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

• US 7,630,073 B2
• Filed: 10/26/2007
• Issued: 12/08/2009
• 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: Dixon, John, Turner, Stephen, Lundquist, Paul, Zaccarin, Denis, Lacroix, Yves
• Primary Examiner(s): Geisel; Kara E
• Application Number:
  US11/978,168
• Publication Number:
  US 20080165346A1
• Time in Patent Office: 774 Days
• Field of Search: 356/317
• 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

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. An analytical system, comprising:

a substrate having a plurality of discrete signal sources disposed thereon;

an excitation light source; and

an optical train positioned to transmit excitation light from the excitation light source to the substrate to illuminate a first plurality of illuminated signal sources and a second plurality of illuminated signal sources, and image signals from the plurality of illuminated signal sources onto an array detector;

wherein one or more of the substrate and the optical train are configured such that the first plurality of illuminated signal sources is spaced from the second plurality of illuminated signal sources by a first distance that is greater than a cross sectional dimension of an image of a signal from a signal source in the first plurality of signal sources that is imaged onto the array detector; and

wherein the optical train is configured to provide a first and second illumination profile upon the substrate, wherein the first and second illumination profiles on the substrate are spaced apart by the first distance.

2. The analytical system of claim 1, wherein the first distance is greater than 2 times the cross sectional dimension of the image of a signal from a signal source in the first plurality of signal sources that is imaged onto the array detector.

3. The analytical system of claim 1, wherein the first distance is greater than 3 times the cross sectional dimension of the image of a signal from a signal source in the first plurality of signal sources that is imaged unto the array detector.

4. The analytical system of claim 1, wherein the substrate comprises a first and second plurality of signal sources adjacent to each other on the substrate and separated by the first distance, wherein the first and second plurality of signal sources corresponds to the first and second plurality of illuminated signal sources.

5. The analytical system of claim 4, wherein the first plurality of signal sources comprises a first row of signal sources and the second plurality of signal sources comprises a second row of signal sources, wherein the first and second rows of signal sources are substantially parallel and separated by the first distance.

6. The analytical system of claim 1, wherein the optical train is configured to separately image resolvable signal components from each discrete signal source onto the detector array, wherein images of signal components from a first signal source do not overlap with images from signal components of a second signal source in the plurality of discrete signal sources.

7. The analytical system of claim 6, wherein the resolvable signal components comprise at least 3 resolvable signal components.

8. The analytical system of claim 6, wherein the optical train is configured to image each of the resolvable signal components from a discrete signal source at different adjacent spatially discrete locations on the detector array.

9. The analytical system of claim 6, wherein the resolvable signal components comprise fluorescent emissions having resolvably different spectra.

10. An analytical system, comprising:

a substrate having a plurality of signal sources disposed thereon;

an excitation light source;

an optical train configured to;

receive excitation light from the excitation light source;

direct the excitation light onto the substrate in at least first and second substantially parallel linear illumination profiles, wherein the first and second linear illumination profiles are spaced apart on the substrate by a distance that is greater than a width of the first linear illumination profile; and

receive optical signals from the substrate and image the optical signals onto a detector array.

11. The analytical system of claim 10, wherein the optical train comprises one or more of a cylindrical lens and a holographic optical element for converting excitation light to a linear illumination profile.

12. The analytical system of claim 10, wherein the optical train is configured to direct excitation light at the substrate in at least 4 substantially parallel linear illumination profiles.

13. The analytical system of claim 10, wherein the optical train is configured to direct excitation light at the substrate in at least 10 substantially parallel linear illumination profiles.

14. The analytical system of claim 10, wherein the optical train is configured to direct excitation light at the substrate in at least 20 substantially parallel linear illumination profiles.

15. The analytical system of claim 10, wherein the optical train is configured to direct excitation light at the substrate in at least 50 substantially parallel linear illumination profiles.

16. The analytical system of claim 10, wherein the first and second linear illumination profiles are spaced apart on the substrate by a distance that is at least two times greater than a width of the first linear illumination profile.

17. The analytical system of claim 10, wherein the first and second linear illumination profiles are spaced apart on the substrate by a distance that is at least three times greater than a width of the first linear illumination profile.

18. The analytical system of claim 10, wherein the first and second linear illumination profiles are spaced apart on the substrate by a distance that is at least four times greater than a width of the first linear illumination profile.

19. An analytical system, comprising:

a substrate comprising a plurality of discrete signal sources disposed thereon, wherein at least a first subset of signal sources are positioned in a first substantial linear orientation, and a second subset of signal sources are positioned in a second substantially linear orientation that is substantially parallel to the first linear orientation;

a light source;

an optical train for directing light from the light source to the substrate in at least first and second substantially parallel linear illumination profiles, the first linear profile illuminating the first subset of signal sources and the second illumination profile illuminating the second subset of signal sources.

20. The analytical system of claim 19, wherein a position of the first linear illumination profile on the substrate is independently adjustable from a position of the second linear illumination profile on the substrate.

21. The analytical system of claim 19, wherein the optical train comprises at least a first polarizing beam splitter for dividing light from the light source into at least First and second beams, and linearization optics for converting the first and second beams to the first and second linear illumination profiles on the substrate.

22. A system, comprising:

a substrate comprising a plurality of discrete signal sources;

an excitation light source; and

an optical train, positioned to receive excitation light from the excitation light source and direct the excitation light to the substrate, wherein the optical train is configured to direct the excitation light in at least first and second illumination profiles at a plurality of signal sources, simultaneously, and simultaneously receive optical signals from the plurality of signal sources and direct the optical signals upon an imaging detector, to detect the optical signals from the plurality of signal sources,

wherein the first and second illumination profiles are spaced apart on the substrate by a distance that is greater than a width of the first illumination profile.

23. A system, comprising:

a substrate having at least first and second rows of signal sources disposed thereon;

an excitation light source; and

an optical train, positioned to receive excitation light from the excitation light source and direct the excitation light to the substrate, wherein the optical train is configured to divide the excitation light into at least first and second discrete beams, and direct each of the at least first and second discrete beams in a substantially linear illumination profile at the substrate, wherein the first beam simultaneously illuminates a plurality of signal sources in the first row of signal sources, and the second beam simultaneously illuminates a plurality of signal sources in the second row of signal sources.