Nonlinear interferometric vibrational imaging

• US 7,623,908 B2
• Filed: 11/19/2003
• Issued: 11/24/2009
• Est. Priority Date: 01/24/2003
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Boppart, Stephen A., Marks, Daniel L.
• Primary Examiner(s): Casler; Brian
• Assistant Examiner(s): LAMPRECHT, JOEL
• Application Number:
  US10/717,437
• Publication Number:
  US 20050168735A1
• Time in Patent Office: 2,197 Days
• Field of Search: 600/407, 600/410, 600/437, 600/476, 600/477, 356/450, 356/451, 356/452, 356/453, 356/456, 356/460
• US Class Current: 600/477
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: G01J 3/44 Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
• CPC Class Codes: G01N 2021/653 Coherent methods [CARS]
• CPC Class Codes: G01N 2021/656 Raman microprobe
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

A method of examining a sample, which includes: exposing a reference to a first set of electromagnetic radiation, to form a second set of electromagnetic radiation scattered from the reference; exposing a sample to a third set of electromagnetic radiation to form a fourth set of electromagnetic radiation scattered from the sample; and interfering the second set of electromagnetic radiation and the fourth set of electromagnetic radiation. The first set and the third set of electromagnetic radiation are generated from a source; at least a portion of the second set of electromagnetic radiation is of a frequency different from that of the first set of electromagnetic radiation; and at least a portion of the fourth set of electromagnetic radiation is of a frequency different from that of the third set of electromagnetic radiation.

Claims

1. A method of examining a sample, comprising:

exposing a non-linear reference medium to a first set of electromagnetic radiation generated in an interferometric system to form a second set of electromagnetic radiation scattered from the non-linear reference medium;

exposing a sample to a third set of electromagnetic radiation to form a fourth set of electromagnetic radiation scattered from the sample; and

interfering the second set of electromagnetic radiation and the fourth set of electromagnetic radiation; and

detecting fourth photos in the fourth set of electromagnetic radiation;

wherein the detecting comprises interfering;

wherein the fourth photons are anti-Stokes photons or Stokes photons;

wherein the first set and the third set of electromagnetic radiation are generated from a source;

at least a portion of the second set of electromagnetic radiation is of a frequency different from that of the first set of electromagnetic radiation; and

at least a portion of the fourth set of electromagnetic radiation is of a frequency different from that of the third set of electromagnetic radiation.

2. The method of claim 1, wherein the fourth photons are anti-Stokes photons.

3. The method of claim 1, wherein the fourth photons are Stokes photons.

6. The method of claim 1, wherein the electromagnetic radiation is in the frequency range of infra-red to ultraviolet light.

8. The method of claim 1, wherein the examining of the sample is by optical coherence tomography.

10. The method of claim 1, wherein the sample is selected from the group consisting of a tissue sample, a single cell, and a patient.

12. The method of claim 10, wherein the sample is a human patient.

4. A method of forming an image of a sample, comprising:

exposing a non-linear reference medium to a first set of electromagnetic radiation generated in an interferometric system to form a second set of electromagnetic radiation scattered from the non-linear reference medium;

exposing a sample to a third set of electromagnetic radiation to form a fourth set of electromagnetic radiation scattered from the sample;

forming a digital data set corresponding to the sample; and

converting the data set into an image;

wherein the forming of the data set comprises interfering the second set of electromagnetic radiation and the fourth set of electromagnetic radiation;

the first set and the third set of electromagnetic radiation are generated from a source;

at least a portion of the second set of electromagnetic radiation is of a frequency different from that of the first set of electromagnetic radiation; and

at least a portion of the fourth set of electromagnetic radiation is of a frequency different from that of the third set of electromagnetic radiation.

5. The method of claim 4, wherein the fourth photons are anti-Stokes photons.

7. The method of claim 4, wherein the electromagnetic radiation is in the frequency range of infra-red to ultraviolet light.

9. The method of claim 4, wherein the forming of the data set is by optical coherence tomography.

11. The method of claim 4, wherein the sample is selected from the group consisting of a tissue sample, a single cell, and a patient.

13. The method of claim 11, wherein the sample is a human patient.

14. In a method of forming an image using an optical coherence tomography, apparatus, the method including exposing a sample or patient to electromagnetic radiation, collecting scattered electromagnetic radiation, and forming an image from the collected electromagnetic radiation including interfering the collected electromagnetic radiation with reference electromagnetic radiation, the improvement comprising the reference electromagnetic radiation being scattered from a non-linear reference sample, and the wavelength of the collected electromagnetic radiation being different from that of the electromagnetic radiation that the sample or patient is exposed to.

