System and method for dynamic chemical imaging

• US 7,046,359 B2
• Filed: 06/30/2004
• Issued: 05/16/2006
• Est. Priority Date: 06/30/2004
• Status: Expired due to Fees

• Current Assignee: Chemimage Corporation
• Original Assignee: Chemimage Corporation
• Inventors: Maier, John, Tuschel, David, Voigt, Thomas C.
• Primary Examiner(s): EVANS, FANNIE L
• Application Number:
  US10/882,082
• Publication Number:
  US 20060001870A1
• Time in Patent Office: 685 Days
• Field of Search: 356/300, 356/301
• US Class Current: 356/301
• CPC Class Codes: G01J 2003/1269 Electrooptic filter
• CPC Class Codes: G01J 3/12 Generating the spectrum; Monochromators
• CPC Class Codes: G01J 3/1256 using acousto-optic tunable filter; acousto-optic elements or systems G02F1/11, G02F1/33
• CPC Class Codes: G01J 3/2823 Imaging spectrometer
• 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 21/3563 for analysing solids; Preparation of samples therefor
• CPC Class Codes: G01N 21/3577 for analysing liquids, e.g. polluted water
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

A system and method for detecting dynamic changes that occur in a sample between a first time interval and a second time interval using a series of at least first and second sequential chemical images of the sample. During the first time interval: (i) the sample is illuminated with a plurality of photons to thereby produce photons scattered or emitted by the sample; (ii) a two-dimensional array of detection elements is used to simultaneously detect scattered or emitted photons in a first predetermined wavelength band from different locations on or within the sample; and (iii) the two-dimensional array of detection elements is thereafter used one or more further times to simultaneously detect scattered or emitted photons in one or more further predetermined wavelength band(s) from different locations on or within the sample. The outputs of the two-dimensional array of detection elements during the first time interval are then combined to generate the first chemical image of the sample. The process is repeated during the second time interval to generate the second chemical image of the sample. Dynamic changes occurring in the sample between the first time interval and the second time interval are detected based on one or more differences between the first and second chemical images.

Claims

1. A method for detecting dynamic changes that occur in a sample between a first time interval and a second time interval using a series of at least first and second sequential chemical images of the sample, wherein the first chemical image corresponds to an image of the sample during a first time interval, and the second chemical image corresponds to an image of the sample at a second time interval after the first time interval, the method comprising:

(a) during the first time interval;

(i) illuminating the sample, along a first optical path, with a plurality of photons to thereby produce photons scattered or emitted by the sample along a second optical path, wherein the first optical path is at an oblique angle with respect to the second optical path;

(ii) using a two-dimensional array of detection elements to simultaneously detect ones of the photons scattered or emitted in step (a)(i) that are within a first predetermined wavelength band from different locations on or within the sample; and

(iii) separately repeating step (a)(ii) for each of a plurality of further different predetermined wavelength bands;

(b) combining the results of steps (a)(ii) and (a)(iii) to generate the first chemical image of the sample;

(c) during the second time interval;

(i) illuminating the sample, along the first optical path, with a plurality of photons to thereby produce photons scattered or emitted by the sample alone the second optical path;

(ii) using the two-dimensional array of detection elements to simultaneously detect ones of the photons scattered or emitted in step (c)(i) that are within the first predetermined wavelength band from different locations on or within the sample; and

(iii) separately repeating step (c)(ii) for each of the plurality of further different predetermined wavelength bands;

(d) combining the results of steps (c)(ii) and (c)(iii) to generate the second chemical image of the sample; and

(e) detecting dynamic changes occurring in the sample between the first time interval and the second time interval based on one or more differences between the first and second chemical images.

2. The method of claim 1, further comprising varying an electric field applied to or within the sample between the first and second time intervals.

3. The method of claim 1, further comprising varying a magnetic field applied to or within the sample between the first and second time intervals.

4. The method of claim 1, further comprising varying an external optical field applied to or within the sample between the first and second time intervals, wherein the external optical field is distinct from an optical field used to illuminate the sample in step (a)(i).

5. The method of claim 1, further comprising varying internally generated photons applied to or within the sample between the first and second time intervals.

6. The method of claim 1, further comprising varying a polarization used to illuminate the sample between the first and second time intervals.

7. The method of claim 1, further comprising varying a temperature of the sample between the first and second time intervals.

8. The method of claim 1, further comprising varying a pressure applied to the sample between the first and second time intervals.

9. The method of claim 1, further comprising varying a stress applied to or within the sample between the first and second time intervals.

