an inductance value in said transducer by positioning said sample in said coil of said transducer in vitro; and

determining whether said analyte is absent or present in said sample, based on said inductance value induced in said inducing step.

30. The method of claim 29, wherein said marker specifically binds to said analyte.

31. The method of claim 29, wherein said marker competes with said analyte for binding to said recognition element.

32. The method of claim 29, wherein said recognition element is linked to said marker.

33. The method of claim 29, wherein said recognition element and said marker both bind to said analyte.

34. The method of claim 29, wherein said analyte comprises said marker.

35. The method of claim 29, wherein said analyte comprises a protein.

36. The method of claim 29, wherein said analyte comprises a nucleic acid.

37. The method of claim 29, wherein said analyte comprises a hormone.

38. The method of claim 29, wherein said analyte comprises an antibody.

39. The method of claim 29, wherein said analyte comprises a virus.

40. The method of claim 29, wherein said analyte comprises a cell.

41. The method of claim 29, wherein said second inductance value is quantitatively proportional to a concentration of said analyte in said sample.

42. The method of claim 29, wherein said sample comprises a soluble solution or a suspension.

43. The method of claim 42, wherein said sample comprises a centrifugation supernatant.

44. The method of claim 29, wherein said sample comprises a particulate fraction.

45. The method of claim 44, wherein said sample comprises a centrifugation pellet.

46. The method of claim 44, wherein said sample comprises cells.

47. The method of claim 44, wherein said sample comprises viruses.

48. The method of claim 44, wherein said sample comprises beads.

49. The method of claim 29, wherein said material comprises an element selected from the group consisting of iron, nickel, cobalt, gadolinium and manganese.

50. The method of claim 49, wherein said material is an alloy.

51. The method of claim 49, wherein said material is a semiconductor.

52. The method of claim 49, wherein said material is a chemical compound.

53. The method of claim 29, wherein said transducer comprises a coil adapted to accept inductance proportional to said magnetic permeability of said sample.

54. The method of claim 29, wherein said transducer comprises an electronic measuring bridge.

55. The method of claim 54, wherein said electronic measuring bridge comprises a Maxwell bridge.

56. The method of claim 29, wherein said transducer comprises an LC-circuit.

57. The method of claim 29, wherein said positioning comprises flowing said sample through said vicinity of said transducer.

58. A method for detecting the presence of an analyte, comprising the steps of:

contacting, in vitro, a sample suspected of containing said analyte with a reagent that binds to or competes for binding with or by said analyte, said reagent including a component having an externally, inductively detectable relative magnetic permeability constant of at least about 600;

separating unbound reagent from bound reagent; and

detecting or measuring the bound or unbound reagent as an indication of the presence, absence, or quantity of said analyte in said sample by placing said sample in a coil of a transducer adapted to be induced proportional to a magnetic permeability of said sample.