Systems and methods for phase measurements

• US 20050057756A1
• Filed: 04/13/2004
• Published: 03/17/2005
• Est. Priority Date: 12/18/2001
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Wax, Adam, Yang, Changhuei, Popescu, Gabriel, Dasari, Ramachandra R., Feld, Michael S., Fang-Yen, Christopher M.
• Granted Patent: US 7,365,858 B2
• Time in Patent Office: Days
• US Class Current: 356/497
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/7232 involving compression of the physiological signal, e.g. to extend the signal recording period
• CPC Class Codes: G01B 2290/45 Multiple detectors for detecting interferometer signals
• CPC Class Codes: G01B 2290/60 Reference interferometer, i.e. additional interferometer not interacting with object
• CPC Class Codes: G01B 2290/70 Using polarization in the interferometer
• CPC Class Codes: G01B 9/02002 using two or more frequencies
• CPC Class Codes: G01B 9/02007 Two or more frequencies or sources used for interferometric measurement using only beat G01B9/02003
• CPC Class Codes: G01B 9/02011 using temporal polarization variation
• CPC Class Codes: G01B 9/02057 by using common path configuration, i.e. reference and object path almost entirely overlapping
• CPC Class Codes: G01B 9/02063 by particular alignment of focus position, e.g. dynamic focussing in optical coherence tomography
• CPC Class Codes: G01B 9/02067 by electronic control systems, i.e. using feedback acting on optics or light
• CPC Class Codes: G01B 9/02069 Synchronization of light source or manipulator and detector
• CPC Class Codes: G01B 9/02071 by measuring path difference independently from interferometer
• CPC Class Codes: G01B 9/02072 by calibration or testing of interferometer
• CPC Class Codes: G01B 9/02078 Caused by ambiguity
• CPC Class Codes: G01B 9/02083 characterised by particular signal processing and presentation
• CPC Class Codes: G01B 9/0209 Low-coherence interferometers
• CPC Class Codes: G01B 9/02091 Tomographic interferometers, e.g. based on optical coherence
• CPC Class Codes: G01J 9/04 by beating two waves of a same source but of different frequency and measuring the phase shift of the lower frequency obtained
• CPC Class Codes: G01N 21/45 : using interferometric methods; using Schlieren methods

Abstract

Preferred embodiments of the present invention are directed to systems for phase measurement which address the problem of phase noise using combinations of a number of strategies including, but not limited to, common-path interferometry, phase referencing, active stabilization and differential measurement. Embodiment are directed to optical devices for imaging small biological objects with light. These embodiments can be applied to the fields of, for example, cellular physiology and neuroscience. These preferred embodiments are based on principles of phase measurements and imaging technologies. The scientific motivation for using phase measurements and imaging technologies is derived from, for example, cellular biology at the sub-micron level which can include, without limitation, imaging origins of dysplasia, cellular communication, neuronal transmission and implementation of the genetic code. The structure and dynamics of sub-cellular constituents cannot be currently studied in their native state using the existing methods and technologies including, for example, x-ray and neutron scattering. In contrast, light based techniques with nanometer resolution enable the cellular machinery to be studied in its native state. Thus, preferred embodiments of the present invention include systems based on principles of interferometry and/or phase measurements and are used to study cellular physiology. These systems include principles of low coherence interferometry (LCI) using optical interferometers to measure phase, or light scattering spectroscopy (LSS) wherein interference within the cellular components themselves is used, or in the alternative the principles of LCI and LSS can be combined to result in systems of the present invention.

Claims

1. A method for measuring phase of light passing through a portion of a sample comprising the steps of:

providing a first wavelength of light;

directing light of the first wavelength along a first optical path and a second optical path, the first optical path extending onto a sample medium to be measured and the second path undergoing a change in path length; and

detecting light from the sample medium and light from the second optical path to measure a change in phase of light passing through two separate points on the sample medium.

2. The method of claim 1 wherein the medium comprises biological tissue.

3. The method of claim 1 further comprising at least one of a photodiode array and a photodiode-coupled fiber bundle to image the phase of the sample at a plurality of positions simultaneously.