10. The method of claim 1, wherein a chemical gradient associated with the sample varies between the first and second time intervals.

11. The method of claim 1, wherein a chemical gradient imposed on the sample varies between the first and second time intervals.

12. The method of claim 1, further comprising inducing a physiological or biological stress in the sample between the first and second time intervals.

13. The method of claim 1, further comprising:

repeating steps (a)(ii) and (a)(iii) for each of a plurality of depths within the sample during the first time interval, wherein the first chemical image of the sample includes a spatially accurate wavelength-resolved chemical image associated with each of the plurality of depths within the sample; and

repeating steps (c)(ii) and (c)(iii) for each of the plurality of depths within the sample during the second time interval, wherein the second chemical image of the sample includes a spatially accurate wavelength-resolved chemical image associated with each of the plurality of depths within the sample.

14. The method of claim 1, wherein step (e) further comprises correlating differences between the first and second chemical images with orthogonal measurements of the sample made during the first and second time intervals, wherein the orthogonal measurements correspond to measurements made using at least one of the following modalities:

Raman scattering, near infrared absorption (NIR), visual imagery, video or luminescence.

15. A method for detecting dynamic changes that occur in a sample between a first time interval and a second time interval using a series of at least first and second sequential chemical images of the sample, wherein the first chemical image corresponds to an image of the sample during a first time interval, and the second chemical image corresponds to an image of the sample at a second time interval after the first time interval, the method comprising:

(a) during the first time interval;

(i) illuminating the sample with a plurality of photons to thereby produce Raman photons scattered by the sample;

(ii) using a two-dimensional array of detection elements to simultaneously detect ones of the Raman photons produced in step (a)(i) that are within a first predetermined wavelength band from different locations on or within the sample; and

(iii) separately repeating step (a)(ii) for each of a plurality of further different predetermined wavelength bands;

(b) combining the results of steps (a)(ii) and (a)(iii) to generate the first chemical image of the sample;

(c) during the second time interval;

(i) illuminating the sample with a plurality of photons to thereby produce Raman photons scattered by the sample;

(ii) using the two-dimensional array of detection elements to simultaneously detect ones of the Raman photons produced in step (c)(i) that are within the first predetermined wavelength band from different locations on or within the sample; and

(iii) separately repeating step (c)(ii) for each of the plurality of further different predetermined wavelength bands;

(d) combining the results of steps (c)(ii) and (c)(iii) to generate the second chemical image of the sample; and

(e) detecting dynamic changes occurring in the sample between the first time interval and the second time interval based on one or more differences between the first and second chemical images.

16. The method of claim 15, further comprising varying an electric field applied to or within the sample between the first and second time intervals.

17. The method of claim 15, further comprising varying a magnetic field applied to or within the sample between the first and second time intervals.

18. The method of claim 15, further comprising varying an external optical field applied to or within the sample between the first and second time intervals, wherein the external optical field is distinct from an optical field used to illuminate the sample in step (a)(i).

19. The method of claim 15, further comprising varying internally generated photons applied to or within the sample between the first and second time intervals.

20. The method of claim 15, further comprising varying a polarization used to illuminate the sample between the first and second time intervals.

21. The method of claim 15, further comprising varying a temperature of the sample between the first and second time intervals.

22. The method of claim 15, further comprising varying a pressure applied to the sample between the first and second time intervals.

23. The method of claim 15, further comprising varying a stress applied to or within the sample between the first and second time intervals.

24. The method of claim 15, wherein a chemical gradient associated with the sample varies between the first and second time intervals.

25. The method of claim 15, wherein a chemical gradient imposed on the sample varies between the first and second time intervals.

26. The method of claim 15, further comprising inducing a physiological or biological stress in the sample between the first and second time intervals.

27. The method of claim 15, further comprising:

repeating steps (a)(ii) and (a)(iii) for each of a plurality of depths within the sample during the first time interval, wherein the first chemical image of the sample includes a spatially accurate wavelength-resolved chemical image associated with each of the plurality of depths within the sample; and

repeating steps (c)(ii) and (c)(iii) for each of the plurality of depths within the sample during the second time interval, wherein the second chemical image of the sample includes a spatially accurate wavelength-resolved chemical image associated with each of the plurality of depths within the sample.

28. The method of claim 15, wherein step (e) further comprises correlating differences between the first and second chemical images with orthogonal measurements of the sample made during the first and second time intervals, wherein the orthogonal measurements correspond to measurements made using at least one of the following modalities:

near infrared absorption (NIR), visual imagery, video or luminescence.