System and methods for dynamic range extension using variable length integration time sampling

• US 6,894,264 B2
• Filed: 10/15/2002
• Issued: 05/17/2005
• Est. Priority Date: 10/15/2002
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Sagatelyan, Dmitry M., Slettnes, Tor
• Primary Examiner(s): Luu, Thanh X.
• Assistant Examiner(s): Sohn, Seung C.
• Application Number:
  US10/271,477
• Publication Number:
  US 20040069928A1
• Time in Patent Office: 945 Days
• Field of Search: 250/208.1, 250/214.1, 348307-309, 348311-312, 348/316, 348/317, 348319-323, 377 60- 63
• US Class Current: 250/208.1
• CPC Class Codes: G01J 1/42 using electric radiation detectors optical or mechanical part G01J1/04; by comparison with a reference light or electric value G01J1/10
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2201/1241 Multirange
• CPC Class Codes: H03F 3/08 controlled by light
• CPC Class Codes: H04N 23/70 Circuitry for compensating brightness variation in the scene
• CPC Class Codes: H04N 23/73 by influencing the exposure time
• CPC Class Codes: H04N 23/741 by increasing the dynamic range of the image compared to the dynamic range of the electronic image sensors
• CPC Class Codes: H04N 23/76 by influencing the image signals
• CPC Class Codes: H04N 25/589 with different integration times, e.g. short and long exposures

Abstract

A photo-detector generated signal is measured as a sample set comprising a long signal and a short signal. The short signal is scaled to the value of the long signal if the long signal exceeds a dynamic range associated with the photo detector. In one embodiment, the short signal is obtained during a short time interval that is at the approximate middle of a long time interval such that the short and long intervals share a common median time value. Given such symmetry, an approximately linear signal yields a proportionality parameter between the long and short signals thereby allowing the short signal to be scaled. The proportionality parameter facilitates determination of an integration independent component of the photo detector signal that should be removed from the measured long and short signals before scaling. A plurality of sample sets can also be processed such that each sample set overlaps with its neighboring sample set, thereby increasing the effective number of sample sets.

Claims

1. A system for processing a photo-detector signal associated with a sequencing apparatus, comprising:

a photo-detector that detects a labeled sample signal and transforms said labeled sample signal into an electronic signal;

an electronic signal processor that acquires one or more sample sets associated with the electronic signal wherein each sample set comprises a first signal value L and a second signal value S wherein the first signal value corresponds to an integrated photo-detector signal acquired during a first time interval and wherein the second signal value corresponds to an integrated photo-detector signal acquired during a second time interval that is less than the first time interval; and

wherein the signal processor is configured to determine a proportionality parameter K between the first and second signal values based upon the first and second time intervals, and wherein the signal processor is further configured to determine a signal offset parameter C based upon the first and second signal value and the proportionality parameter and wherein the signal processor determines a signal value representative of the sample set by applying the signal offset parameter and the proportionality parameter to the second signal value if the first signal value exceeds a dynamic range associated with the photo-detector.

2. The system of claim 1, wherein the signal value representative of the sample set is obtained by subtracting the offset parameter from the second signal value and multiplying the resulting value by the proportionality parameter.

3. The system of claim 2, wherein the offset parameter C comprises an integration independent signal value determined by the equation C=S−

(L−

S)/(K−

1).

4. The system of claim 3, wherein the signal representative of the sample set comprises:

the first signal value adjusted by the offset parameter if the first signal value is within the dynamic range associated with the photo-detector; and

a specified cap value if both of the first and second signal values exceed the dynamic range associated with the photo-detector.

5. The system of claim 1, wherein the first time interval comprises a long interval and the second time interval comprises a short interval that is substantially adjacent to the long interval.

6. The system of claim 5, wherein the long interval is longer than the short interval by a factor of approximately n such that for a slow varying photo-detector signal, the proportionality parameter K is approximately equal to n and offset is given by the equation C=S−

(L−

S)/(n−

1).

7. The system of claim 1, wherein the first time interval comprises a long-short-long sequence of intervals and the second time interval comprises the short interval of the long-short-long sequence such that the first and second time intervals share a common median time value approximately centered about the short interval.

8. The system of claim 7, wherein each of the long intervals is longer than the short interval by a factor of approximately n such that for an approximately linear photo-detector signal, the proportionality parameter K is approximated as 2n+1 and the offset is determined according to the equation C=S−

(L−

S)/(2n).

9. The system of claim 1, wherein the first time interval comprises a long-idle-short-idle-long sequence of intervals and the second time interval comprises the short interval of the long-idle-short-idle-long sequence wherein the idle intervals correspond to dead times associated with the photo-detector and wherein the first and second time intervals share a common median time value approximately centered about the short interval.

10. The system of claim 9, wherein each of the long intervals is longer than the short interval by a factor of approximately n such that for an approximately linear photo-detector signal, the proportionality parameter K is approximated as 2n+1 and the offset is determined according to the equation C=S−

(L−

S)/(2n).

11. The system of claim 1, wherein the first time interval comprises a long-long sequence of intervals wherein the first signal value is not acquired during a short interval interposed between the two long intervals, and wherein the second time interval comprises said short interval such that the first and second time intervals share a common median time value approximately centered about the short interval.

12. The system of claim 11, wherein the long interval is longer than the short interval by a factor of approximately n such that for an approximately linear signal, the proportionality parameter K approximately equal to 2 n and offset C is determined according to the equation C=S−

(L−

S)/(2n−

1).

13. The system of claim 12, wherein the first signal'"'"'s signal to noise ratio is improved by excluding a noise associated with the photo-detector during the short interval wherein the noise includes a shot noise and a read noise.

