Guided mode resonant filter biosensor using a linear grating surface structure

• US 20030027328A1
• Filed: 01/28/2002
• Published: 02/06/2003
• Est. Priority Date: 10/30/2000
• Status: Active Grant

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Lin, Bo, Li, Peter, Cunningham, Brian T., Pien, Homer, Pepper, Jane, Qiu, Jean
• Granted Patent: US 7,070,987 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• 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: G02B 5/1809 with pitch less than or comparable to the wavelength
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

Methods and compositions are provided for detecting biomolecular interactions. The use of labels is not required and the methods can be performed in a high-throughput manner. The invention also provides optical devices useful as narrow band filters.

Claims

1. A biosensor comprising:

(a) a one-dimensional grating layer comprised of a material having a high refractive index;

(b) a low refractive index material layer that supports the one-dimensional grating layer; and

(c) one or more specific binding substances immobilized on the surface of the one-dimensional grating layer opposite of the low refractive index material layer;

wherein, when the biosensor is illuminated a resonant grating effect is produced on a reflected radiation spectrum, and wherein cross-section of the one-dimensional grating is less than the wavelength of the resonant grating effect.

2. The biosensor of claim 1, wherein the cross-sectional profile of the one-dimensional grating is triangular, sinusoidal, trapezoidal, rectangular, v-shaped, u-shaped, upside-down u-shaped, upside-down v-shaped, stepped or square.

3. The biosensor of claim 1, wherein a narrow band of optical wavelengths is reflected from the biosensor when the biosensor is illuminated with a broad band of optical wavelengths.

4. The biosensor of claim 1, wherein the low refractive index material comprises glass, plastic, polymer, or epoxy.

5. The biosensor of claim 1, wherein the one-dimensional grating is comprised of a material selected from the group consisting of zinc sulfide, titanium dioxide, indium tin oxide, tantalum oxide, and silicon nitride.

6. The biosensor of claim 1, wherein the one-dimensional grating has a period of about 0.01 microns to about 1 micron and a depth of about 0.01 microns to about 1 micron.

7. The biosensor of claim 1, wherein the one or more specific binding substances are arranged in an array of distinct locations.

8. The biosensor of claim 1, wherein the one or more specific binding substances are immobilized on the one-dimensional grating by physical adsorption or by chemical binding.

9. The biosensor of claim 7, wherein the distinct locations define a microarray spot of about 10-500 microns in diameter.

10. The biosensor of claim 1, wherein the one or more specific binding substances are bound to their binding partners.

11. The biosensor of claim 1, wherein the one or more specific binding substances are selected from the group consisting of nucleic acids, polypeptides, antigens, polyclonal antibodies, monoclonal antibodies, single chain antibodies (scFv), F(ab) fragments, F(ab′

)₂ fragments, Fv fragments, small organic molecules, cells, viruses, bacteria, polymers, peptide solutions, protein solutions, chemical compound library solutions, single-stranded DNA solutions, double-stranded DNA solutions, RNA solutions, and biological samples.

12. The biosensor of claim 11, wherein the biological sample is selected from the group consisting of blood, plasma, serum, gastrointestinal secretions, homogenates of tissues or tumors, synovial fluid, feces, saliva, sputum, cyst fluid, amniotic fluid, cerebrospinal fluid, peritoneal fluid, lung lavage fluid, semen, lymphatic fluid, tears, and prostatitc fluid.

13. The biosensor of claim 10, wherein the binding partners are selected from the group consisting of nucleic acids, polypeptides, antigens, polyclonal antibodies, monoclonal antibodies, single chain antibodies (scFv), F(ab) fragments, F(ab′

)₂ fragments, Fv fragments, small organic molecules, cells, viruses, bacteria, polymers, peptide solutions, protein solutions, chemical compound library solutions, single-stranded DNA solutions, double-stranded DNA solutions, RNA solutions and biological samples.

14. The biosensor of claim 13, wherein the biological sample is selected from the group consisting of blood, plasma, serum, gastrointestinal secretions, homogenates of tissues or tumors, synovial fluid, feces, saliva, sputum, cyst fluid, amniotic fluid, cerebrospinal fluid, peritoneal fluid, lung lavage fluid, semen, lymphatic fluid, tears, and prostatitc fluid.

15. A liquid-containing vessel comprising the biosensor of claim 1 as an internal surface.

16. The liquid-containing vessel of claim 15, wherein the vessel is selected from the group consisting of a microtiter plate, a test tube, a petri dish and a microfluidic channel.

17. A detection system comprising the biosensor of claim 1, a light source that directs light to the biosensor, and a detector that detects light reflected or transmitted from the biosensor, wherein a polarizing filter occurs between the light source and the biosensor.

18. A method of detecting the binding of one or more specific binding substances to their respective binding partners comprising:

(a) applying one or more binding partners to the biosensor of claim 1;

(b) illuminating the biosensor with light; and

(c) detecting a peak wavelength value (PWV);

wherein, if the one or more specific binding substances have bound to their respective binding partners, then the PWV is shifted.

