Optical assay technique

• US 4,931,384 A
• Filed: 10/17/1984
• Issued: 06/05/1990
• Est. Priority Date: 12/21/1982
• Status: Expired due to Term

• Current Assignee: Applied Research Systems ARS Holding NV (Merck & Co., Inc.)
• Original Assignee: Ares-Serono NV
• Inventors: Smith, Alan M., Fisher, John H., Pettigrew, Robert M., Petty-Saphon, Satham, Layton, Derek G.
• Primary Examiner(s): Kepplinger, Esther M.
• Application Number:
  US06/643,141
• Time in Patent Office: 2,057 Days
• Field of Search: 436/518, 436/524, 436/527, 436/528, 436/536, 436/537, 436/163, 436/805, 436/810, 436/73, 436/74, 436/164, 436/171, 436/525, 436/531, 436/548, 356/317, 356/318, 356/417, 356/461.1, 356/461.2, 356/305, 435/7, 435/805, 435/808, 427/2
• US Class Current: 435/7.31
• CPC Class Codes: G01N 21/554 detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

An assay technique for qualitative and quantitative detection of a chemcial, biochemical or biological detection of a chemical, biochemical or biological species in sample. The technique comprises (a) coating at least a predetermined part of a pre-formed surface on a substrate with a thin film of a material capable of binding the species to be assayed, the pre-formed surface being optically active with respect to radiation at least over a predetermined band of wavelengths; (b) contacting the coated surface with sample; and (c) observing the optical properties of said pre-formed surface in order to determine a qualitative and quantitative change in optical properties as a result of the binding of the species onto said thin film of material. The optical properties of the pre-formed surface may be observed before and after step (b) in order to determine any change in optical properties, or they may be monitored during step (b). The pre-formed surface is preferably a grating. An article for use in the above technique is also disclosed, and comprises a substrate carrying said pre-formed surface which in turn is coated with the respective material for the species to be assayed.

Claims

1. An assay technique for qualitative and quantitative detection of a chemical, biochemical or biological species in a sample, which comprises:

(a) coating at least a predetermined part of a surface having a pre-formed regular periodic surface structure provided on a substrate with a thin film of a material capable of binding the species to be assayed, said surface producing a reflective dip with respect to a parameter of incident polarized light;

(b) contacting the coated surface with the sample;

(c) directing polarized light at said coated surface; and

(d) measuring the change in the reflective dip as a result of the binding of the species onto said thin film of material, whereby a quantitative measure of the species being assayed is provided.

2. A method according to claim 1, wherein the reflective dip is measured before and after step (b) in order to determine the said change.

3. A method according to claim 1, wherein the reflective dip is monitored with respect to changes in the angle of incidence or wavelength of the incident polarized light.

4. A method according to claim 1, wherein said pre-formed regular periodic surface structure is a diffraction grating.

5. A method according to claim 4, wherein the grating is of square-wave profile.

6. A method according to claim 4, wherein the grating is of sinusoidal profile.

7. A method according to claim 4, wherein the grating is of saw-tooth profile.

8. A method according to claim 4, wherein the grating has a depth (peak-to-trough) in the range 10 to 50 nanometers.

9. A method according to claim 8, wherein the pitch (period) of the grating is greater than its depth.

10. A method according to claim 4, wherein the grating has a depth (peak-to-trough) in the range 50 to 200 nanometers.

11. A method according to claim 10, wherein the pitch (period) of the grating is of the same order as its depth.

12. A method according to claim 4, wherein the grating has a depth (peak-to-trough) in the range 200 to 2000 nanometers.

13. A method according to claim 1, wherein said pre-formed regular periodic surface structure comprises two or more diffraction gratings disposed mutually at an angle.

14. A method according to claim 1, wherein said surface is structured so that it is reflective with respect to radiation of wavelengths from 700 to 1500 nanometers.

15. A method according to claim 1, wherein said surface is structured so that it is reflective with respect to radiation of wavelengths from 350 to 700 nanometers.

16. A method according to claim 1, wherein at least the active surface of the substrate is comprised of a metal or a metal layer.

