Methods and systems for monitoring multiple optical signals from a single source

• US 20070036511A1
• Filed: 08/11/2005
• Published: 02/15/2007
• Est. Priority Date: 08/11/2005
• 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, Lundquist, Paul, Zaccarin, Denis
• Granted Patent: US 7,805,081 B2
• Time in Patent Office: Days
• US Class Current: 385/147
• CPC Class Codes: G01J 3/2803 using photoelectric array detector
• CPC Class Codes: G01J 3/36 Investigating two or more bands of a spectrum by separate detectors
• 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

Methods and systems for monitoring a plurality of different optical signals from a single source of such signals, where each such different optical signal is spatially separated from other such signals and directed to different detectors or locations upon a single detector, which direction is generally accomplished through the use of a small numberof optical components and/or manipulations.

Claims

1. A method of detecting optical signals, comprising:

providing a source of at least first and second optical signals wherein the first optical signal comprises a wavelength different from a wavelength of the at least second optical signal;

passing optical signals through an optical train that transmits the first and second optical signals in divergent paths;

receiving the first and second optical signals at different locations on one optical detector.

2. The method of claim 1, wherein the confined source comprises at least a third optical signal, which comprises a wavelength different from a wavelength of the at least first and second optical signals.

3. The method of claim 2, wherein the third optical signal is spatially separated from the first and second optical signals and directed to a third location on the one optical detector different from the first and second locations.

4. The method of claim 3, wherein the confined source comprises at least a fourth optical signal, which comprises a wavelength different from a wavelength of the at least first, second and third optical signals.

5. The method of claim 4, wherein fourth optical signal is spatially separated from the first, second and third optical signals and directed to a fourth location on the one optical detector different from the first, second and third locations.

6. The method of claim 2, wherein the third optical signal is spatially separated from the first and second optical signals and directed to a first location on a second optical detector.

7. The method of claim 2, wherein the at least first and second optical signals are at least partially concurrent.

8. The method of claim 2, wherein the first and second optical signals are not concurrent.

9. The method of claim 2, wherein the source comprises at least first and second fluorescent components that emit the first and second optical signals, respectively.

10. The method of claim 9, wherein the first and second fluorescent components comprise first and second fluorescent labels covalently coupled to at least first and second different nucleotide polyphosphates or nucleotide polyphosphate analogs.

11. The method of claim 10, wherein the source comprises a confined zero mode waveguide.

12. The method of claim 11, wherein source comprises complex of polymerase, template nucleic acid and primer sequence complementary to a portion of template nucleic acid, immobilized within the zero mode waveguide, and wherein first and second optical signals are produced when first and second different nucleotide polyphosphates or nucleotide polyphosphate analogs bearing the first and second fluorescent labels, respectively, are associated with the complex.

13. The method of claim 2, wherein spatially separating the first and second optical signals comprises passing the first and second optical signals through an optical train that directs the first and second optical signals on divergent paths.

14. The method of claim 13, wherein the optical train comprises an optical grating for spatially separating the first and second optical signals.

15. The method of claim 13, wherein the optical train comprises a prism for spatially separating the first and second optical signals.

16. The method of claim 2, further comprising characterizing the first and second optical signals based upon the location on the detector to which they were directed.

17. The method of claim 2, wherein the source comprises an unknown optical signal, the method further comprising characterizing whether the unknown optical signal is the first or second optical signal by a location upon the one detector to which the unknown optical signal is directed.

18. An analytical system, comprising:

a confined reaction region for containing a reaction mixture that produces at least first and second optical signals wherein the first optical signal comprises a wavelength different from a wavelength of the at least second optical signal;

an optical train in optical communication with the confined reaction region, for receiving the first and second optical signals and spatially separating the first and second optical signals and directing them to different locations on an optical detector.

19. The analytical system of claim 18, wherein the optical detector comprises a photodiode array.

20. The analytical system of claim 18, wherein the optical detector comprises a charge coupled device (CCD).

21. The analytical system of claim 18, wherein the optical train comprises an optical grating that spatially separates the first and second optical signals directed therethrough.

22. The analytical system of claim 21, wherein the optical train comprises an optical grating that spatially separates the first, second and third optical signals directed therethrough.

23. The analytical system of claim 22, wherein the optical train comprises an optical grating that spatially separates the first, second, third and fourth optical signals directed therethrough.

24. The analytical system of claim 18, wherein the optical train comprises a first prism that spatially separates the at least first and second optical signals.

25. The analytical system of claim 18, wherein the confined reaction region comprises a well in a multiwell plate.

26. The analytical system of claim 18, wherein confined reaction region comprises a feature on a molecular array.

27. The analytical system of claim 18, wherein the confined reaction region comprises a zero mode waveguide.

28. The analytical system of claim 24, wherein the optical train further comprises at least a second prism in series with the first prism.

29. The analytical system of claim 28, wherein at least one of the first and second prisms is rotatable around an optical axis of the optical train to adjust a dispersion profile of the optical signals passing therethrough.

30. The analytical system of claim 18, further comprising a processor operably coupled to the detector for individually or collectively recording the first and second optical signals incident upon the different locations on the detector and characterizing the first and second optical signals based upon the different location on the detector upon which said optical signals were incident.

31. An analytical system, comprising:

a confined reaction region for containing a reaction mixture that produces at least first and second optical signals wherein the first optical signal comprises a wavelength different from a wavelength of the at least second optical signal;

an optical train in optical communication with the confined reaction region, for receiving the first and second optical signals and spatially separating the first and second optical signals and directing them to different locations on an optical detector, wherein said optical train comprises a replaceable modular optical component that spatially separates the first and second optical signals passing therethrough.

32. The analytical system of claim 31, wherein the replaceable modular component comprises at least a first prism.

33. The analytical system of claim 31, wherein the modular component comprises at least the first prism and a second prism.

34. The analytical system of claim 32, wherein at least one of the first and second prisms are rotatable around an optical axis of the optical train.

35. The analytical system of claim 31, wherein the replaceable modular component comprises an optical grating.

36. The analytical system of claim 31, further comprising a library of a plurality of replaceable modular components, wherein each of the plurality of modular components has a different dispersion profile for different optical signals.

37. A method of detecting optical signals, comprising:

providing a source of at least first and second optical signals wherein the first optical signal comprises an optical characteristic different from an optical characteristic of the at least second optical signal;

passing optical signals through an optical train that transmits the first and second optical signals in divergent paths;

receiving the first and second optical signals at different locations on one optical detector.

38. A method of detecting optical signals, comprising:

providing a source of at least first and second optical signals wherein the first optical signal comprises a wavelength different from a wavelength of the at least second optical signal; and

directing the first and second optical signals to different locations on one optical detector.

39. A method of detecting optical signals, comprising:

providing a source of a plurality of different optical signals, wherein each different optical signal comprises a wavelength different from each other optical signal;

spatially separating the plurality of different optical signals and directing them to discrete locations on one optical detector.

40. A method of detecting optical signals, comprising:

providing a confined source of at least first and second optical signals wherein the first optical signal comprises a wavelength different from a wavelength of the at least second optical signal; and

spatially separating the first and second optical signals and directing the first and second optical signals to first and second different locations on a first optical detector.