19. A method of detecting the binding of one or more specific binding substances to their respective binding partners comprising:

(a) applying one or more binding partners to the biosensor of claim 1, wherein the one-dimensional grating is coated with an array of distinct locations containing the one or more specific binding substances;

(b) illuminating each distinct location of the biosensor with light; and

(c) detecting peak wavelength value (PWV) for each distinct location of the biosensor;

wherein, if the one or more specific binding substances have bound to their respective binding partners at a distinct location, then the PWV is shifted.

20. A method of detecting activity of an enzyme comprising:

(a) applying one or more enzymes to the biosensor of claim 1;

(b) washing the biosensor;

(c) illuminating the biosensor with light; and

(d) detecting a PWV;

wherein, if the one or more enzymes have altered the one or more specific binding substances of the biosensor by enzymatic activity, then the PWV is shifted.

21. A method of measuring the amount of one or more binding partners in a test sample comprising:

(a) illuminating the biosensor of claim 1 with light;

(b) detecting a PWV from the biosensor;

(c) applying a test sample comprising one or more binding partners to the biosensor;

(d) illuminating the biosensor with light; and

(e) detecting a PWV from the biosensor;

wherein, the difference in PWV in step (b) and step (e) is a measurement of the amount of one or more binding partners in the test sample.

22. A method of detecting the binding of one or more specific binding substances to their respective binding partners comprising:

(a) applying one or more binding partners comprising one or more tags to the biosensor of claim 1;

(b) illuminating the biosensor with light; and

(c) detecting a PWV from the biosensor;

wherein, if the one or more specific binding substances have bound to their respective binding partners, then the reflected wavelength of light is shifted.

23. The method of claim 22, wherein the one or more tags are selected from the group consisting of biotin, succinimidyl-6-[a-methyl-a-(2-pyridyl-dithio) toluamido] hexanoate (SMPT), dimethylpimelimidate (DMP), and histidine.

24. The method of claim 22, wherein the one or more tags are reacted with a composition selected from the group consisting of streptavidin, horseradish peroxidase, and streptavidin coated nanoparticles, before the step of illuminating the biosensor with light.

33. The biosensor of claim 31, wherein the distinct locations define a microarray spot of about 10-500 microns in diameter.

25. A biosensor comprising:

(a) a one-dimensional grating surface structure comprised of a material having a low refractive index;

(b) a high refractive index material layer that is applied on top of the low refractive index one-dimensional grating layer; and

(c) one or more specific binding substances immobilized on a surface of the high refractive index layer opposite of the one-dimensional grating surface structure comprised of a material having a low refractive index;

wherein, when the biosensor is illuminated a resonant grating effect is produced on a reflected radiation spectrum, and wherein cross-section of the one-dimensional grating is less than the wavelength of the resonant grating effect.

26. The biosensor of claim 25, wherein the cross-sectional profile of the one-dimensional grating is triangular, sinusoidal, trapezoidal, rectangular, v-shaped, u-shaped, upside-down u-shaped, upside-down v-shaped, stepped or square.

27. The biosensor of claim 25, wherein a narrow band of optical wavelengths is reflected from the biosensor when the biosensor is illuminated with a broad band of optical wavelengths.

28. The biosensor of claim 25, wherein the low refractive index material comprises glass, plastic, polymer, or epoxy.

29. The biosensor of claim 25, wherein the high refractive index material is selected from the group consisting of zinc sulfide, titanium dioxide, indium tin oxide, tantalum oxide, and silicon nitride.

30. The biosensor of claim 25, wherein the one-dimensional grating has a period of about 0.01 microns to about 1 micron and a depth of about 0.01 microns to about 1 micron.

31. The biosensor of claim 25, wherein the one or more specific binding substances are arranged in an array of distinct locations.

32. The biosensor of claim 25, wherein the one or more specific binding substances are immobilized on the high refractive index material by physical adsorption or by chemical binding.

34. The biosensor of claim 25, wherein the one or more specific binding substances are bound to their binding partners.

35. The biosensor of claim 25, wherein the one or more specific binding substances are selected from the group consisting of nucleic acids, polypeptides, antigens, polyclonal antibodies, monoclonal antibodies, single chain antibodies (scFv), F(ab) fragments, F(ab′

)₂ fragments, Fv fragments, small organic molecules, cells, viruses, bacteria, polymers, peptide solutions, protein solutions, chemical compound library solutions, single-stranded DNA solutions, double-stranded DNA solutions, RNA solutions, and biological samples.

36. The biosensor of claim 35, wherein the biological sample is selected from the group consisting of blood, plasma, serum, gastrointestinal secretions, homogenates of tissues or tumors, synovial fluid, feces, saliva, sputum, cyst fluid, amniotic fluid, cerebrospinal fluid, peritoneal fluid, lung lavage fluid, semen, lymphatic fluid, tears, and prostatitc fluid.

37. The biosensor of claim 34, wherein the binding partners are selected from the group consisting of nucleic acids, polypeptides, antigens, polyclonal antibodies, monoclonal antibodies, single chain antibodies (scFv), F(ab) fragments, F(ab′

)₂ fragments, Fv fragments, small organic molecules, cells, viruses, bacteria, polymers, peptide solutions, protein solutions, chemical compound library solutions, single-stranded DNA solutions, double-stranded DNA solutions, RNA solutions and biological samples.

