Asynchronous fluorescence scan

• US 6,639,668 B1
• Filed: 11/03/2000
• Issued: 10/28/2003
• Est. Priority Date: 11/03/1999
• Status: Expired due to Fees

• Current Assignee: Cercacor Laboratories
• Original Assignee: Argose, Inc.
• Inventors: Trepagnier, Pierre
• Primary Examiner(s): Evans, F. L.
• Assistant Examiner(s): GEISEL, KARA E
• Application Number:
  US09/704,829
• Time in Patent Office: 1,089 Days
• Field of Search: 356/317, 356/318, 356/417, 356/39, 250/458.1, 250/459.1, 250/461.1, 250/461.2
• US Class Current: 356/317
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/441 Skin evaluation, e.g. for skin disorder diagnosis
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

The present invention is directed to asynchronous scanning devices and methods of using asynchronous scanning to acquire fluorescence data from a sample, such as biological tissue, to facilitate diagnosis of the presence or absence of disease or other abnormality in the sample. The present invention is useful for biomedical diagnostics, chemical analysis or other evaluation of the target sample.

Claims

1. A method of analyzing a sample comprising the steps of:

exposing the sample to an excitation radiation having a wavelength, λ

_ex, thereby generating an emission radiation having a wavelength, λ

_em;

scanning the wavelength of the excitation radiation and the wavelength of the emission radiation to collect a spectrum; and

correlating the spectrum to a condition of the sample, wherein said excitation and emission wavelengths are varied according to the formula;

λ

_em=λ

_ex+Δ

λ

, wherein Δ

λ

varies and Δ

λ

>

Δ

λ

_min, wherein Δ

λ

_min is a minimum separation between the excitation wavelength λ

_ex and the emission wavelength λ

_em.

2. The method of claim 1 wherein the sample is tissue.

3. The method of claim 2 wherein the tissue is an animal tissue.

4. The method of claim 3 wherein the tissue skin.

5. The method of claim 4 wherein the skin is human skin.

6. The method of claim 2 wherein the spectrum comprises fluorescence reemitted by the tissue.

7. The method of claim 1 wherein the condition of the sample comprises the presence or absence of disease.

8. The method of claim 1 wherein the condition of the sample comprises the chemical make-up of the sample.

9. The method of claim 1 wherein the condition of the sample comprises the glucose concentration of the sample.

10. The method of claim 1 wherein the sample is a biological fluid.

11. The method of claim 1 wherein the excitation wavelength is between about 260 and 500 nm.

12. The method of claim 1 wherein the emission wavelength is between about 310 and 550 nm.

13. The method of claim 1 wherein the scanning comprises maintaining a varying, non-constant interval between the wavelength of the excitation radiation and the emission radiation during scanning.

14. The method of claim 1 wherein the formula is further defined whereby λ

_em=mλ

_ex+b, where m≠

1, and Δ

λ

=λ

_em−

λ

_ex>

Δ

λ

_min or λ

_em=f(λ

_ex), where f(λ

_ex) represents any simple curved arc, and Δ

λ

=λ

_em−

λ

_ex>

Δ

λ

_min.

15. An apparatus for testing a sample comprising:

means for exposing the sample to an excitation radiation, λ

_ex, thereby generating and emission radiation, λ

_em;

means for scanning the wavelength of the excitation radiation and the wavelength of the emission radiation to produce a spectrum; and

means for correlating the spectrum to a condition of the sample, wherein said excitation and emission wavelengths are varied according to the formula;

λ

_em=λ

_ex+Δ

λ

, and Δ

λ

varies and Δ

λ

>

Δ

λ

_min, wherein Δ

λ

_min is a minimum separation between the excitation wavelength λ

_ex and the emission wavelength λ

_em.

16. The apparatus of claim 15 wherein said means for scanning comprises means for maintaining a varying, non-constant interval between the wavelength of the excitation radiation and the emission radiation during scanning.

17. The apparatus of claim 15 wherein the sample is a tissue.

18. The apparatus of claim 17 wherein the tissue is an animal tissue.

19. The apparatus of claim 18 wherein the tissue is skin.

20. The apparatus of claim 19 wherein the skin is human skin.

21. The apparatus of claim 15 wherein the sample is a biological fluid.

22. The apparatus of claim 15 wherein the spectrum comprises fluorescence re-emitted by the sample.

23. The apparatus of claim 15 wherein the condition of the sample comprises the presence or absence of disease.

24. The apparatus of claim 15 wherein the condition of the sample comprises the chemical make-up of the sample.

25. The apparatus of claim 15 wherein the excitation wavelength is between about 260 and 550 nm.

26. The apparatus of claim 15 wherein the emission wavelength is between about 310 and 550 nm.

27. The apparatus of claim 15 wherein the condition of the sample comprises the glucose concentration of the sample.

28. The method apparatus of claim 15 wherein both the excitation wavelength, λ

_ex, and emission wavelength, λ

_em, are varied, said variation having the mathematical formula λ

_em=mλ

_ex+b, where m≠

1, said variation being subject to the constraint that Δ

λ

=λ

_em−

λ

_ex>

Δ

λ

_min.

29. A fluorescence spectral acquisition system comprising means for exposing a sample to an excitation radiation having an excitation wavelength, λ

_ex, and means for scanning the excitation wavelength and radiation re-emitted by the sample, said radiation having an emission wavelength, λ

_em, wherein both the excitation wavelength, λ

_ex, and emission wavelength, λ

_em, are varied, said variation having the mathematical formula λ

_em=mλ

_ex+b, where m≠

1, said variation being subject to the constraint that Δ

λ

=λ

_em−

λ

_ex>

Δ

λ

_min, wherein Δ

λ

_min is a minimum separation between the excitation wavelength λ

_ex and the emission wavelength λ

_em.

30. The fluorescence spectral acquisition system of claim 29 wherein fluorescent spectral acquisitions are piecewise decomposed into multiple acquisitions.

31. A fluorescence spectral acquisition system comprising means for exposing a sample to an excitation radiation having an excitation wavelength, λ

_ex, and means for scanning the excitation wavelength and radiation re-emitted by the sample, said radiation having an emission wavelength, λ

_em, wherein both the excitation wavelength, λ

_ex, and emission wavelength, λ

_em, are varied, said variation having the mathematical formula λ

_em=f(λ

_ex), where f(λ

_ex) represents any simple curved arc, said variation being subject to the constraint that Δ

λ

=λ

_em−

λ

_ex>

Δ

λ

_min, wherein Δ

λ

_min is a minimum separation between the excitation wavelength λ

_ex and the emission wavelength λ

_em.