Method and apparatus for detecting biomolecular interactions

• US 20030032039A1
• Filed: 06/26/2002
• Published: 02/13/2003
• 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., DeFilippi, Frank
• Granted Patent: US 7,142,296 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• 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 2201/0635 Structured illumination, e.g. with grating
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides
• CPC Class Codes: G01N 2201/0833 Fibre array at detector, resolving
• CPC Class Codes: G01N 2201/0846 Fibre interface with sample, e.g. for spatial resolution
• CPC Class Codes: G01N 2201/1248 Validating from signal shape, slope, peak
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G02B 21/06 Means for illuminating specimens
• CPC Class Codes: G02B 5/1809 with pitch less than or comparable to the wavelength
• CPC Class Codes: G02B 5/1814 structurally combined with one or more further optical elements, e.g. lenses, mirrors, prisms or other diffraction gratings G02B5/189 takes precedence

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 apparatus for detecting biochemical interactions occurring on the surface of a biosensor includes a light source. A first optical fiber is coupled to the light source and illuminates the biosensor. A second optical fiber detects a wavelength reflected from the biosensor. A spectrometer determines spectra of a reflected signal from the biosensor.

Claims

1. An apparatus for detecting biochemical interactions occurring on a surface of a biosensor, said apparatus comprising:

a light source;

a first optical fiber coupled to said light source, said first optical fiber illuminating said biosensor,

a second optical fiber that detects a signal reflected from said surface of said biosensor; and

a spectrometer for determining spectra of said reflected signal from said biosensor.

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

3. The invention of claim 1 wherein said spectrometer is used to determine a peak wavelength value of said reflected signal.

4. The invention of claim 3 wherein said spectrometer is a single-point spectrometer.

5. The invention of claim 1 wherein said biosensor comprises a bottom portion of a fluid containing vessel.

6. The invention of claim 5 wherein said liquid containing vessel is selected from a group including a microtiter plate, a micro fluidic device, a microarray chip, a petri dish, a microscope slide, and a flask.

7. The invention of claim 1 wherein said reflected signal reflects from a surface of said biosensor.

8. The invention of claim 7 wherein said reflected signal reflects from a bottom surface of said biosensor.

9. The invention of claim 1 including a translation mechanism for moving said biosensor relative to said second optical fiber.

10. A biosensor imaging system comprising:

a light source generating white light;

a collimator for collimating said white light onto a surface of a biosensor;

an imaging spectrometer receiving reflected light from said biosensor, and software calculating a PWV of said reflected light.

11. The invention of claim 10 wherein said light source is a white light source.

12. The invention of claim 10 wherein said biosensor is arranged as an array of rows and columns of discrete detection areas.

13. The invention of claim 12 wherein said biosensor is coupled to a liquid containing vessel.

14. The invention of claim 10 wherein said illuminating optical fiber illuminates a bottom surface of said biosensor.

15. The invention of claim 10 wherein an optical fiber illuminates said biosensor.

16. The invention of claim 10 wherein said software enables a visual representation of said calculated PWV of said reflected light.

17. An instrument for detecting light reflected from a surface of a biosensor, said instrument comprising:

a light source;

an illuminating fiber optically coupled to said light source, said illuminating fiber illuminating an area of said surface of said biosensor,

a detecting fiber for detecting radiation reflected from said surface;

a spectrometer receiving said reflected radiation; and

software determining a peak wavelength value of said reflected wavelength.

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

a grating comprised of a material having a high refractive index; and

a substrate layer that supports said grating;

wherein, when said biosensor is illuminated a resonant grating effect is produced on said reflected radiation spectrum, and wherein said depth and period of said grating are less than said wavelength of the resonant grating effect.

19. The invention of claim 17, wherein a narrow band of optical wavelengths is reflected from said biosensor when the biosensor is illuminated with a broad band of optical wavelengths.

20. The invention of claim 17, wherein the optical device is a calorimetric resonant optical biosensor.

21. The invention of claim 20 wherein said colorimetric resonant optical biosensor is coupled to a liquid containing vessel.

22. The invention of claim 17 wherein the illuminating fiber and the detecting fiber are provided in a unitary optical fiber probe.

23. The invention of claim 22 wherein said optical fiber probe includes a collimating lens for collimating said quantity of white light.

24. The invention of claim 17 further comprising an incubator that incubates said biosensor at a predetermined temperature.

25. A method of measuring biochemical surface interactions of a biosensor, said method comprising the steps of:

incubating said biosensor at a predetermined temperature;

providing a dual fiber optic probe with at least one illuminating fiber that is optically coupled to a light source, said illuminating fiber directly illuminating light towards a reflective surface of said biosensor;

providing at least one detecting fiber, said at least one detecting fiber detecting light reflected from said reflective surface of the biosensor;

optically coupling said at least one detecting fiber to a spectrometer, and processing said reflected light from said reflective surface of said biosensor.

26. The invention of claim 25 further comprising a step of processing said reflected light from said reflective surface for determining a Peak Wavelength Value.

27. The invention of claim 25 including a step of generating a two-dimensional Peak Wavelength Value map of said sensor surface.

28. The invention of claim 25 further including a spectrometer that includes a one dimensional charge coupled device.

29. The invention of claim 25 further comprising a spectrometer for generating said two-dimensional Peak Wavelength Value map of said sensor surface.

30. The invention of claim 25 further including a step of providing a software interface that assists in controlling said spectrometer.

31. The invention of claim 30 wherein said software interface enables a visual representation of a Peak Wavelength Value.

32. An instrument for detecting a reflected wavelength, comprising:

a light source for generating a collimated quantity of white light;

an illuminating fiber optically coupled to said light source, said illuminating fiber lluminating an illumination area of a surface of an optical device;

a detecting fiber for detecting a reflected wavelength, said wavelength reflected from said surface of said optical device; and

a single-point spectrometer that processes said reflected wavelength and derives a peak wavelength value.

33. The invention of claim 32 further comprising a software interface that converts said detected reflected wavelength into a Peak Wavelength Value.