38. The biosensor of claim 37, wherein the biological sample is selected from the group consisting of blood, plasma, serum, gastrointestinal secretions, homogenates of tissues or tumors, synovial fluid, feces, saliva, sputum, cyst fluid, amniotic fluid, cerebrospinal fluid, peritoneal fluid, lung lavage fluid, semen, lymphatic fluid, tears, and prostatitc fluid.

39. A liquid-containing vessel comprising the biosensor of claim 25 as an internal surface.

40. The liquid-containing vessel of claim 39, wherein the vessel is selected from the group consisting of a microtiter plate, a test tube, a petri dish and a microfluidic channel.

41. A detection system comprising the biosensor of claim 25, a light source that directs light to the biosensor, and a detector that detects light reflected or transmitted from the biosensor, wherein a polarizing filter occurs between the light source and the biosensor.

42. A method of detecting the binding of one or more specific binding substances to their respective binding partners comprising:

(a) applying one or more binding partners to the biosensor of claim 25;

(b) illuminating the biosensor with light; and

(c) detecting a peak wavelength value (PWV);

wherein, if the one or more specific binding substances have bound to their respective binding partners, then the PWV is shifted.

43. A method of detecting the binding of one or more specific binding substances to their respective binding partners comprising:

(a) applying one or more binding partners to the biosensor of claim 25, wherein the high refractive index material is coated with an array of distinct locations containing the one or more specific binding substances;

(b) illuminating each distinct location of the biosensor with light; and

(c) detecting peak wavelength value (PWV) for each distinct location of the biosensor;

wherein, if the one or more specific binding substances have bound to their respective binding partners at a distinct location, then the PWV is shifted.

44. A method of detecting activity of an enzyme comprising:

(a) applying one or more enzymes to the biosensor of claim 25;

(b) washing the biosensor;

(c) illuminating the biosensor with light; and

(d) detecting a PWV;

wherein, if the one or more enzymes have altered the one or more specific binding substances of the biosensor by enzymatic activity, then the PWV is shifted.

45. A method of measuring the amount of one or more binding partners in a test sample comprising:

(a) illuminating the biosensor of claim 25 with light;

(b) detecting a PWV from the biosensor;

(c) applying a test sample comprising one or more binding partners to the biosensor;

(d) illuminating the biosensor with light; and

(e) detecting a PWV from the biosensor;

wherein, the difference in PWV in step (b) and step (e) is a measurement of the amount of one or more binding partners in the test sample.

46. A method of detecting the binding of one or more specific binding substances to their respective binding partners comprising:

(a) applying one or more binding partners comprising one or more tags to the biosensor of claim 25;

(d) illuminating the biosensor with light; and

(e) detecting a PWV from the biosensor;

wherein, if the one or more specific binding substances have bound to their respective binding partners, then the reflected wavelength of light is shifted.

47. The method of claim 46, wherein the one or more tags are selected from the group consisting of biotin, succinimidyl-6-[a-methyl-a-(2-pyridyl-dithio) toluamido] hexanoate (SMPT), dimethylpimelimidate (DMP), and histidine.

48. The method of claim 46, wherein the one or more tags are reacted with a composition selected from the group consisting of streptavidin, horseradish peroxidase, and streptavidin coated nanoparticles, before the step of illuminating the biosensor with light.

49. A biosensor comprising:

(a) a one-dimensional or two-dimensional grating layer comprised of a material having a high refractive index;

(b) a low refractive index material layer that supports the one-dimensional or two-dimensional grating layer;

(c) a surface modification layer on a surface of the one-dimensional or two-dimensional grating layer opposite of the low refractive index material layer; and

(d) one or more specific binding substances immobilized on a surface of the surface modification layer opposite of the one-dimensional or two-dimensional grating layer;

wherein, when the biosensor is illuminated a resonant grating effect is produced on a reflected radiation spectrum.

50. The biosensor of claim 49, wherein the surface modification layer is comprised of silicon oxide.

51. The biosensor of claim 49, wherein the thickness of the surface modification layer is about 5 nm to about 15 nm.

53. The biosensor of claim 51, wherein the interfacial layer is comprised of a material selected from the group consisting of silicon oxide, silicon oxynitride, borosilicate glass, phosophosilicate glass, pyrex, glass, and a metal oxide.

54. The biosensor of claim 51, wherein the interfacial layer is about 1 mn to about 200 nm thick.

52. A biosensor comprising:

(a) a grating layer comprising a one-dimensional or two-dimensional grating on a first surface;

(b) a interfacial layer on the first surface of the grating layer;

(c) a high refractive index material layer on the surface of the interfacial layer opposite of the grating layer; and

(d) one or more specific binding substances immobilized on a surface of the high refractive index material layer opposite of the interfacial layer;

wherein, when the biosensor is illuminated a resonant grating effect is produced on a reflected radiation spectrum.