14. The system of claim 1, wherein the photo-detector comprises a CCD, a photomultiplier, or a semiconductor based device.

15. The system of claim 1, wherein the signal processor obtains a plurality of sample sets wherein each sample set overlaps with its neighboring sample set by at least one of the first and second time intervals.

24. The method of claim 1, wherein the photo-detector comprises a CCD, a photomultiplier, or a semiconductor based device.

16. A method for processing a photo-detector acquired signal to extend dynamic range, the method comprising:

identifying first and second signal components of the photo-detector signal wherein the first and second signal components comprise integrations of the photo-detector acquired signal during first and second time intervals that are temporally proximal to one another and of differing durations;

determining if the first or second signal component exceeds a selected dynamic range and generating a scaling value based upon the first and second time intervals for the first or second signal component that do not exceed the selected dynamic range;

determining a signal offset value based upon the first and second signal components and the scaling value for the first or second signal component that does not exceed the selected dynamic range; and

determining a sealed signal value by applying the signal offset value and the scaling value to the first or second signal component that does not exceed the selected dynamic range.

17. The method of claim 16, wherein the first and second time intervals do not overlap temporally.

18. The method of claim 17, wherein the first time interval is followed by the second time interval.

19. The method of claim 18, wherein an intervening time interval temporally resides between the first and the second time intervals.

20. The method of claim 16, wherein the first and second time intervals overlap temporally.

21. The method of claim 20, wherein the the second time interval temporally resides substantially within the first time interval.

22. The method of claim 21, wherein median time values of the first and second time intervals substantially coincide.

23. The method of claim 22, wherein first and second intervening time intervals temporally reside before and after the second time interval, said first and second intervening time intervals also substantially within the first time interval.

25. A method for scaling of a signal generated by a photo-detector signal processor, the method comprising:

determining a first signal value L and a second signal value S for a sample set wherein the first signal value L corresponds to a signal acquired during a first time interval and wherein the second signal value S corresponds to a signal acquired during a second time interval, wherein the second signal value S is less than the first signal value L and wherein the first signal value L exceeds a specified range;

determining a proportionality parameter K between the first and second signal values based upon the first and second time intervals;

determining a signal offset parameter C based upon the first and second signal values L and S and the proportionality parameter K; and

applying the signal offset parameter C to the second signal value and scaling the resulting offset-applied second signal value by the proportionality parameter K to approximate what the offset-applied first signal value would be beyond the specified range.

26. The method of claim 25, wherein the specified range comprises a dynamic range of a component of the photo-detector signal processor.

27. The method of claim 26, wherein the component of the photo-detector signal processor comprises an analog-to-digital converter.

28. The method of claim 25, further comprising assigning the offset and scaled second signal value for the sample set.

29. The method of claim 28, wherein the offset parameter C is subtracted from the second signal values and the resulting offset-applied second signal value is multiplied by the proportionality parameter K.

30. The method of claim 29, wherein the offset parameter C comprises an integration independent value.

31. The method of claim 30, wherein the offset parameter C is determined according to the equation C=S−

(L−

S)/(K−

1).

32. The method of claim 31, further comprising assigning a default value for the sample set if both the first and second signal values L and S exceed the specified range.

33. The method of claim 31, wherein the first time interval comprises a long interval and the second time interval comprises a short interval substantially adjacent to the long interval.

34. The method of claim 33, wherein the long interval is longer than the short interval by a factor of approximately n such that for a slow varying signal, the proportionality parameter K is approximately equal to n and offset C is determined according to the equation C=S−

(L−

S)/(n−

1).

35. The method of claim 33, wherein the first time interval comprises a long-short-long sequence of intervals and the second time interval comprises the short portion of the long-short-long sequence of intervals such that the first and second time intervals share a common median time value approximately centered about the short time interval.

36. The method of claim 35, wherein the long interval is longer than the short interval by a factor of approximately n such that for an approximately linear signal, the proportionality parameter K approximately equal to 2n+1 and offset C is determined according to the equation C=S−

(L−

S)/(2n).

37. The method of claim 33, wherein the first time interval comprises a long-idle-short-idle-long sequence of intervals and the second time interval comprises the short portion of the long-idle-short-idle-long sequence intervals, and wherein the idle portions correspond to dead times.

38. The method of claim 37, wherein the first and second intervals share a common median time value approximately centered about the short interval.

39. The method of claim 38, wherein the long interval is longer than the short interval by a factor of approximately n such that for an approximately linear signal, the proportionality parameter K is approximately equal to 2n+1 and offset is determined according to the equation C=S−

(L−

S)/(2n).

40. The method of claim 33, wherein the first time interval comprises long-long intervals, wherein the first signal value excludes contribution from a short interval interposed between the two long intervals, and wherein the second time interval comprises said short interval such that the first and second time intervals share a common median time value approximately centered about the short time interval.

41. The method of claim 40, wherein the long interval is longer than the short interval by a factor of approximately n such that for an approximately linear signal, the proportionality parameter K approximately equal to 2n and offset C is determined according to the equation C=S−

(L−

S)/(2n−

1).

42. The method of claim 41, wherein the first signal'"'"'s signal to noise ratio is improved by excluding a noise associated with the photo-detector during the short interval wherein the noise includes a shot noise and a read noise.

43. The method of claim 25, further comprising obtaining a plurality of sample sets wherein each sample set overlaps a neighboring sample set by at least one of the first or second intervals.

44. The method of claim 25, wherein the photo-detector signal comprises a CCD, a photomultiplier, or a semiconductor based device.