17. A method according to claim 16, wherein said metal is gold, silver, copper or aluminum.

18. A method according to claim 1, wherein the active surface of the substrate is comprised of an inorganic oxide or a layer thereof.

19. A method according to claim 18, wherein said inorganic oxide is an oxide of silver, copper or aluminum.

20. A method according to claim 1, wherein the substrate is in strip-form.

21. A method according to claim 1, wherein one zone of said surface distinct from said predetermined part of the surface on the substrate is left free of the coating material and is not contacted, in step (b), by the sample.

22. A method according to claim 21, wherein a two-beam illuminating system is employed in step (c), one of said beams being directed at said one zone of said surface, and the other of the two beams being directed at said predetermined surface part.

23. A method according to claim 1, wherein one zone of said surface distinct from said predetermined part of the surface is left free of the coating material and the whole of said surface, including said one zone, is contacted, in step (b), by the sample.

24. A method according to claim 3 wherein the polarized light is monochromatic and the parameter of the light monitored is its angle of incidence.

25. A method according to claim 1, wherein the species which is to be detected is an antigen.

26. A method according to claim 25, wherein the material capable of binding said species comprises antibodies for the antigen which is to be assayed.

27. A method according to claim 26, wherein said antibodies are monoclonal antibodies.

28. A method according to claim 11, wherein the species which is to be assayed is an ionic species.

29. A method according to claim 28, wherein said ionic species is a metal ion.

30. A method according to claim 28, wherein the material capable of binding the species to be assayed is a chemical, enzyme or a organism.

31. A method according to claim 30, wherein said chemical, enzyme or organism is one or more of:

a polypeptide, a steroid, a saccharide or polysaccharide, a proteoglycan, a nucleotide, a nucleic acid, a protonucleic acid, a microbial cell or a yeast.

32. A method according to claim 1, wherein said thin film of material is firmly bonded to said surface.

33. A method according to claim 1, wherein said preformed regular periodic surface structure comprises a regular periodic array of protuberances.

34. A method according to claim 33, in which said surface is washed immediately after being contacted with the sample and before the observations in step (c).

35. A method according to claim 34, in which said surface is covered with a layer of a liquid of high refractive index between steps (b) and (c).

36. A method according to claim 1, in which said surface is washed immediately after being contacted with the sample and before the observations in step (d).

37. A method according to claim 36, in which said surface is covered with a layer of a liquid of high refractive index between steps (b) and (c).

72. An article as claimed in claim 24, wherein the surface is in strip-form.

38. An assay technique for qualitative and quantitative detection of a chemical, biochemical or biological species in a sample, which comprises:

(a) coating at least a predetermined part of a surface having a pre-formed single diffraction grating or two or more gratings disposed mutually at an angle provided on a substrate with a thin film of a material capable of binding the species to be assayed, said surface suppressing the transmission of zero-order diffracted light at least over a predetermined band of wavelengths;

(b) contacting the coated surface with the sample; and

(c) measuring the change in transmission of zero-order diffracted light as a result of the binding of the species onto said thin film of material, whereby a quantitative measure of the species being assayed is provided.

39. A method according to claim 38, wherein the transmission of said surface is measured before and after step (b) in order to determine the said change in transmission.

40. A method according to claim 38, wherein the transmission of said surface is monitored during step (b) in order to determine the said change in transmission.

41. A method according to claim 38, wherein the grating is of square-wave profile.

42. A method according to claim 38, wherein the grating is of sinusoidal profile.

43. A method according to claim 38, wherein the grating is of saw-tooth profile.

44. A method according to claim 38, wherein the grating has a depth (peak-to-trough) in the range 10 to 50 nanometers.

45. A method according to claim 44, wherein the pitch (period) of each grating is greater than their depth.

46. A method according to claim 38, wherein the grating has a depth (peak-to-trough) in the range 50 to 200 nanometers.

47. A method according to claim 46, wherein the pitch (period) of each grating is of the same order as their depth.

48. A method according to claim 38, wherein the grating has a depth (peak-to-trough) in the range 200 to 2000 nanometers.

