Label-Free High-Throughput Optical Technique for Detecting Biomolecular Interactions

• US 20090148955A1
• Filed: 12/02/2008
• Published: 06/11/2009
• Est. Priority Date: 10/30/2000
• Status: Abandoned Application

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Cunningham, Brian, Lin, Bo, Li, Peter, Pien, Homer, Pepper, Jane
• Application Number:
  US12/326,237
• Publication Number:
  US 20090148955A1
• Time in Patent Office: Days
• US Class Current: 436/164
• 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: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

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 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 a biosensor comprising;

(i) a linear grating layer having a depth and a period comprised of a material having a high refractive index;

(ii) a low refractive index material layer that supports the linear grating layer; and

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

wherein, when the biosensor is illuminated a resonant grating effect is produced on a transmitted radiation spectrum, and wherein the depth and the period of the linear grating layer are less than the wavelength of the resonant grating effect;

(b) illuminating the biosensor with light; and

(c) detecting a minimum in the spectrum of transmitted wavelength of light from the biosensor;

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

2. The method of claim 1, wherein the one or more specific binding substances and their binding partners are detection label-free.

3. The method of claim 1, wherein the one or more binding partners comprise one or more tags comprising biotin, succinimidyl-6-[a-methyl-a-(2-pyridyl-dithio) toluamido] hexanoate (SMPT), dimethylpimelimidate (DMP), or histidine.

4. The method of claim 3, wherein the one or more tags are reacted with streptavidin, horseradish peroxidase, or streptavidin coated nanoparticles, before the step of illuminating the biosensor with light.

5. The method of claim 1, wherein the low refractive index material layer comprises glass, plastic, or epoxy.

6. The method of claim 1, wherein the linear grating layer is comprised of zinc sulfide, titanium dioxide, indium tin oxide, tantalum oxide, or silicon nitride.

7. The method of claim 1, wherein the one or more specific binding substances are arranged in an array of distinct locations on the linear grating layer.

8. The method of claim 1, wherein the amount of the one or more binding partners is determined.

9. The method of claim 1, wherein the biosensor is illuminated from its top surface or from its bottom surface.

10. A detection system comprising:

(a) a biosensor comprising (i) a linear grating layer having a depth and a period comprised of a material having a high refractive index;

(ii) a low refractive index material layer that supports the linear grating layer; and

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

wherein, when the biosensor is illuminated a resonant grating effect is produced on a transmitted radiation spectrum, and wherein the depth and the period of the linear grating layer is less than the wavelength of the resonant grating effect;

(b) a light source that directs light to the biosensor; and

(c) a detector that detects light transmitted through the biosensor.

11. The detection system of claim 10, wherein the low refractive index material layer comprises glass, plastic, or epoxy.

12. The detection system of claim 10, wherein the linear grating layer is comprised of zinc sulfide, titanium dioxide, indium tin oxide, tantalum oxide, or silicon nitride.

13. The detection system of claim 10, wherein the one or more specific binding substances are arranged in an array of distinct locations on the linear grating layer.

14. The detection system of claim 10, wherein the amount of the one or more binding partners is determined.

15. The detection of claim 10, wherein the light source illuminates the biosensor from its top surface or from its bottom surface.