Time-delay integration in electrophoretic detection systems

• US 7,468,793 B2
• Filed: 12/15/2004
• Issued: 12/23/2008
• Est. Priority Date: 07/25/2001
• Status: Expired due to Term

• Current Assignee: Masaki Fusama
• Original Assignee: Applied Biosystems, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Nordman, Eric S., Shigeura, John S., Reel, Richard T.
• Primary Examiner(s): STAFIRA, MICHAEL PATRICK
• Application Number:
  US11/012,664
• Publication Number:
  US 20050213093A1
• Time in Patent Office: 1,469 Days
• Field of Search: None
• US Class Current: 356/344
• CPC Class Codes: G01N 27/44721 by optical means

Abstract

An apparatus for detecting analytes in a sample is provided. The apparatus includes: one or more channels having a detection zone; one or more irradiation sources disposed for irradiating the detection zone with non-coherent radiation; a detector array disposed for collecting light signals emitted from markers in the detection zone excited by the radiation, the detector array having an output; and a system coupled to the detector array for effecting time delay integration of the charges on the detector array corresponding to the light signals by accumulating the charges before reading the charges at the output of the detector array. Other apparatus and methods for detecting analytes in a sample are also provided.

Claims

1. An apparatus for detecting analytes in a sample, comprising:

one or more channels having a detection zone;

one or more irradiation sources disposed for irradiating the detection zone with radiation;

a detector array disposed for collecting light signals emitted from markers in the detection zone excited by the radiation, the detector array having an output; and

a system coupled to the detector array for effecting time delay integration of charges on the detector array corresponding to the light signals by accumulating the charges before reading the charges at the output of the detector array, the system effecting time delay integration by moving, relative to one another, the detector array and the detection zone such that the detector array tracks light signals emitted from the markers.

2. The apparatus according to claim 1, wherein the system for effecting time delay integration accumulates the charges by at least one of (a) shifting the charges on the detector array, and (b) moving, relative to one another, the detector array and light signals from the detection zone.

3. The apparatus according to claim 1, wherein the one or more irradiation sources comprises one or more light emitting diodes.

4. The apparatus according to claim 1, further comprising modulating optics disposed between the detection zone and the detector array, the modulating optics comprising a relay lens system having a collimating lens and a re-imaging lens.

5. The apparatus according to claim 4, wherein the modulating optics further include a conditioning filter disposed between the one or more irradiation sources and the detection zone.

6. The apparatus according to claim 5, wherein the modulating optics further include a focusing lens disposed between the conditioning filter and the detection zone.

7. The apparatus according to claim 4, wherein the modulating optics further include a transmission grating disposed between the focusing lens and the re-imaging lens.

8. The apparatus according to claim 4, wherein the modulating optics further include a filter disposed between the detection zone and the detector array for filtering through only the light signals.

9. An apparatus for detecting analytes in a sample, comprising:

one or more channels having a detection zone;

one or more irradiation sources disposed for irradiating the detection zone with radiation;

a detector disposed for collecting light signals emitted from markers in the detection zone excited by the radiation, the detector having an output;

modulating optics disposed between the detection zone and the detector; and

a system coupled to the detector for effecting time delay integration of the charges on the detector corresponding to the light signals by accumulating the charges before reading the charges at the output of the detector, the system effecting time delay integration by moving one or more of the detection zone, the modulating optics, and the detector.

10. The apparatus of claim 9, further comprising a re-imaging lens disposed between the detection zone and the detector array for optically inverting an image produced by the light signals before the image is collected by the detector array.

11. An apparatus for detecting analytes, comprising:

a plurality of elongate channels;

a light source;

an excitation-light pathway extending from said light source to said channels;

focusing optics disposed along said excitation-light pathway; and

a charge-coupled device optically coupled to said channels,

wherein said charge-coupled device is configured to operate in time-delay integration mode by moving the charge-coupled device to track an emission signal.

12. The apparatus of claim 11, wherein said channels are defined by capillary tubes or grooved plates.

13. The apparatus of claim 11, further comprising a separation medium supported by said channels.

14. The apparatus of claim 11, including at least four co-extensive channels.

15. The apparatus of claim 11. further comprising modulating optics disposed along an optical path extending between said charge-coupled device and said channels.

