Systems and methods for phase measurements

• US 7,557,929 B2
• Filed: 06/18/2004
• Issued: 07/07/2009
• Est. Priority Date: 12/18/2001
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Dasari, Ramachandra R., Wax, Adam, Yang, Changhuei, Popescu, Gabriel, Feld, Michael S., Fang-Yen, Christopher M.
• Primary Examiner(s): Connolly; Patrick J
• Application Number:
  US10/871,610
• Publication Number:
  US 20050105097A1
• Time in Patent Office: 1,845 Days
• Field of Search: 356/479, 356/497, 356484-489
• US Class Current: 356/484
• 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 system for measuring phase of light passing through a portion of a sample, comprising:

a first light source that generates a first signal at a first wavelength;

an interferometer that receives the first signal and generates a second signal including a first pulse and a second pulse separated by a time delay to form a pulse pair;

a first optical path that optically couples the pulse pair from the interferometer with the sample and a second optical path that optically couples the pulse pair from the interferometer with a reference; and

a detector system that measures a first heterodyne signal from a reflected light pulse pair from the sample and a reflected light pulse pair from the reference resulting from interference between the reflected light from the sample and reflected light from the reference, a phase of the first heterodyne signal indicative of a phase of light from the sample relative to a phase of light from the reference.

2. The system of claim 1 wherein the first signal is a low coherence signal.

3. The system of claim 1 wherein the first light source is one of a superluminescent diode and multimode laser diode.

4. The system of claim 1 wherein the interferometer further comprises a first path and a second path, the second path having an acousto-optic modulator.

5. The system of claim 1 further comprising an optical pathway including an optical fiber.

6. The system of claim 1 further comprising a low coherence signal having a bandwidth of at least 5 nm.

7. The system of claim 1 wherein the system comprises a vibration-isolated heterodyne Michelson interferometer operating at a second wavelength.

8. The system of claim 1 wherein the interferometer further comprises a mirror attached to a translation stage to controllably adjust an optical path length difference.

9. The system of claim 1 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.

10. The system of claim 1 wherein the reference comprises a reflective optical surface.

11. The system of claim 1 further comprising a dual beam probe that delivers light onto tissue.

12. The system of claim 1 wherein the interferometer has an optical delay that matches an optical path difference between the first optical path and the second optical path.

13. A method for noncontact optical measurement of a sample having reflecting surfaces, comprising the steps of:

generating a first light signal at a first wavelength with a first light source;

generating a second signal including a first pulse and a second pulse separated by a time delay to form a light pulse pair using the first light signal and a dual-beam interferometer;

the first light signal and optically coupling the light pulse pair to 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 a first reflected light pulse pair from the sample and a second reflected light pulse pair from the reference; and

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

14. The method of claim 13 wherein the first signal is a low coherence signal that is reflected by the sample.

15. The method of claim 13 wherein the first light source is one of a superluminescent diode and multimode laser diode.

16. The method of claim 13 wherein the interferometer further comprises a first path and a second path, the second path having acousto-optic modulators.

17. The method of claim 13 further comprising an optical pathway including an optical fiber.

18. The method of claim 13 wherein the sample is a portion of a nerve cell.

19. The method of claim 13 wherein the interferometer comprises a vibration-isolated heterodyne Michelson interferometer operating at a second wavelength.

20. The method of claim 13 wherein the interferometer further comprises a mirror attached to a translation stage to controllably adjust an optical path length difference.

21. The method of claim 13 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.

22. The method of claim 13 wherein the sample comprises biological tissue.

23. The method of claim 13 further comprising providing a microscope to detect mechanical changes in the sample.

24. The method of claim 23 wherein the sample comprises at least one of a single neuron and cell mono layers.

25. The method of claim 23 wherein the microscope comprises a bifocal microscope.