4. The method of claim 1 further comprising the step of frequency shifting the light in the second optical path.

5. The method of claim 1 further comprising the step of detecting the change in phase by at least two photo detectors.

6. The method of claim 1 further comprising providing a helium-neon laser light source that emits the first wavelength.

7. The method of claim 1 further comprising providing a low coherence light source.

22. The method of claim 21, further comprising the step of:

generating a phase image of the sample by repeating the steps of claim 1 for a plurality of points on the sample.

31. The method of claim 22, wherein the step of generating a phase image of the sample comprises generating a phase image of the sample with a phase sensitivity of greater than about λ

/1000.

32. The method of claim 22, wherein the sample comprises a biological tissue.

8. A method for measuring a phase characteristic of light passing through a portion of a sample, comprising the steps of;

providing a first signal and a second signal generated by a first light source and a second light source, respectively, the second light source being a low coherence source;

directing the first signal and the second signal along a first optical path and a second optical path;

varying a path length difference between the first optical path and the second optical path;

generating an output signal indicative of the sum of the first and the second signal with an optical path delay between them;

modulating the output signal at an interferometer lock modulation frequency; and

determining the phase of the sample by the time evolution of the interferometer lock phase.

9. The method of claim 8 wherein the first signal and second signal are low coherence signals.

10. The method of claim 8 further comprising demodulating the first signal by using one of a mixer or lock-in amplifier.

11. The method of claim 8 further comprising electronically generating the interferometer lock phase.

12. A system for measuring phase of light passing through a portion of a sample, comprising:

a first light source that generates a first signal;

an interferometer that generates a second signal with two pulses separated by a time delay from the first signal;

a first optical path from the interferometer in communication with the sample and a second optical path from the interferometer in communication with a reference; and

a detector system that measures a first heterodyne signal from the first and the second signal from the sample and the reference, respectively, and the interference between the light reflected from the sample and the reference; and

detecting a phase of the heterodyne signal indicative of the phase of the sample reflection relative to the reference reflection.

13. The system of claim 12 wherein the first signal is a low coherence signal.

14. The system of claim 12 wherein the first light source is one of a superluminescent diode and multimode laser diode.

15. The system of claim 12 wherein the interferometer further comprises a first path and a second path, the second path having acousto-optic modulators.

16. The system of claim 12 further comprising an optical pathway including an optical fiber.

17. The system of claim 12 further comprising a low coherence signal having a bandwidth of at least 5 nm.

18. The system of claim 12 wherein the system comprises a vibration-isolated heterodyne Michelson interferometer.

19. The system of claim 12 wherein the interferometer further comprises a mirror attached to a translation stage to controllably adjust an optical path length difference.

20. The system of claim 12 wherein the detector system comprises a first detector that detects a signal reflected from the sample and a second detector that detects a signal reflected from the reference.

21. A method for imaging a sample comprising the steps of:

illuminating a sample, the light originating from a point on the sample having a low frequency spatial component and high frequency spatial components;

interfering along a common optical path the high frequency spatial components with the low frequency spatial component to produce a first intensity signal;

shifting the phase of the low frequency spatial component to produce a first phase shifted low frequency spatial component;

interfering along a common optical path the high frequency spatial components with the first phase shifted low frequency spatial component to produce a second intensity signal;

shifting the phase of the low frequency spatial component to produce a second phase shifted low frequency spatial component;

interfering along a common optical path the high frequency spatial components with the second phase shifted low frequency spatial component to produce a third intensity signal;

shifting the phase of the low frequency spatial component to produce a third phase shifted low frequency spatial component;

interfering along a common optical path the high frequency spatial components with the third phase shifted low frequency spatial component to produce a fourth intensity signal;

generating a phase image of the point on the sample based at least in part on the first intensity signal, the second intensity signal, the third intensity signal and the fourth intensity signal.

23. The method of claim 21, wherein the step of illuminating comprises illuminating the sample using a transmission illumination.

24. The method of claim 21, wherein the step of illuminating comprises illuminating the sample using a reflective illumination.

