Substrates, systems and methods for analyzing materials

• US 7,838,847 B2
• Filed: 10/31/2007
• Issued: 11/23/2010
• Est. Priority Date: 09/01/2006
• Status: Active Grant

• Current Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Original Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Inventors: Turner, Stephen, Lundquist, Paul
• Primary Examiner(s): Porta; David P
• Assistant Examiner(s): Kim; Kiho
• Application Number:
  US11/981,796
• Publication Number:
  US 20080152280A1
• Time in Patent Office: 1,119 Days
• Field of Search: 250/458.1
• US Class Current: 250/458.1
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• 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 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G02B 6/43 Arrangements comprising a plurality of opto-electronic elements and associated optical interconnections

Abstract

Substrates, systems and methods for analyzing materials that include waveguide arrays disposed upon or within the substrate such that evanescent fields emanating from the waveguides illuminate materials disposed upon or proximal to the surface of the substrate, permitting analysis of such materials. The substrates, systems and methods are used in a variety of analytical operations, including, inter alia, nucleic acid analysis, including hybridization and sequencing analyses, cellular analyses and other molecular analyses.

Claims

1. A system for analyzing an analyte, comprising:

a substrate comprising a first surface and at least a first optical waveguide disposed upon the first surface;

at least a first light source optically coupled to the at least first waveguide to direct light into the first waveguide; and

an optical detection system positioned to receive and detect an optical signal from an individual analyte disposed sufficiently proximal to the first surface and external to the waveguide to be illuminated by an evanescent field emanating from the waveguide when light from the light source is passed through the waveguide, wherein the individual analyte is immobilized on the first surface such that a signal from the individual analyte is optically resolvable from any other signal from any other analyte immobilized on the first surface and illuminated by the evanescent field.

2. The system of claim 1, wherein the optical detection system receives and detects signals from a plurality of locations on the surface of the substrate.

3. The system of claim 1, wherein the individual analyte comprises a fluorescent moiety that is excited by light of the wavelength provided by the first light source, and wherein the optical detection system comprises a detector for detecting fluorescent signals, and an optical train positioned to receive fluorescent signals from the first surface of the substrate and direct the fluorescent signals to the detector.

4. The system of claim 1, further comprising at least a second light source optically coupled to the at least first waveguide.

5. The system of claim 1, wherein the substrate comprises an optical switch or modulator disposed thereon for modulating light passing through the waveguide.

6. The system of claim 1, further comprising a mask layer disposed over a first portion of the waveguide, but not over a second portion of the waveguide.

7. The system of claim 6, wherein the second portion of the waveguide comprises at least a first well disposed through the mask layer.

8. The system of claim 6, wherein the second portion of the waveguide comprises a plurality of wells disposed through the mask layer.

9. The system of claim 6, wherein the mask layer is selected from a metal mask layer, a polymeric mask layer, and an inorganic mask layer.

10. The system of claim 9, wherein the mask layer comprises a photoresist layer.

11. The system of claim 9, wherein the mask layer is selected from aluminum, gold, platinum and chrome.

12. The system of claim 9, wherein the mask layer comprises a silica based mask layer.

13. The system of claim 1, wherein the substrate comprises a plurality of waveguides, and an originating waveguide disposed thereon, the originating waveguide being optically coupled to the at least first light source and each of the plurality of waveguides.

14. The system of claim 1, wherein the substrate has a refractive index that is lower than that of the first optical waveguide, and further wherein the first optical waveguide extends into and is at least partially enclosed by the substrate.

15. A system for analyzing an analyte, comprising:

a substrate comprising a first surface and at least a first optical waveguide disposed upon the first surface, wherein the substrate comprises a plurality of optical waveguides disposed upon the first surface of the substrate, and further wherein the plurality of optical waveguides are spaced apart portions of the substrate having a higher refractive index than the substrate has between the plurality of optical waveguides;

at least a first light source optically coupled to the at least first waveguide to direct light into the first waveguide; and

an optical detection system positioned to receive and detect an optical signal from an individual analyte disposed sufficiently proximal to the first surface and external to the waveguide to be illuminated by an evanescent field emanating from the waveguide when light from the light source is passed through the waveguide, wherein the individual analyte is immobilized on the first surface such that a signal from the individual analyte is optically resolvable from any other signal from any other analyte immobilized on the first surface and illuminated by the evanescent field.

16. The system of claim 15, wherein the substrate comprises at least 10 waveguides disposed upon the first surface.

17. The system of claim 16, wherein the substrate comprises a plurality of optical switches or modulators to control light passing through each of the at least 10 waveguides.

18. The system of claim 15, wherein the substrate comprises at least 20 waveguides disposed upon the first surface.

19. The system of claim 15, wherein the substrate comprises at least 40 waveguides disposed upon the first surface.