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

• US 7,995,202 B2
• Filed: 02/09/2007
• Issued: 08/09/2011
• 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: Maxham, Mark, Turner, Stephen, Foquet, Mathieu, Lundquist, Paul, Zaccarin, Denis, Lacroix, Yves
• Primary Examiner(s): Geisel; Kara E
• Application Number:
  US11/704,689
• Publication Number:
  US 20080030628A1
• Time in Patent Office: 1,642 Days
• Field of Search: 356317-318, 356/417, 2504581-4612
• US Class Current: 356/317
• 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 method of monitoring a plurality of spectrally distinct optical signals from a source of optical signals, comprising:

passing the plurality of optical signals through an optical train that is configured to image each of the plurality of spectrally distinct optical signals onto an imaging detector that comprises a plurality of pixels, wherein an image of each spectrally distinct optical signal produces a shape of an aggregate group of pixels that is characteristic of the optical signal'"'"'s spectral characteristics;

imaging the plurality of optical signals onto the imaging detector; and

identifying each optical signal by the shape of the aggregate group of pixels characteristic of that optical signal.

2. The method of claim 1, wherein the plurality of spectrally distinct optical signals comprises at least two different fluorescently labeled compounds in the source of optical signals, each different fluorescently labeled compound having a different emission spectrum when exposed to excitation radiation.

3. The method of claim 1, wherein the plurality of spectrally distinct optical signals comprises at least four different fluorescently labeled compounds in the source of optical signals, each different fluorescently labeled compound having a different emission spectrum when exposed to excitation radiation.

4. The method of claim 3, wherein the at least four different fluorescently labeled compounds comprise at least four different fluorescently labeled nucleotides, each different nucleotide being labeled with a different fluorescent label having a different emission spectrum.

5. The method of claim 1, wherein the imaging detector is selected from a CCD, an EMCCD, and ICCD, a CMOS sensor, and a hybrid CMOS/CCD sensor.

6. A system for monitoring a plurality of different optical signals from a source of optical signals, comprising:

a substrate having at least a first source of optical signals disposed thereon, the source of optical signals including a plurality of spectrally distinct optical signals;

an optical train positioned to receive the plurality of different optical signals from the at least first source of optical signals and differentially image each of the plurality of different optical signals onto an imaging detector that comprises a plurality of pixels such that each of the different optical signals produces a shape of an aggregate group of pixels that is characteristic of the spectrally distinct optical signal;

the imaging detector that comprises a plurality of pixels; and

a processor for processing signal data from the imaging detector, wherein the processor is configured to identify the spectrally distinct optical signal by the shape of the aggregate group of pixels characteristic of that optical signal.

7. The system of claim 6, wherein the at least first source of optical signals comprises a reaction region having a plurality of different fluorescently labeled compounds disposed therein, each of the different fluorescently labeled compounds having a distinct fluorescent emission spectrum in response to excitation radiation.

8. A method of monitoring a plurality of spectrally different optical signals from a single signal source, comprising:

collecting the spectrally different optical signals in an optical train;

transmitting the spectrally different optical signals through the optical train that is configured to differentially image each of the spectrally different optical signals onto an imaging detector that comprises a plurality of pixels;

differentially imaging each of the spectrally different optical signals onto the imaging detector to produce a shape of an aggregate group of pixels that is characteristic of the optical signal'"'"'s spectral characteristics; and

identifying each spectrally different signal imaged by the shape of the aggregate group of pixels characteristic of that optical signal.