15. In an optical coherence tomography device, including an electromagnetic radiation source for generating reference electromagnetic radiation and sample electromagnetic radiation, an optical delay line, a scanner, and a electromagnetic radiation detector, the improvement comprising a reference holder and optics adapted for exposing the reference electromagnetic radiation to a non-linear reference medium before interfering the reference electromagnetic radiation with the sample electromagnetic radiation.

16. A device for examining a sample, comprising:

an oscillator,

a reference generator, including non-linear reference medium, a optically coupled to the oscillator,

a sample illuminator, optically coupled to the oscillator,

an interferometric demodulator, optically coupled to the reference generator and the sample illuminator,

a recorder, coupled to the demodulator, and

a frequency-selecting element that ensures that the light that illuminates the sample is excluded from the modulator.

17. The device of claim 16, wherein the oscillator comprises a laser.

18. The device of claim 17, wherein the oscillator further comprises a pulse shaper or a chirper.

19. The device of claim 16, further comprising a scanner for scanning a sample, coupled to the sample illuminator.

20. A method of examining a sample, comprising:

exposing sample to a first set of electromagnetic radiation generated in an interferometric system to form a second set of electromagnetic radiation non-linearly scattered from the sample; and

interfering the second set of electromagnetic radiation with a third set of electromagnetic radiation;

wherein the third set of electromagnetic radiation is coherent with the first set of electromagnetic radiation;

at least a first portion of the second set of electromagnetic radiation is of a frequency different from that of the first set of electromagnetic radiation; and

at least a portion of the third set of electromagnetic radiation is of the same frequency as the first portion of the second set of electromagnetic radiation.

21. The method of claim 20, further comprising detecting second photons in the second set of electromagnetic radiation;

wherein the detecting comprises the interfering.

22. The method of claim 21, wherein the second photons are anti-Stokes photons.

27. The method of claim 20, wherein the electromagnetic radiation is in the frequency range of infra-red to ultraviolet light.

29. The method of claim 20, wherein the examining of the sample is by optical coherence tomography.

31. The method of claim 20, wherein the sample is selected from the group consisting of a tissue sample, a single cell, and a patient.

33. The method of claim 31, wherein the sample is a human patient.

23. A method of forming an image of a sample, comprising:

exposing a sample to a first set of electromagnetic radiation generated in an interferometric system to form a second set of electromagnetic radiation non-linearly scattered from the sample;

forming a digital data set corresponding to the sample; and

converting the data set into an image;

wherein the forming of the image comprises interfering the second set of electromagnetic radiation and a third set of electromagnetic radiation;

wherein the third set of electromagnetic radiation is phase-coherent with the first set of electromagnetic radiation;

at least a first portion of the second set of electromagnetic radiation is of a frequency different from that of the first set of electromagnetic radiation; and

at least a portion of the third set of electromagnetic radiation is of the same frequency as the first portion of the second set of electromagnetic radiation.

24. The method of claim 23, further comprising detecting second photons in the second set of electromagnetic radiation;

wherein the detecting comprises the interfering, and the forming of the image comprises the detecting.

25. The method of claim 23, wherein the second photons are anti-Stokes photons.

26. The method of claim 23, wherein the second photons are Stokes photons.

28. The method of claim 23, wherein the electromagnetic radiation is in the frequency range of infra-red to ultraviolet light.

30. The method of claim 23, wherein the forming of the image is by optical coherence tomography.

32. The method of claim 23, wherein the sample is selected from the group consisting of a tissue sample, a single cell, and a patient.

34. The method of claim 32, wherein the sample is a human patient.

35. A method of examining a sample, comprising:

exposing a non-linear reference medium to a first set of electromagnetic radiation generated in an interferometric system to form a second set of electromagnetic radiation inelastically scattered from the non-linear reference;

exposing a sample to a third set of electromagnetic radiation to form a fourth set of electromagnetic radiation scattered from the sample; and

interfering the second set of electromagnetic radiation and the fourth set of electromagnetic radiation;

wherein the first set and the third set of electromagnetic radiation are generated from a source;

at least a portion of the second set of electromagnetic radiation is of a frequency different from that of the first set of electromagnetic radiation; and

at least a portion of the fourth set of electromagnetic radiation is of a frequency different from that of the third set of electromagnetic radiation.