Illumination of integrated analytical systems

• US 8,465,699 B2
• Filed: 02/18/2011
• Issued: 06/18/2013
• 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:
  US13/031,103
• Publication Number:
  US 20120014837A1
• Time in Patent Office: 851 Days
• Field of Search: 422/82.11
• US Class Current: 422/82.11
• 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 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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. A device for exciting a fluorophore, said device comprising:

a first region having a reaction cell configured to receive a fluorophore;

a second region laterally adjacent the first region, the second region including a metal-insulator-metal (MIM) structure for providing plasmonic energy to the reaction cell;

a fourth region including an optical waveguide and inlet for receiving optical energy; and

a third region operationally positioned between the second region and the fourth region, the third region including a transition portion at one end of the waveguide adjacent the MIM structure, the transition portion dimensioned and configured to direct the received optical energy to the MIM structure.

2. The device of claim 1 wherein the inlet is positioned along a side edge of the device.

3. The device of claim 1 wherein the waveguide is a planar waveguide.

4. The device of claim 1 wherein the MIM structure and waveguide are essentially concentric rings and the reaction cell is positioned in a center of the ring.

5. A device for exciting a fluorophore, said device comprising:

a metal layer for generating plasmons based on plasmon modes in response to optical energy, the metal layer comprising top and bottom portions;

a dielectric slab extending between the top and bottom portions of the metal layer;

a waveguide disposed between either the top or bottom portion of the metal layer and the dielectric slab, the waveguide configured to receive optical energy and transmit the optical energy to metal-dielectric interfaces to generate the plasmon modes; and

a reaction cell disposed adjacent to the ends of the dielectric slab and metal layer, the reaction cell configured to receive a fluorophore;

wherein the metal layer and slab are in communication with the reaction cell whereby plasmons generated in the metal are transmitted to the reaction cell.

6. The device of claim 5, wherein the reaction cell is defined by an aperture extending upwardly through the metal layer and dielectric slab.

7. The device of claim 6, wherein the waveguide extends around at least a portion of a circumference of the reaction cell, an inner diameter of the waveguide extending inward toward the reaction cell.

8. The device of claim 7, wherein the waveguide and metal layer are ring-shaped and extend entirely around the reaction cell.

9. The device of claim 5, further comprising a sensor element disposed in a substrate below the dielectric slab and metal layer, the sensor element in optical communication with the reaction cell along a detection pathway.

10. The device of claim 9, wherein the sensor element is positioned essentially below the reaction cell.

11. The device of claim 9, further comprising an optically opaque top layer for shielding the reaction cell and the detection pathway.

12. A system comprising:

a planar waveguide layer for receiving light from a light source, wherein the planar waveguide layer comprises a plurality of waveguides;

a plurality of analytical devices according to claim 6 disposed within the planar waveguide layer; and

a set of reactants labeled with a fluorophore for excitation by plasmons in at least one of the reaction cells.