High-speed, rugged, time-resolved, Raman spectrometer for sensing multiple components of a sample and for diagnostics of pathological skin conditions such as cancer

• US 7,944,555 B2
• Filed: 08/31/2009
• Issued: 05/17/2011
• Est. Priority Date: 06/12/2006
• Status: Active Grant

• Current Assignee: Optical Oncology, Inc.
• Original Assignee: Optical Oncology, Inc.
• Inventors: Claps, Ricardo
• Primary Examiner(s): Geisel; Kara E
• Application Number:
  US12/551,404
• Publication Number:
  US 20100027002A1
• Time in Patent Office: 624 Days
• Field of Search: 356/301
• US Class Current: 356/301
• CPC Class Codes: G01J 2003/123 Indexed discrete filters
• CPC Class Codes: G01J 3/0218 using optical fibers
• CPC Class Codes: G01J 3/0227 using notch filters
• CPC Class Codes: G01J 3/1895 using fiber Bragg gratings or gratings integrated in a waveguide
• CPC Class Codes: G01J 3/26 using multiple reflection, e.g. Fabry-Perot interferometer, variable interference filters
• CPC Class Codes: G01J 3/2889 Rapid scan spectrometers; Time resolved spectrometry
• CPC Class Codes: G01J 3/32 Investigating bands of a spectrum in sequence by a single detector
• CPC Class Codes: G01J 3/44 Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

A new architecture for implementing a time-resolved Raman spectrometer is 2-3 orders of magnitude faster than current systems. In one embodiment, the invention employs a rotating optical switch to time multiplex an input signal through multiple band-pass filters and into a single optical detector which is electrically activated only when the filtered input light pulse is about to impact it.

Time-multiplexing the input signal through multiple optical filters and time-sequencing the optical detector enables the device to detect and analyze 2-3 orders of magnitude faster than current designs. In one embodiment, the system may be employed for the diagnostics of a pathological condition of skin tissue in patients, such as malignant melanoma or other types of skin cancers and abnormal conditions.

Claims

1. A Raman spectroscopy system comprising:

a plurality of light transmission channels;

a time-division multiplexing device for distributing, in a time multiplexed manner, at least one portion of Raman Stokes radiation scattered from a biological tissue sample to each of the plurality of light transmission channels, wherein the Raman Stokes radiation is formed as a result of light impinging on the biological tissue sample;

a light detector for detecting the distributed portion of the Raman Stokes radiation passed by each of said transmission channels, further wherein each of the transmission channels comprises a filter to select a specific wavelength range for each channel;

an analyzing processor for processing a signal from the light detector to detect at least one particular condition of the biological tissue sample.

2. The system of claim 1, further comprising:

a synchronizing circuit for turning on the light detector only when the distributed at least one portion of the Raman Stokes radiation from the time-division multiplexing device is expected at the light detector and otherwise leaving off the light detector.

18. The system of claim 1, wherein the at least one particular condition is melanoma.

3. A Raman spectroscopy system comprising:

a plurality of light sources, wherein each light source produces at least one continuous-wave first signal to be directed at a biological tissue sample;

a time division multiplexing device for transmitting, in a time multiplexed manner, the at least one continuous-wave first signal from each light source to the biological tissue sample wherein Raman Stokes radiation is scattered as a result of the at least one continuous-wave first signal impinging on the biological tissue sample;

a detector responsive to at least one portion of the scattered Raman Stokes radiation for producing a second signal representing at least one particular condition of the biological tissue sample; and

a synchronizing circuit for turning on the detector at the times that the scattered Raman Stokes radiation is expected at the detector.

4. The system as in claim 3 further comprising:

a light transmission channel for transmitting the at least one portion of the Raman Stokes radiation scattered from the biological tissue sample to the detector; and

a narrow pass-band filter in series with the light transmission channel to pass the at least one portion of the Raman Stokes radiation scattered from the biological tissue sample.

5. The system of claim 3 further comprising:

an analyzing processor connected to the detector for processing each second signal from the detector to detect the at least one particular condition of the biological tissue sample.

