Optics collection and detection system and method

• US 9,291,569 B2
• Filed: 03/09/2015
• Issued: 03/22/2016
• 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): Fritchman, Rebecca M
• Application Number:
  US14/642,139
• Publication Number:
  US 20150247800A1
• Time in Patent Office: 379 Days
• Field of Search: 506/38, 422/69, 422/82.07
• 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 21/253 : 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

Optics collection and detection systems are provided for measuring optical signals from an array of optical sources over time. Methods of using the optics collection and detection systems are also described.

Claims

1. A chip for monitoring analytical reactions comprising:

an aperture layer comprising an array of nanoscale apertures, each nanoscale aperture forming a nanoscale well for receiving a fluid including at least two different fluorescent species;

a fluidic layer above the aperture layer and in fluidic contact with the nanoscale wells;

a waveguide layer below the aperture layer and providing illumination light to the nanoscale wells, the waveguide layer comprising an array of waveguides, each waveguide extending across a plurality of nanoscale wells;

a transmission layer below the waveguide layer; and

a detector layer below the transmission layer and comprising a detector,

wherein;

the transmission layer transmits light emitted from the fluorescent species in the nanoscale wells to the detector layer, wherein the aperture layer, the waveguide layer, the transmission layer and the detector layer are integrated such that light emitted from the fluorescent species are transmitted to the detector layer without passing through air or free space, and

the detector receives and detects the emitted light from the nanoscale wells that is transmitted through the transmission layer, wherein for each nanoscale well, the detector has one or two pixels that receive emitted light from such nanoscale well, and wherein each pixel resolves spectra of at least two fluorescent species.

2. The chip of claim 1 further comprising processing circuits to process the electrical signals from the detector.

3. The chip of claim 1 wherein the emitted light from each nanoscale well is directed to a single pixel that resolves the spectra of the at least two fluorescent species.

4. The chip of claim 1 wherein the one or two pixels that receive emitted light from each nanoscale well resolve the spectra of four fluorescent species.

5. The chip of claim 4 wherein the four fluorescent species comprise four differently labeled nucleotides.

6. The chip of claim 1 wherein different fluorescent species are distinguished based on differences in absorption depth.

7. The chip of claim 1 wherein each of the pixels comprises two or more stacked junctions.

8. The chip of claim 7 wherein the stacked junctions are fabricated in CMOS.

9. The chip of claim 8 wherein a sacrificial top layer is utilized to etch a basic detector into a mesa structure.

10. The chip of claim 7 wherein four spectral signatures are distinguished.

11. The chip of claim 10 wherein the four different signatures are distinguished using two stacked depletion regions sharing a common node.

12. The chip of claim 1 wherein each pixel comprises a PIN junction having two or more I-N junctions at different depths.

13. An analysis system comprising:

a socket for holding a chip of claim 1; and

an illumination system that delivers the illumination to the array of waveguides on the chip;

wherein the socket comprises electrical contacts that mate with electrical contacts on the chip, whereby electrical signals from the detector relating to detected emitted light are transmitted off of the chip through the electrical contacts.

14. The system of claim 13 wherein different fluorescent species are distinguished based on differences in absorption depth.

15. The system of claim 13 wherein each pixel comprises two or more stacked junctions.

16. The system of claim 15 wherein the stacked junctions are fabricated in CMOS.

17. The system of claim 15 wherein four different signatures are distinguished using two stacked depletion regions sharing a common node.

18. The system of claim 13 wherein each pixel comprises a PIN junction having two or more I-N junctions at different depths.

19. The chip of claim 13 wherein the emitted light from each nanoscale well is directed to a single pixel that resolves the spectra of four fluorescent species.

20. The chip of claim 19 wherein the four fluorescent species comprise four differently labeled nucleotides.