Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources

• US 7,626,704 B2
• Filed: 10/26/2007
• Issued: 12/01/2009
• Est. Priority Date: 02/13/2006
• 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, Foquet, Mathieu, Lundquist, Paul, Zaccarin, Denis, Maxham, Mark, Lacroix, Yves
• Primary Examiner(s): Geisel; Kara E
• Application Number:
  US11/978,138
• Publication Number:
  US 20080212960A1
• Time in Patent Office: 767 Days
• Field of Search: 356/417
• US Class Current: 356/417
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/0224 using polarising or depolarising elements
• CPC Class Codes: G01J 3/10 Arrangements of light sources specially adapted for spectrometry or colorimetry
• CPC Class Codes: G01J 3/14 using refracting elements, e.g. prisms G01J3/18, G01J3/26 take precedence prisms per se G02B5/04
• CPC Class Codes: G01J 3/2803 using photoelectric array detector
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 21/6445 Measuring fluorescence polarisation
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• 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 2201/126 Microprocessor processing

Abstract

Methods and systems for real-time monitoring of optical signals from arrays of signal sources, and particularly optical signal sources that have spectrally different signal components. Systems include signal source arrays in optical communication with optical trains that direct excitation radiation to and emitted signals from such arrays and image the signals onto detector arrays, from which such signals may be subjected to additional processing.

Claims

1. A system for monitoring optical signals, comprising:

a substrate having at least a first source of optical signals disposed thereon;

an optical train positioned to receive optical signals from the at least first source of optical signals and image the optical signals onto an imaging detector;

an imaging detector comprising a plurality of pixels, the detector positioned to receive the image of the optical signals on a first set of pixels in the plurality of pixels; and

a processor programmed to process signal data from the detector to monitor the optical signals;

wherein at least one of the detector or processor are configured to process signal data from the first set of pixels in a first data process and data from a second set of pixels in the plurality of pixels different from the first set of pixels in a second data process different from the first data process; and

wherein the first data process comprises subjecting the signal data from the first set of pixels to a gain protocol to amplify the signal data and wherein the second data process does not include subjecting signal data from the second set of pixels to the gain protocol to amplify the signal data.

2. The system of claim 1, wherein the detector comprises a gain register configured to run the gain protocol.

3. The system of claim 1, wherein the second data process does not comprise extracting signal data from the second set of pixels.

4. The system of claim 1, wherein the second data process comprises combining signal data from the second set of pixels with signal data from a plurality of other pixels in the detector upon which signal is not incident to provide combined signal data, and concurrently processing the combined signal data.

5. The system of claim 4, wherein the second data process comprises discarding the combined signal data.

6. The system of claim 1, wherein the substrate comprises a plurality of discrete signal sources disposed thereon.

7. The system of claim 6, wherein each of the plurality of signal sources comprises a fluorescently labeled compound that emits the optical signals in response to an excitation radiation, and wherein the system further comprises a source of excitation radiation positioned to direct excitation radiation at the plurality of signal sources on the substrate.

8. The system of claim 6, wherein the substrate comprises a plurality of reaction wells, each reaction well comprising a complex of a nucleic acid polymerase, a template nucleic acid sequence, a primer sequence and at least one fluorescently labeled nucleotide or nucleotide analog that emits the optical signal in response to activation radiation directed at the reaction well.

9. The system of claim 8, wherein the reaction well comprises a confined illumination region.

10. The system of claim 9, wherein the reaction well comprises a zero mode waveguide.