25. The method of claim 21, wherein the step of illuminating comprises illuminating the sample by both transmission and reflective illumination.

26. The method of claim 21, wherein the step of illuminating comprises illuminating the sample with a superluminescent light source.

27. The method of claim 21, further comprising the step of controlling the amplitude of at least one of the high frequency spatial components.

28. The method of claim 21, further comprising the step of controlling the amplitude of at least one of the low frequency spatial component and phase shifted low frequency spatial components.

29. The method of claim 21, wherein each step of shifting the phase shifts the phase of the low frequency spatial component by substantially π

/2.

30. The method of claim 21, wherein the step of generating a phase image is based at least in part on the equation.

33. The method of claim 23, wherein the sample comprises a semiconductor wafer.

34. A method for non-contact optical measurement of a sample having reflecting surfaces, comprising the steps of:

providing a first light source that generates a first signal;

generating a second signal with two pulses separated by a time delay from the first signal using a dual-beam interferometer;

providing a first optical path from the interferometer in communication with the sample and a second optical path from the interferometer in communication with a reference; and

measuring a first heterodyne signal from the first and the second signal from the sample and the reference, respectively, and the interference between the light reflected from the sample and the reference; and

detecting a phase of the heterodyne signal indicative of the phase of the sample reflection relative to the reference reflection.

35. The method of claim 34 wherein the first signal is a low coherence signal.

36. The method of claim 34 wherein the first light source is one of a superluminescent diode and multimode laser diode.

37. The method of claim 34 wherein the interferometer further comprises a first path and a second path, the second path having acousto-optic modulators.

38. The method of claim 34 further comprising an optical pathway including an optical fiber.

39. The method of claim 34 wherein the sample is a portion of a nerve cell.

40. The method of claim 34 wherein the interferometer comprises a vibration-isolated heterodyne Michelson interferometer.

41. The method of claim 34 wherein the interferometer further comprises a mirror attached to a translation stage to controllably adjust an optical path length difference.

42. The method of claim 34 wherein the step of measuring comprises a detector system having a first detector that detects a signal reflected from the sample and a second detector that detects a signal reflected from the reference.

43. The method of claim 34 wherein the sample comprises biological tissue.

44. The method of claim 34 further comprising providing a microscope to detect mechanical changes in the sample.

45. The method of claim 44 wherein the sample comprises at least one of a single neuron and cell monolayers.

46. The method of claim 44 wherein the microscope comprises a bifocal microscope.

47. A fiber optic probe for optically imaging a sample, comprising:

a housing having a proximal end and a distal end;

a fiber collimator in the proximal end of the housing coupled to a light source; and

a graded index lens in the distal end of the housing, the lens having a first and second surface wherein the first surface is the reference surface and wherein numerical aperture of the probe provides efficient light gathering from scattering surfaces of a sample.

48. The probe of claim 47 further comprising a system comprising mounting the fiber optic probe on a translator stage to perform at least one of two-dimensional phase imaging and three-dimensional confocal phase imaging.

49. The probe of claim 48 wherein the translator stage comprises a scanning piezo translator.

50. The probe of claim 47 wherein the numerical aperture of the probe is in a range of approximately 0.4 to 0.5.

51. The probe of claim 47 wherein the probe images in-vivo biological tissue.

52. A method for non-contact optical measurement of an eye, comprising the steps of:

providing a light source that generates a first signal and a second signal;

providing a first optical path from the interferometer in communication with the eye and a second optical path from the interferometer in communication with a reference; and

measuring a first heterodyne signal with light returning from the eye and the reference, respectively, in response to the first signal and the second signal; and

determining a phase of the first heterodyne signal indicative of the phase of the light returning from the eye relative to the light returning from the reference.

53. The method of claim 52 wherein the first signal is a low coherence signal.

54. The method of claim 52 wherein the light source is one of a superluminescent diode and multimode laser diode.

55. The method of claim 52 wherein the interferometer further comprises a first path and a second path, the second path having acousto-optic modulators.

56. The method of claim 52 further comprising an optical pathway including an optical fiber.