Illumination of integrated analytical systems

• US 9,157,864 B2
• Filed: 05/16/2013
• Issued: 10/13/2015
• Est. Priority Date: 02/19/2010
• Status: Active Grant

• Current Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Original Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Inventors: Fehr, Adrian, McCaffrey, Nathaniel Joseph, Turner, Stephen
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Kingan, Timothy G
• Application Number:
  US13/895,486
• Publication Number:
  US 20130330731A1
• Time in Patent Office: 880 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B82Y 20/00 Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 2021/757 using immobilised reagents
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/64 : Fluorescence; Phosphorescence
• 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 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 21/6456 : Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/648 : using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• 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 21/77 : by observing the effect on a chemical indicator
• CPC Class Codes: G01N 2201/067 : Electro-optic, magneto-optic, acousto-optic elements
• CPC Class Codes: G01N 2201/068 : Optics, miscellaneous
• CPC Class Codes: G01N 2201/08 : Optical fibres; light guides
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G02B 6/1226 : involving surface plasmon interaction
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]

Abstract

An analytical device including an optically opaque cladding, a sequencing layer including a substrate disposed below the cladding, and a waveguide assembly for receiving optical illumination and introducing illumination into the device. The illumination may be received from a top, a side edge, and a bottom of the device. The waveguide assembly may include a nanoscale aperture disposed in the substrate and extending through the cladding. The aperture defines a reaction cell for receiving a set of reactants. In various aspects, the device includes a sensor element and the illumination pathway is through the sensor element. Waveguides and illumination devices, such as plasmonic illumination devices, are also disclosed. Methods for forming and operating the devices are also disclosed.

Claims

1. An analytical device comprising:

a fluidic layer comprising components of an analytical reaction;

a chip comprising an array of nanoscale apertures extending through an opaque layer to a transparent layer below the opaque layer, the nanoscale apertures comprising reaction cells in fluidic communication with the fluidic layer, wherein the reaction cells comprise fluorescent components; and

light deflecting elements below the nanoscale apertures including semitransparent light directing elements which feed light to one or more nanoscale apertures above the semitransparent light directing elements, thereby providing illumination light to the nanoscale apertures,

wherein the nanoscale apertures comprise zero mode waveguides.

2. The analytical device of claim 1

wherein the semitransparent light directing elements are embedded in the transparent layer.

3. The analytical device of claim 1 wherein the semitransparent light directing elements comprise metal or semiconductor mirrors, dichroics, prisms, Bragg scatterers, acousto-optic devices, or electro-optic devices.

4. The analytical device of claim 1 wherein the analytical reaction comprises nucleic acid sequencing, and the fluorescent components comprise fluorescently labeled nucleotides.

5. The analytical device of claim 1 further comprising a gap in the opaque layer providing for the illumination light to pass through the gap to the light deflecting elements.

6. The analytical device of claim 5 wherein the illumination light is directed to the light directing elements by a light pipe.

7. The analytical device of claim 1 wherein the opaque layer comprises a metal.

8. The analytical device of claim 1 further comprising a detector disposed below the nanoscale apertures for detecting light emitted by the fluorescent components.

9. The analytical device of claim 8 further comprising integrated directional optical elements for directing the emitted light to one or more sensor elements on the detector.

10. The analytical device of claim 8 further comprising a filter layer having different filters for multicolor distinction by the detector.

11. The analytical device of claim 1 wherein the device comprises multiple light pipes that allow illumination light to pass through a layer of nanoscale apertures.

12. The analytical device of claim 11 wherein the device comprises between about 100,000 and 1 million nanoscale apertures.

13. A method for monitoring an analytical reaction comprising:

providing an analytical device of claim 8;

providing illumination light to the nanoscale apertures via the light deflection elements; and

detecting light emitted from the fluorescent components, thereby monitoring the analytical reaction.

14. The method of claim 13 wherein the semitransparent light directing elements comprise metal or semiconductor mirrors, dichroics, prisms, Bragg scatterers, acousto-optic devices, or electro-optic devices.

15. The method of claim 13 wherein the analytical reaction comprises nucleic acid sequencing, and the fluorescent components comprise fluorescently labeled nucleotides.

16. The method of claim 13 wherein the analytical device further comprises a gap in the opaque layer providing for illumination light to pass through the gap into the light pipe.

17. An analytical system comprising:

an analytical device of claim 8;

an illumination system providing the illumination light to the light deflection elements; and

a processing system for processing electrical signals from the detector.

18. The analytical system of claim 17 further comprising a fluidic delivery system for delivering fluid to the fluidic layer.

19. The analytical system of claim 17 wherein the semitransparent light directing elements comprise metal or semiconductor mirrors, dichroics, prisms, Bragg scatterers, acousto-optic devices, or electro-optic devices.