6. The system of claim 3 wherein the synchronizing circuit synchronizes the turning on of the detector with the arrival at the detector of the at least one portion of the Raman Stokes radiation scattered from the biological tissue sample.

7. The system of claim 3 wherein the synchronizing circuit synchronizes the turning on of the detector with the arrival at the detector of the at least one portion of the Raman Stokes radiation scattered from the biological tissue sample so as to maximize a sensitivity of the system.

8. The system of claim 5 wherein the synchronizing circuit synchronizes the turning on of the detector with the arrival at the detector of the at least one portion of the Raman Stokes radiation scattered from the biological tissue sample so as to reduce a dark count and noise level present at the analyzing processor.

9. The system as in claim 3 wherein the plurality of light sources comprise a plurality of lasers, each laser operating at a different wavelength from the other lasers.

10. The system as in claim 3 wherein the plurality of light sources comprise emission lamps.

11. The system as in claim 10 further comprising:

a plurality of narrow band-pass filters arranged to allow only a portion of the light from each emission lamp to reach the biological tissue sample.

12. The system of claim 10 wherein each emission lamp comprises a lamp containing mercury, xenon, neon or other suitable gas capable of emitting the light.

19. The system of claim 3, wherein the at least one particular condition is melanoma.

20. The system of claim 5, wherein the at least one particular condition is melanoma.

13. A method of implementing a Raman spectroscopy procedure

which comprises:

causing a light to impinge on a biological tissue sample thereby to scatter the light from said sample to produce Raman Stokes radiation;

distributing, in a time sequence manner, at least one portion of the Raman Stokes radiation to each of a plurality of transmission channels so as to cause the at least one portion of the Raman Stokes radiation transmitted by each transmission channels to arrive in a pre-determined time sequence at an optical detector;

synchronizing a process of turning on of the optical detector with the arrival, in the pre-determined sequence, at the optical detector of the at least one portion of the Raman Stokes radiation from each transmission channel; and

analyzing at least one signal from the optical detector to determine at least one particular condition of the biological tissue sample.

14. The method of claim 13, wherein the analyzing step further comprises using a discrete principle component analysis procedure to detect the at least one particular condition of the biological tissue sample, wherein the at least one particular condition is presence of an analyte.

15. The method of claim 14 wherein the at least one particular condition is presence of two or more discrete analytes.

16. The method of claim 13 wherein the distributing step further comprises using a time-division multiplexing device to distribute, in the time sequence manner, the at least one portion of the Raman Stokes radiation to each of a plurality of transmission channels such that two or more particular conditions of the biological tissue sample can be detected in one cycle of rotation of the time-division multiplexing device.

21. The method of claim 13, wherein the at least one particular condition is melanoma.

17. A method of implementing Raman spectroscopy comprising:

producing, from each of a plurality of light sources, at least one continuous-wave first signal to be directed at a biological tissue sample;

transmitting, in a time sequence manner, the at least one continuous-wave first signal from each light source the biological tissue sample, wherein Raman Stokes radiation is scattered as a result of the at least one continuous-wave first signal impinging on the biological tissue sample;

transmitting at least one portion of the Raman Stokes radiation scattered from the biological tissue sample to a detector;

producing at least one second signal at the detector representing at least one particular condition of the biological tissue sample; and

synchronizing a process of turning on of the detector with the arrival at the detector of the at least one portion of the Raman Stokes radiation scattered from the biological tissue sample.

22. The method of claim 17, further comprising a step of analyzing the at least one second signal from the optical detector to determine at least one particular condition of the biological tissue sample.

23. The method of claim 22, wherein the at least one particular condition is melanoma.

24. The method of claim 22, wherein the analyzing step further comprises using a discrete principle component analysis procedure to detect the at least one particular condition of the biological tissue sample, wherein the at least one particular condition is presence of an analyte.

25. The method of claim 24 wherein the at least one particular condition is presence of two or more discrete analytes.

26. The method of claim 17 wherein the transmitting step further comprises using a time-division multiplexing device to transmit, in the time multiplexed manner, the at least one continuous-wave first signal from each light source the biological tissue sample.