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

• US 20040069928A1
• Filed: 10/15/2002
• Published: 04/15/2004
• Est. Priority Date: 10/15/2002
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Sagatelyan, Dmitry M., Slettnes, Tor
• Granted Patent: US 6,894,264 B2
• Time in Patent Office: Days
• 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 method for dynamic range extension during the processing of a photo-detector acquired signal, the method comprising:

acquiring a first signal component and a second signal component from a photo-detector wherein the first signal component comprises an integration of the photo-detector signal during a first time interval and wherein the second signal component comprises integration of the photo-detector signal during a second time interval wherein the second time interval is temporally proximal to and shorter than the first time interval such that the second signal component and the first signal component represent the acquired values of the photo-detector signal during a selected time period delineated by the first and second time intervals;

determining a scaling factor between the second signal component and the first signal component;

determining if the first signal component exceeds a selected dynamic range;

if the first signal component exceeds the dynamic range, scaling the second signal component by the scaling factor to approximate the first signal component; and

using the scaled second signal component to represent the value of the signal during the selected time period.

2. The method of claim 1, wherein scaling the second signal component further comprises subtracting an integration independent offset component from the second signal component prior to scaling by the scaling factor.

3. The method of claim 2, wherein the selected time period comprises the second time interval residing substantially adjacent to the first time interval.

4. The method of claim 2, wherein the period comprises a series of long-short-long integration times wherein a short integration time is interposed between two long integration times and wherein the first time interval comprises at least two long integration times, wherein the short and long time intervals share a common median value in time thereby allowing scaling of signals that vary approximately linearly in time.

5. The method of claim 1, wherein the selected time period comprises the first time interval followed by the second time interval.

6. The method of claim 5, wherein an intervening time interval resides between the first and the second time intervals.

7. The method of claim 1, wherein the selected time period comprises substantially the first time interval.

8. The method of claim 7, wherein the second time interval resides substantially within the first time interval.

9. The method of claim 1, wherein the selected time interval comprises the first time interval and the second time interval, each residing substantially adjacent to one another.

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

11. 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 corresponds to a signal acquired during a first interval and wherein the second signal value corresponds to a signal acquired during a second interval, wherein the second signal value is less than the first signal value and wherein the first signal exceeds a specified range;

determining a proportionality parameter K between the first signal value and the second signal value; and

scaling the second signal value to approximate what the first signal value would be beyond the specified range.

12. The method of claim 11, wherein the specified range comprises a dynamic range of a component of the photo-detector signal processor.

13. The method of claim 12, wherein the component of the photo-detector signal processor comprises an analog-to-digital converter.

14. The method of claim 13, further comprising;

determining an offset component for the sample set; and

adjusting the first and second signal values to account for the offset component.

15. The method of claim 14, further comprising assigning a scaled signal value for the sample set based upon the first and second signal values.

16. The method of claim 15, wherein the offset component is subtracted from the first and second signal values.

17. The method of claim 16, wherein the offset component comprises an integration independent signal C.

18. The method of claim 17, wherein the offset C is determined according to the equation C=S−

(L−

S)/(K−

1).

19. The method of claim 18, wherein assigning the scaled signal value for the sample set comprises:

selecting an offset adjusted first signal value to be the scaled signal value if the first signal value is within the specified range;

scaling the offset adjusted second signal value to the first signal value and assigning the scaled offset adjusted second signal value be the scaled signal value for the sample set if the first signal value exceeds the specified range and the unscaled second signal value is within the specified range; and

assigning a default value to the scaled signal value for the sample set if both the first and second signal values exceed the specified range.

20. The method of claim 19, wherein the scaled second signal value is obtained by multiplying the offset C adjusted second signal value by the proportionality parameter K.

21. The method of claim 18, wherein the first interval comprises a long interval and the second interval comprises a short interval substantially adjacent to the long interval.

22. The method of claim 21, 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).

23. The method of claim 21, wherein the first interval comprises a long-short-long component sequence and the second interval comprises the short component of the long-short-long component sequence of the first interval such that the first and second intervals share a common median time value approximately centered about the short interval.

24. The method of claim 23, 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).

25. The method of claim 21, wherein the first interval comprises a long-idle-short-idle-long component sequence and the second interval comprises the short interval of the long-idle-short-idle-long component sequence of the first interval wherein the idle component intervals correspond to dead times.

26. The method of claim 25, wherein the first and second intervals share a common median time value approximately centered about the short interval.

27. The method of claim 26, 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).

28. The method of claim 21, wherein the first interval comprises a long-long component sequence wherein the first signal excludes a short component interposed between the two long components, and wherein the second interval comprises said short component such that the first and second intervals share a common median time value approximately centered about the short interval.

