Imaging fluorescence or luminescence lifetime

• US 9,968,258 B2
• Filed: 09/12/2012
• Issued: 05/15/2018
• Est. Priority Date: 09/12/2011
• Status: Active Grant

• Current Assignee: Tufts University
• Original Assignee: Tufts University
• Inventors: Guo, Jian, Sonkusale, Sameer
• Primary Examiner(s): Flory, Christopher A
• Application Number:
  US14/344,507
• Publication Number:
  US 20150173621A1
• Time in Patent Office: 2,071 Days
• Field of Search: 600306, 600312, 600321, 600476
• 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

Devices for use in fluorescence or luminescence lifetime imaging include a chip featuring an imaging region that includes a photodetector for receiving optical signals, and a time-to-digital converter for providing 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 a first optical signal corresponding to excitation light from a light source, and a second optical signal corresponding to emitted fluorescence or luminescence from a sample; and

a time-to-digital converter for providing digital phase output based on the first and second optical signals, wherein the digital phase output corresponds to a temporal offset between waveforms corresponding to the excitation light and the emitted fluorescence or luminescence from the sample.

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

3. 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 first and second optical signals and delivers the extracted phase shift to the time-to-digital converter.

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

5. The device of claim 4, 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.

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

7. A microscope comprising:

a lens; and

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

an imaging region comprising a photodetector for receiving a first optical signal corresponding to excitation light from a light source, and a second optical signal corresponding to emitted fluorescence or luminescence from a sample that passes through the lens; and

a time-to-digital converter for providing digital phase output based on the first and second optical signals, wherein the digital phase output corresponds to a temporal offset between waveforms corresponding to the excitation light and the emitted fluorescence or luminescence from the sample.

8. The microscope of claim 7, wherein the microscope is an oxygen sensing microscope that further comprises an arbitrary function generator.

9. The microscope of claim 7, wherein the imaging region comprises an array of photodetectors.

10. The microscope of claim 7, wherein the integrated CMOS chip further comprises a phase extraction circuit that extracts a phase shift from the first and second optical signals and delivers the extracted phase shift to the time-to-digital converter.

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

12. The microscope of claim 11, wherein the time-to-digital converter comprises delay cells and an encoder that scans the delay cells to locate the localized digital phase output.

13. The microscope of claim 7, wherein the CMOS chip has a surface area of about 4 mm by 4 mm.

14. 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 a first optical signal corresponding to excitation light from a light source, and a second optical signal corresponding to emitted fluorescence or luminescence from a sample; and

a time-to-digital converter for providing digital phase output based on the first and second optical signals, wherein the digital phase output corresponds to a temporal offset between waveforms corresponding to the excitation light and the emitted fluorescence or luminescence from the sample; and

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

15. The scanner of claim 14, wherein the scanner is portable.

16. The scanner of claim 15, wherein the scanner is sized and configured to be hand-held.

17. The scanner of claim 14, wherein the imaging region comprises an array of photodetectors.

18. The scanner of claim 14, wherein the integrated CMOS chip further comprises a phase extraction circuit that extracts a phase shift from the first and second optical signals and delivers the extracted phase shift to the time-to-digital converter.

19. The scanner of claim 14, wherein the time-to-digital converter is configured to provide a localized digital phase output.

20. The scanner of claim 19, wherein the time-to-digital converter comprises delay cells and an encoder that scans the delay cells to locate the localized digital phase output.

21. The scanner of claim 14, wherein the CMOS chip has a surface area of about 4 mm by 4 mm.