Imaging Fluorescence or Luminescence Lifetime

• US 20150173621A1
• Filed: 09/12/2012
• Published: 06/25/2015
• Est. Priority Date: 09/12/2011
• Status: Active Grant

• Current Assignee: Tufts University
• Original Assignee: Tufts University
• Inventors: Guo, Jian, Sonkusale, Sameer
• Granted Patent: US 9,968,258 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/444 Evaluating skin marks, e.g. mole, nevi, tumour, scar
• CPC Class Codes: A61B 5/6801 specially adapted to be attached to or worn on the body surface
• CPC Class Codes: G01J 1/44 Electric circuits for command of an exposure part G03B7/02
• CPC Class Codes: G01J 3/2803 using photoelectric array detector
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: H01L 27/1461 characterised by the photosensitive area

Abstract

Among other things, devices for use in fluorescence or luminescence lifetime imaging are described. The devices include integrated complementary metal-oxide semiconductor (CMOS) chips that include an imaging region and a time-to-digital converter. The imaging region includes a photodetector for receiving optical signals. The time-to-digital converter provides digital phase output based on the received optical signals.

Claims

1. A device for use in fluorescence or luminescence lifetime imaging, the device comprising:

a chip comprising

an imaging region comprising a photodetector for receiving optical signals; and

a time-to-digital converter for providing digital phase output based on the received optical signals.

2. The device of claim 1, wherein the imaging region comprises an array of photodetectors.

6. The device of claim 1, wherein the chip comprises an integrated complementary metal-oxide semiconductor (CMOS) chip, and wherein the CMOS chip further comprises a phase extraction circuit that extracts a phase shift from the received optical signals and delivers the extracted phase shift to the time-to-digital converter.

7. The device of claim 1, wherein the time-to-digital converter is configured to provide a localized digital phase output.

8. The device of claim 7, wherein the time-to-digital converter comprises one or more delay cells and an encoder that scans the delay cells to locate the localized digital phase output.

9. The device of claim 1, wherein the chip has a surface area of about 4 mm by 4 mm.

3-5. -5. (canceled)

10. A microscope comprising:

a lens; and

an integrated complementary metal-oxide semiconductor (CMOS) chip comprising

an imaging region comprising a photodetector for receiving optical signals that pass the lens; and

a time-to-digital converter for providing digital phase output based on the received optical signals.

11. The microscope of claim 10, wherein the microscope is an oxygen sensing microscope that further comprises an arbitrary function generator.

12. The microscope of claim 10, wherein the imaging region comprises an array of photodetectors.

15. The microscope of claim 10, wherein the integrated CMOS chip further comprises a phase extraction circuit that extracts a phase shift from the received optical signals and delivers the extracted phase shift to the time-to-digital converter.

16. The microscope of claim 10, wherein the time-to-digital converter is configured to provide a localized digital phase output.

17. The microscope of claim 16, wherein the time-to-digital converter comprises delay cells and an encoder that scans the delay cells to locate the localized digital phase output.

18. The microscope of claim 10, wherein the CMOS chip has a surface area of about 4 mm by 4 mm.

13-14. -14. (canceled)

19. A scanner for use in detecting skin cancer, the scanner comprising:

an integrated complementary metal-oxide semiconductor (CMOS) chip comprising

an imaging region comprising a photodetector for receiving optical signals; and

a time-to-digital converter for providing digital phase output based on the received optical signals; and

a display for displaying the digital phase output from the integrated CMOS chip.

20. The scanner of claim 19, wherein the skin scanner is portable.

21. The scanner of claim 20, wherein the skin scanner is sized and configured to be hand-held.

22. The scanner of claim 19, wherein the imaging region comprises an array of photodetectors.

25. The scanner of claim 19, wherein the integrated CMOS chip further comprises a phase extraction circuit that extracts a phase shift from the received optical signals and delivers the extracted phase shift to the time-to-digital converter.

26. The scanner of claim 19, wherein the time-to-digital converter is configured to provide a localized digital phase output.

27. The scanner of claim 26, wherein the time-to-digital converter comprises delay cells and an encoder that scans the delay cells to locate the localized digital phase output.

28. The scanner of claim 19, wherein the CMOS chip has a surface area of about 4 mm by 4 mm.

23-24. -24. (canceled)

29. A method for imaging lifetime of fluorescence or luminescence, the method comprising:

receiving optical signals by an imaging region of a chip, wherein the imaging region comprises a photodetector; and

processing the received optical signals to provide a digital phase output from the integrated CMOS chip, wherein processing the received optical signals comprises converting a time delay to the digital phase output by a time-to-digital converter on the CMOS chip.

30. The method of claim 29, further comprising sensing oxygen based on the digital phase output.

31. The method of claim 29, further comprising determining skin cancer based on the digital phase output.

32. The method of claim 29, wherein the optical signals comprise an excitation signal and a fluorescence or luminescence emission signal, and processing the received optical signals comprises extracting a phase difference between the excitation signal and the emission signal.

33. The method of claim 32, wherein processing the received optical signal comprises converting the extracted phase difference within a phase domain into a time delay.

34. (canceled)