49. A method according to claim 38, wherein the substrate is formed of a plastic material.

50. A method according to claim 49, wherein said plastic material is a material which is curable by ultra-violet light.

51. A method according to claim 49, wherein said plastic material is an acrylic or a polyester material.

52. A method according to claim 51, wherein said plastic material is polymethylmethacrylate.

53. A method according to claim 49, wherein the plastic material has a refractive index in the range 1.25 to 1.6.

54. A method according to claim 53 wherein the refractive index of said plastic material is about 1.4.

55. A method according to claim 38, wherein the substrate is a glass coated with a synthetic polymeric material.

56. A method according to claim 38, wherein the active surface of the substrate is constituted by an inorganic oxide or a layer thereof.

57. A method according to claim 38, wherein the substrate is in strip-form.

58. A method according to claim 38 wherein one zone of said surface distinct from said predetermined part of the surface on the substrate is left free of the coating material and is not contacted, in step (b), by the sample.

59. A method according to claim 58, wherein a two-beam illuminating system is employed in step (c), one of said beams being directed at said one zone of said surface, and the other of the two beams being directed at said predetermined surface part.

60. A method according to claim 38, wherein one zone of said surface distinct from said predetermined part of the surface is left free of the coating material and the whole of said surface, including said one zone, is contacted, in step (b), by the sample.

61. A method according to claim 38, wherein in step (c) monochromatic radiation is used.

62. A method according to claim 38, wherein the species which is to be detected is an antigen.

63. A method according to claim 62, wherein the material capable of binding said species comprises antibodies for the antigen which is to be assayed.

64. A method according to claim 63, wherein said antibodies are monoclonal antibodies.

65. A method according to claim 38, wherein the species which is to be assayed is an ionic species.

66. A method according to claim 65, wherein said ionic species is a metal ion.

67. A method according to claim 65, wherein the material capable of binding the species to be assayed is a chemical, enzyme or a organism.

68. A method according to claim 67, wherein said chemical, enzyme or organism is one or more of:

a polypeptide, a steroid, a saccharide or polysaccharide, a proteoglycan, a nucleotide, a nucleic acid, a protonucleic acid, a microbial cell or a yeast.

69. A method according to claim 38, wherein said thin film of material is firmly bonded to said surface.

70. An article for use in an assay technique for qualitative and quantitative detection of a chemical, biochemical or biological species in a sample, which comprises a surface with a regular periodic pre-formed surface structure reflective of polarized light at least over a pre-determined band of wavelengths, and said surface including a metal layer capable of supporting surface plasmon resonance, at least a pre-determined part of said surface including the metal layer being coated with a thin film of a material capable of binding the species to be assayed.

71. An article as claimed in claim 70, wherein the surface is lamellar.

73. An article as claimed in claim 70, wherein the preformed surface structure is a diffraction grating of square-wave, sinusoidal or saw-tooth profile.

74. An article as claimed in claim 70, wherein the preformed surface structure comprises a regular periodic array of protuberances.

75. An article as claimed in claim 70, wherein said metal is gold, silver, copper or aluminum.

76. An article as claimed in claim 70, wherein said surface is constituted by an inorganic oxide.

77. An article as claimed in claim 76, wherein said oxide is an oxide of silver, copper or aluminum.

78. An article as claimed in claim 70, wherein said thin film of material comprises antibodies.

79. An article as claimed in claim 70, wherein said thin film of material comprises a chemical enzyme or an organism.

80. An article as claimed in claim 70, wherein said surface is constituted by a layer at least 5 nanometers in thickness.

81. An article as claimed in claim 70, wherein the article includes a plurality of zones each of which is coated with a different receptive material so that the article is capable of binding a plurality of different species.

82. An assay technique for qualitative and quantitative detection of a chemical, biochemical or biological species in a sample, which comprises:

(i) contacting the surface of an article as claimed in claim 70 with the sample; and

(ii) measuring the change in surface plasmon resonance of the surface of said article as a result of the binding of the chemical, biochemical or biological species onto said surface whereby a quantitative measure of the species being assayed is provided.