Resonant optical cavities for high-sensitivity high-throughput biological sensors and methods

• US 7,384,797 B1
• Filed: 10/12/2000
• Issued: 06/10/2008
• Est. Priority Date: 10/12/2000
• Status: Expired due to Fees

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Blair, Steven M.
• Primary Examiner(s): Chin; Christopher L
• Application Number:
  US10/089,497
• Time in Patent Office: 2,798 Days
• Field of Search: None
• US Class Current: 436/524
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7746 the waveguide coupled to a cavity resonator
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

Biosensors including resonant optical cavities. The resonant optical cavities are shaped so as to generate whispering gallery modes, which increase the quality factors of the cavities and facilitate the detection of analytes in a sample with enhanced sensitivity. The sizes of the resonant optical cavities facilitate their use in biosensors that include arrays of sensing zones. Accordingly, the resonant optical cavities may be used in high-density sensing arrays that can be read in real-time and in parallel. Thus, the resonant optical cavities are useful for detecting small concentrations of samples in real-time and with high throughput. Different embodiments of the biosensors are also disclosed, as are methods for using the biosensors.

Claims

1. A biosensor, comprising a resonant optical cavity with a circular cross section and a substantially planar, circular end surface, the resonant optical cavity also having a quality factor of at least about 10⁴.

2. The biosensor of claim 1, wherein the resonant optical cavity is part of an array of resonant optical cavities.

3. The biosensor of claim 1, further comprising a transmission port adjacent a surface of said of least one resonant optical cavity and configured to transmit electromagnetic radiation into said at least one resonant optical cavity.

4. The biosensor of claim 1, further comprising at least one capture substrate immobilized on or adjacent to a surface of said resonant optical cavity.

5. The biosensor of claim 4, comprising a plurality of types of capture substrates immobilized on or adjacent to said surface.

6. The biosensor of claim 5, wherein said plurality of types of capture substrates are immobilized on or adjacent to different regions of said surface.

7. The biosensor of claim 4, further comprising a sensor configured to detect binding of said at least one capture substrate with analyte or a molecule that competes with said analyte.

8. The biosensor of claim 4, further comprising a sensor for detecting at least one mass and fluorescence.

9. A biosensor, comprising a resonant optical cavity having a quality factor of at least about 10⁷.

10. A biosensor comprising a resonant cavity having a transmission port adjacent a surface of said resonant optical cavity and configured to transmit electromagnetic radiation into said resonant optical cavity wherein said transmission port comprises a waveguide distribution network configured to transmit electromagnetic radiation into a plurality of resonant optical cavities, said waveguide distribution network including at least one of a bus network and a combination tree-buss network.

11. A biosensor, comprising a resonant optical cavity, said resonant optical cavity being a doubly resonant.

12. A biosensor, comprising a resonant optical cavity, said resonant optical cavity being capable of generating whispering gallery modes and comprising at lease one of a microfabricated resonant optical cavity and a bulk resonant optical cavity, and further comprising:

a source of electromagnetic radiation;

a transmission port in communication with said source and disposed adjacent a surface of said resonant optical cavity so as to transmit electromagnetic radiation into said resonant optical cavity;

at least one capture substrate immobilized on or adjacent to a substantially defect free surface of said resonant optical cavity; and

a sensor configured to detect at least one of a mass of molecules immobilized relative to said surface and fluorescence from molecules immobilized relative to said surface.

13. A method for detecting at least one analyte in a sample, comprising:

applying the sample to a surface of a resonant optical cavity having a quality factor of at least about 10⁴ so as to expose at least one capture substrate immobilized relative to said surface to the at least one analyte;

introducing electromagnetic radiation into said resonant optical cavity; and

detecting binding of the at least one analyte to said at least one capture substrate.

14. A method for detecting at least one analyte in a sample, comprising:

applying the sample to a surface of a resonant optical cavity so as to expose at least one capture substrate immobilized relative to said surface to the at least one analyte;

applying to at least one of a fluorescently labeled analyte and a fluorescently labeled molecule that competes with the at least one analyte for a binding site on said at least one capture substrate to said surface;

introducing electromagnetic radiation into said resonant optical cavity; and

detecting binding of the at least one analyte to said at least one capture substrate.

15. The method of claim 14, wherein said detecting comprises detecting excitation of fluorescent tags by employing at least one of one-photon absorption and two-photon absorption.

16. A method for detecting at least one analyte in a sample comprising:

applying the sample to a surface of a resonant optical cavity so as to expose at least one capture substrate immobilized relative to said surface to the at least one analyte;

introducing electromagnetic radiation into said resonant optical cavity; and

detecting binding of the at least one analyte to said at least one capture substrate, further comprising photo-recycling said electromagnetic radiation by double resonance of sand resonant optical cavity.

17. A method for detecting at least one analyte in a sample, comprising:

applying the sample to a surface of a resonant optical cavity so as to expose at least one capture substrate immobilized relative to said surface to the at least one analyte;

introducing electromagnetic radiation into said resonant optical cavity; and

detecting binding of the at least one analyte to said at least one capture substrate, wherein said detecting comprises mass sensing.

18. The method of claim 17, wherein said mass sensing comprises measuring a refractive index through cavity detuning.

19. A method for detecting at least one analyte in a sample, comprising:

applying the sample to a surface of a resonant optical cavity so as to expose at least one capture substrate immobilized relative to said surface to the at least one analyte;

introducing electromagnetic radiation into said resonant optical cavity; and

detecting binding of the at least one analyte to said at least one capture substrate, wherein said detecting is effected with a concentration of the at least one analyte being at least one of nanomolar or lower and picomolar or lower.

20. A method for fabricating a resonant optical cavity, comprising:

providing a substrate;

fabricating a contrasting layer on said substrate; and

forming a resonant optical cavity over said contrasting layer, said resonant optical cavity having a refractive index of at least about 1.5 times a refractive index of said contrasting layer.

21. The method of claim 20, wherein said providing said substrate comprises providing at least one of glass, quartz, and a semiconductive material.

22. The method of claim 20, wherein said forming said resonant optical cavity comprises;

forming a material layer comprising at least one of silicon oxide and silicon oxynitride over said contrasting layer; and

patterning said material layer to form at least one cylindrical resonant optical cavity therefrom.