16. The apparatus of claim 11, wherein said light source is a light-emitting diode.

17. An apparatus for detecting analytes, comprising:

a plurality of elongate channels;

a detection zone located at one or both of (i) along said channels and (ii) outside of said channels;

a light source and associated focusing optics configured for irradiating at least a portion of said detection zone with light; and

a charge-coupled device optically coupled to said detection zone for collecting light signals emitted from markers in the detection zone excited by the light irradiated by the light source;

wherein said charge-coupled device is configured to operate in time-delay integration mode, the apparatus effecting time delay integration by moving, relative to one another, the charge-coupled device and the detection zone such that the charge coupled device tracks light signals emitted from the markers.

18. The apparatus of claim 17, wherein said detection zone is located along said channels.

19. The apparatus of claim 17, wherein said detection zone is located outside of said channels.

20. The apparatus of claim 17, including at least four co-extensive channels.

21. The apparatus of claim 17, further comprising modulating optics disposed along an optical path extending between said CCD and said detection zone.

22. The apparatus of claim 17, wherein said light source is a light-emitting diode.

23. An apparatus for detecting analytes, comprising:

a plurality of analyte-migration lanes;

a light source;

an excitation-light pathway extending from said light source to said analyte-migration lanes, with said light source being disposed to direct light along said excitation-light pathway;

a charge-coupled device configured to operate in time-delay integration mode and configured to receive light signals from the plurality of analyte-migration lanes; and

a fluorescence-emission pathway optically coupling said analyte-migration lanes and said charge-coupled device;

modulating optics disposed between the plurality of analyte-migration lanes and the charge-coupled device; and

a system coupled to the charge coupled device for effecting time delay integration by moving one or more of the analyte-migration lanes, the modulating optics, and the charge-coupled device.

24. The apparatus of claim 23, including at least four co-extensive analyte-migration lanes.

25. The apparatus of claim 23, further comprising modulating optics disposed along one or both of said excitation-light and fluorescence-emission pathways.

26. The apparatus of claim 23, wherein said light source is a light-emitting diode.

27. An apparatus for detecting analytes in a sample, comprising:

one or more channels including one or more detection zones;

one or more irradiation sources, each irradiation source being capable of irradiating with radiation at least one of the one or more detection zones;

a detector array disposed for collecting light signals emitted from the one or more detection zones by markers excited by the radiation, the detector array being capable of generating one or more output signals; and

a charge-shifting system coupled to the detector array for effecting time delay integration of charges on the detector array which correspond to the light signals, the charge-shifting system being capable of accumulating the charges on the detector array and moving the detector array at a speed substantially synchronized to respective speeds of migration of bands of markers that migrate across the one or more detection zones, to track an emission signal.

28. The apparatus of claim 27, wherein the charge-shifting system is capable of synchronizing prior to the detector array generating the one or more output signals.

29. An apparatus for detecting analytes in a sample, comprising:

a plurality of channels, each channel including one or more detection zones;

one or more irradiation sources, each irradiation source being capable of irradiating with radiation at least one of the one or more detection zones;

a detector array disposed for collecting light signals emitted from the detection zone by markers excited by the radiation, the detector array being capable of generating one or more output signals;

masks to selectively mask the plurality of channels such that light signals from each of the plurality of channels are kept separate from light signals from others of the plurality of channels; and

a system coupled to the detector array for effecting time delay integration of the charges on the detector array which correspond to the light signals by accumulating the charges before reading the charges at the output of the detector array, the system being capable of effecting time delay integration by moving, relative to one another, the detector array and light signals from the detection zone, the system comprising a charge-shifting system capable of shifting accumulated charges corresponding to light signals emitted from the one or more detection zones.

30. The apparatus of claim 29, wherein the detector array comprises a CCD.

31. The apparatus of claim 29, wherein the system for effecting time delay integration moves one or more of the detection zone, the modulating optics, and the detector.

32. The apparatus of claim 29, wherein the charge-shifting system is capable of shifting accumulated charges corresponding to light signals emitted from the one or more detection zones at a speed substantially synchronized to speeds of migration of bands of markers that migrate across the one or more detection zones.