Integrated analytical system and method

• US 8,994,946 B2
• Filed: 12/21/2012
• Issued: 03/31/2015
• 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: McCaffrey, Nathaniel Joseph, Turner, Stephen, Saxena, Ravi
• Primary Examiner(s): NGUYEN, SANG H
• Application Number:
  US13/725,085
• Publication Number:
  US 20130143206A1
• Time in Patent Office: 830 Days
• Field of Search: 356432-444, 356318-319, 356/417, 385/12, 385/14, 385/123, 385/129, 435/6.1, 435/6.12, 435/287.2, 250/226, 250/214.1, 250/458.1, 250/492.1, 422/82.11
• US Class Current: 356/432
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• 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: C12Q 1/6869 Methods for sequencing
• 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 21/6454 using an integrated detector array
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 2201/064 Stray light conditioning

Abstract

An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.

Claims

1. An analytical device comprising a chip comprising:

an array of zero mode waveguides in a transparent material, each zero mode waveguide having a sample within it, and each zero mode waveguide connected to a fluid conduit for bringing fluid to the zero mode waveguide, the fluid conduit surrounded by an opaque material preventing illumination light from entering the fluid conduit and preventing illumination light from entering a zero mode waveguide from above;

wherein the chip is configured such that the illumination light enters the chip from above and is directed up into the bottom of the zero mode waveguides by reflective optical elements below the zero mode waveguides;

wherein the illumination light stimulates emission from the sample within the zero mode waveguide into the transparent material to a detector below the zero mode waveguide.

2. The analytical device of claim 1 wherein the detector below the zero mode waveguide is built into the chip.

3. The analytical device of claim 1 wherein there are multiple detectors below each zero mode waveguide.

4. The analytical device of claim 3 wherein there are four detectors below each zero mode waveguide, one corresponding to each of four colors.

5. The analytical device of claim 1 wherein the optical elements comprise mirrors or dielectric stacks.

6. The analytical device of claim 1 wherein illumination light from above the chip comprises flood illumination.

7. The analytical device of claim 1 wherein the chip comprises rows of zero mode waveguides separated by transparent regions open to illumination from above.

8. The analytical device of claim 1 wherein the device is used to perform nucleic acid sequencing by polymerase mediated template dependent incorporation of labeled nucleotides.

9. The analytical device of claim 1, wherein the opaque material comprises aluminum.

10. An analysis method comprising:

providing a chip comprising an array of zero mode waveguides within a transparent material, each zero mode waveguide having a sample within it, and each zero mode waveguide connected to a fluid conduit for bringing fluid to the zero mode waveguide, the fluid conduit surrounded by an opaque material preventing illumination light from entering the fluid conduit and preventing illumination light from entering a zero mode waveguide from above;

providing illumination light to the chip from above, whereby the illumination light is directed up into the bottom of the zero mode waveguides by reflective optical elements below the zero mode waveguides;

wherein the illumination light stimulates emission from the sample within the zero mode waveguide into the transparent material; and

detecting the emission from the sample with a detector below the zero mode waveguide.

11. The method of claim 10 wherein the detector below the zero mode waveguide is built into the chip.

12. The method of claim 10 wherein there are multiple detectors below each zero mode waveguide.

13. The analytical device of claim 12 wherein there are four detectors below each zero mode waveguide, one corresponding to each of four colors.

14. The method of claim 10 wherein the optical elements comprise mirrors or dielectric stacks.

15. The method of claim 10 wherein illumination light from above the chip comprises flood illumination.

16. The method of claim 10 wherein the chip comprises rows of zero mode waveguides separated by transparent regions open to illumination from above.

17. The method of claim 10 wherein the device is used to perform nucleic acid sequencing by polymerase mediated template dependent incorporation of labeled nucleotides.

18. A system comprising:

a socket; and

an analytical device held within the socket;

wherein the analytical device comprises a chip, and the chip comprises;

an array of zero mode waveguides in a transparent material, each zero mode waveguide having a sample within it, and each zero mode waveguide connected to a fluid conduit for bringing fluid to the zero mode waveguide, the fluid conduit surrounded by an opaque material preventing illumination light from entering the fluid conduit and preventing illumination light from entering a zero mode waveguide from above;

wherein the chip is configured such that the illumination light enters the chip from above and is directed up into the bottom of the zero mode waveguides by reflective optical elements below the zero mode waveguides;

wherein the illumination light stimulates emission from the sample within the zero mode waveguide into the transparent material to a detector below the zero mode waveguide;

wherein the socket comprises;

fluidic ports that connect to the fluid conduits on the chip;

at least one light source that provide illumination light to the top of the chip; and

input/output ports for sending and receiving electrical signals to the chip.

19. The system of claim 18, further comprising a computer for receiving and analyzing the electrical signals received from the chip.

20. The system of claim 18 wherein the detector below the zero mode waveguide is built into the chip.

21. The system of claim 18 wherein there are multiple detectors for each nanoscale well.

22. The analytical device of claim 21 wherein there are four detectors for each nanoscale well, one corresponding to each of four colors.

23. The system of claim 18 wherein the optical elements comprise mirrors or dielectric stacks.

24. The system of claim 18 wherein illumination light from above the chip comprises flood illumination.

25. The system of claim 18 wherein the chip comprises rows of zero mode waveguides separated by transparent regions open to illumination from above.

26. The system of claim 18 wherein the device is used to perform nucleic acid sequencing by polymerase mediated template dependent incorporation of labeled nucleotides.