Method and instrument for detecting biomolecular interactions

• US 20030059855A1
• Filed: 06/26/2002
• Published: 03/27/2003
• Est. Priority Date: 10/30/2000
• Status: Active Grant

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Sru Biosystems Incorporated
• Inventors: Li, Peter Y., Cunningham, Brian T.
• Granted Patent: US 7,023,544 B2
• Time in Patent Office: Days
• US Class Current: 435/7.9
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: G01J 3/42 Absorption spectrometry; Double beam spectrometry; Flicker spectrometry; Reflection spectrometry beam switching arrangements G01J3/08
• CPC Class Codes: G01N 2021/7773 Reflection
• CPC Class Codes: G01N 2021/7776 Index
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/55 Specular reflectivity
• CPC Class Codes: G01N 21/75 Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73
• 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

Abstract

Method and apparatus for detecting biomolecular interactions. The use of labels is not required and the methods may be performed in a high-throughput manner. An instrument system for detecting a biochemical interaction on a biosensor. The system includes an array of detection locations comprises a light source for generating collimated white light. A beam splitter directs the collimated white light towards a surface of a sensor corresponding to the detector locations. A detection system includes an imaging spectrometer receiving the reflected light and generating an image of the reflected light.

Claims

1. An instrument system for detecting a biochemical interaction on a biosensor comprising an array of detection locations, said system comprising:

a light source for generating collimated white light;

a beam splitter directing said collimated white light towards a surface of a sensor corresponding to said detector locations; and

a detection system including an imaging spectrometer receiving said reflected light and generating an image of said reflected light.

2. The invention of claim 1 wherein said biosensor is a microarray chip.

3. The invention of claim 2 wherein said microarray chip is a conventional microarray chip.

4. The invention of claim 1 wherein said biosensor is transported along a scan direction.

5. The invention of claim 1 wherein said imaging spectrometer generates a Peak Wavelength Value image.

6. The invention of claim 1 wherein said directed collimated white light is directed to a plurality of locations on said surface of said sensor.

7. The invention of claim 1 wherein said directed collimated white light is simultaneously directed to a plurality of locations on said surface of said sensor.

8. The invention of claim 1 wherein said directed collimated white light is directed to an imaging area on said surface of said sensor.

9. The invention of claim 2 wherein said directed collimated white light illuminates a plurality of wells of said microarray chip.

10. The invention of claim 1 wherein said imaging spectrometer includes a two-dimensional Charge Coupled Device camera.

11. The invention of claim 1 wherein said imaging spectrometer includes a diffraction grating.

12. The invention of claim 1 including a software interface, said software interface controlling said imaging spectrometer.

13. The invention of claim 12 wherein said software interface coordinates Peak Wavelength Value determination with an x-y motion stage.

14. The invention of claim 12 wherein said software interface converts measured data into a Peak Wavelength Value.

15. The invention of claim 1, wherein said light source illuminates said biosensor from a sensor top surface

16. The invention of claim 1 wherein said light source illuminates said biosensor from a sensor bottom surface.

17. An instrument for calculating a peak wavelength, said instrument comprising:

an incubator assembly for incubating a biosensor;

an optical assembly, said optical assembly illuminating said biosensor with light and collecting reflected radiation from said biosensor;

a spectrometer receiving said reflected radiation; and

software deriving a peak wavelength from said reflected and detected wavelength.

18. The invention of claim 17 wherein said biosensor is embedded within a bottom portion of a microtiter plate.

19. The invention of claim 17 wherein said collimator assembly comprises a plurality of fiber optic probes.

20. The invention of claim 18 wherein said plurality of fiber optic probes comprise an illuminating fiber optic probe for illuminating said biosensor and a detecting fiber optic probe for detecting said reflected wavelength.

21. The invention of claim 18 wherein said collimator assembly comprises a beam splitter, said beam splitter enables said illuminated light and said reflected light to share a common optical path.

22. The invention of claim 17 wherein said collimator assembly includes a collimating lens, said collimating lens focuses said white light on said biosensor surface.

23. The invention of claim 17 wherein said biosensor comprises:

a first two-dimensional grating comprising a first refractive index material and having a top surface and a bottom surface;

a substrate layer comprising a top surface and a bottom surface, wherein said top surface of said substrate supports said bottom surface of said first two-dimensional grating; and

a second two-dimensional grating comprising a second refractive index material and having a top surface and a bottom surface, wherein said bottom surface of said second two-dimensional grating is attached to said bottom surface of said substrate;

wherein, when said biosensor is illuminated two resonant grating effects are produced in said reflected radiation spectrum, and wherein said depth and period of both of said two-dimensional gratings are less than said wavelength of said resonant grating effects.