29. The method of claim 28, 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).

30. The method of claim 29, wherein the first signal'"'"'s signal to noise ratio is improved by excluding a noise associated with the photo-detector during the short component wherein the noise includes a shot noise and a read noise.

31. The method of claim 11, 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.

32. The method of claim 11, wherein the photo-detector signal comprises a CCD, a photomultiplier, or a semiconductor based device.

33. A method of sampling a photo-detector signal, the method comprising:

performing a series of integrations of the photo-detector signal wherein the series comprises alternating long and short integration intervals; and

forming a plurality of overlapping sample sets wherein each sample set comprises integrations performed during at least one long interval to yield a first signal value and at least one short interval to yield a second signal value and wherein each sample set overlaps with its neighboring sample set by at least one of the long or short intervals.

34. The method of claim 33, wherein the sample set comprises integrations performed during a sequence of long-short-long time intervals so as to overlap with its neighboring sample set by at least one of the long intervals thereby increasing the number of sample sets obtained from the series of integrations.

35. The method of claim 34, wherein the sample set further comprises idle intervals so as to yield a sequence of long-idle-short-idle-long intervals.

36. The method of claim 33, wherein the first signal value comprises a sum of integrations of the photo-detector signal performed during the long-short-long intervals, and wherein the second signal value comprises the integration of the photo-detector signal performed during the short interval such that the first and second signal values share a common median time value.

37. The method of claim 33, wherein for an approximately linear photo-detector signal, the common median time value of the first and second signal values allow the second signal to be scaled to the first signal value when the first signal value exceeds a specified dynamic range.

38. The method of claim 33, wherein the first signal value comprises a sum of integrations of the photo-detector signal performed during the two long intervals while excluding the short interval, and wherein the second signal value comprises the integration of the photo-detector signal performed during the short interval such that the first and second signal values share a common median time value.

39. The method of claim 33, wherein the first signal'"'"'s signal to noise ratio is improved by excluding a noise associated with the photo-detector during the short component wherein the noise includes a shot noise and a read noise.

40. The method of claim 33, wherein the photo-detector signal comprises a CCD, a photomultiplier, or a semiconductor based device.

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

a photo-detector that detects a labeled sample signal that is transformed 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 interval and wherein the second signal value corresponds to an integrated photo-detector signal acquired during a second interval that is less than the first interval; and

wherein the signal processor is configured to determine a proportionality parameter K between the first signal value and the second signal value such that the second signal value can be scaled to the first signal value and wherein the processor outputs a processed signal representative of the sample set based on the first and second signal values.

42. The system of claim 41, wherein the signal processor further adjusts the first and second signal values to account for identified offset.

43. The system of claim 42, wherein identified offset is subtracted from the first and second signal values.

44. The system of claim 43, wherein the offset comprises an integration independent signal component C determined by the equation C=S−

(L−

S)/(K−

1).

45. The system of claim 44, wherein the processed signal comprises:

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

a scaled second signal value if the first signal value exceeds the dynamic range and the second signal value is within the dynamic range; and

a specified value if both of the first and second signal values exceed the dynamic range.

46. The system of claim 45, wherein the scaled second signal value comprises the offset adjusted second signal value multiplied by the proportionality parameter K.

47. The system of claim 41, wherein the first interval comprises a long interval and the second interval comprises a short interval that is substantially adjacent to the long interval.

48. The system of claim 47, 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).

49. The system of claim 41, wherein the first interval comprises a long-short-long component sequence and the second interval comprises the short component interval of the long-short-long component sequence of the first interval such that the first and second intervals share a common median time value approximately centered about the short interval.

50. The system of claim 46, 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).

51. The system of claim 41, wherein the first interval comprises a long-idle-short-idle-long component sequence and the second interval comprises the short component interval of the long-idle-short-idle-long component sequence of the first interval wherein the idle intervals correspond to dead times associated with the photo-detector and wherein the first and second intervals share a common median time value approximately centered about the short interval.

52. The system of claim 51, 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).

53. The system of claim 41, wherein the first interval comprises a long-long component sequence wherein the first signal is not acquired during a short component interposed between the two long components, and wherein the second interval comprises said short component such that the first and second intervals share a common median time value approximately centered about the short interval.

54. The system of claim 53, 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).

55. The system of claim 54, wherein the first signal'"'"'s signal to noise ratio is improved by excluding a noise associated with the photo-detector during the short component wherein the noise includes a shot noise and a read noise.

56. The system of claim 41, wherein the photo-detector comprises a CCD, a photomultiplier, or a semiconductor based device.

57. The system of claim 41, 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 intervals.