Devices and methods for fluorescent inspection and/or removal of material in a sample

• US 20070269837A1
• Filed: 05/17/2006
• Published: 11/22/2007
• Est. Priority Date: 05/17/2006
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Grissom, Charles B., Jones, Ronald M., McGreevy, James
• Granted Patent: US 8,140,141 B2
• Time in Patent Office: Days
• US Class Current: 435/7.230
• 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 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/417 the bone marrow
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61B 5/7415 Sound rendering of measured values, e.g. by pitch or volume variation A61B5/741 takes precedence
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/82 involving vitamins or their receptors

Abstract

An apparatus is provided that includes a light-emitting component, a light-detecting component, a lock-in amplifier, a frequency generator that is operatively linked to the lock-in amplifier and the light-emitting component, a speaker capable of emitting an audio signal wherein the output audio signal varies depending on the detected fluorescence in the sample, and a visible output of relative fluorescent intensity where the visible output varies depending on the detected fluorescence in the sample. The apparatus may also include a laser that is operatively coupled to the lock-in amplifier through a control switch, and focusing lens or an additional type of filter such as an interference filter, a short-pass filter, a notch filter, a long-pass filter or an infrared filter. The apparatus may be used to identify and/or to remove fluorescent or non-fluorescent material from a sample. Associated methods are also disclosed.

Claims

1. An apparatus for detecting light-emitting material in a sample comprising:

a light-emitting component;

a light-detecting component;

a lock-in amplifier;

a frequency generator operatively coupled to the lock-in amplifier and the light-emitting component;

a sound transducer that is capable of emitting a humanly detectable signal wherein the signal varies with magnitude of detected fluorescence in the sample; and

a visible output of relative fluorescent intensity where the visible output varies with the magnitude of the detected fluorescence in the sample.

2. The apparatus according to claim 1, wherein the light-emitting component is selected form the group consisting of lasers, laser diodes, light-emitting diodes, organic light-emitting diodes, fiber-optic light sources, luminous gas discharges, and hot filament lamps.

3. The apparatus according to claim 1, wherein the light-detecting component is selected form the group consisting of p-n photodiodes, p-i-n photodiodes, photomultiplier tubes, light-sensitive charge coupled devices, and avalanche photodiodes.

4. The apparatus according to claim 1, wherein the visible output of relative fluorescent intensity is selected form the group consisting of LEDs, LCDs, CRTs, plasma, and gauges.

5. The apparatus according to claim 1, further comprising a probe configured to be selectively coupled to the light-emitting component and/or the light-detecting component.

6. The apparatus according to claim 5, wherein the probe is selected from the group consisting of hand-held probes, finger-tip mounted probes, surgical telescopes, endoscopes, cystoscopes, nephroscopes, bronchoscopes, laryngoscopes, otoscopes, arthroscopes, laparoscopes, colonoscopic endoscopes, and gastrointestinal endoscopes.

7. The apparatus according to claim 5, wherein the probe further comprises at least one excitation fiber coupled to the light-emitting component and at least one receiving fiber coupled to the light-detecting component.

8. The apparatus according to claim 5, wherein the probe is sterilizable.

9. The apparatus according to claim 5, wherein the probe is disposable.

24. A method of detecting the location of light-emitting material in a sample, the method comprising:

using the apparatus of claim 1 to detect the location of light-emitting material in a sample.

25. The method according to claim 24, wherein the sample is biological tissue.

26. The method according to claim 25, where the light-emitting material, is located preferentially in cancerous, neoplastic, dysplastic, or hyperplastic tissue.

27. The method according to claim 24, where the light-emitting material is located preferentially in non-cancerous, non-neoplastic, non-dysplastic, or non-hyperplastic tissue.

10. An apparatus for selectively removing or destroying light-emitting or non-light-emitting material in a sample comprising:

a light-emitting component;

a light-detecting component;

a lock-in amplifier;

a frequency generator operatively linked to the lock-in amplifier and the light-emitting component;

an output device configured to remove or destroy a portion of the sample; and

a switch operatively coupled between the lock-in amplifier and the output device to control an output of the output device.

11. The apparatus according to claim 10, wherein the light-emitting component is selected form the group consisting of lasers, laser diodes, light-emitting diodes, organic light-emitting diodes, fiber-optic light sources, luminous gas discharges, and hot filament lamps.

12. The apparatus according to claim 10, wherein the light-detecting component is selected form the group consisting of p-n photodiodes, p-i-n photodiodes, photomultiplier tubes, light-sensitive charge coupled devices, and avalanche photo diodes.

13. The apparatus according to claim 10, further comprising a probe configured to be selectively coupled to the light-emitting component and/or the light-detecting component.

14. The apparatus according to claim 13, wherein the probe is selected from the group consisting of hand-held probes, finger-tip mounted probes, surgical telescopes, endoscopes, cystoscopes, nephroscopes, bronchoscopes, laryngoscopes, otoscopes, arthroscopes, laparoscopes, colonoscopic endoscopes, and gastrointestinal endoscopes.

15. The apparatus according to claim 13, wherein the probe further comprises at least one excitation fiber coupled to the light-emitting component and at least one receiving fiber coupled to the light-detecting component.

16. The apparatus according to claim 13, wherein the probe is sterilizable.

17. The apparatus according to claim 13, wherein the probe is disposable.

18. The apparatus according to claim 10, wherein the output device configured to remove or destroy a portion of the sample is selected from the group consisting of lasers, electrocautery devices or scalpels, and ultrasonic cutters or ablators.

19. The apparatus according to claim 10, wherein the switch activates the output device configured to remove or destroy when an output from the lock-in amplifier rises above a threshold.

20. The apparatus according to claim 19, wherein the threshold is controlled by an operator.

21. The apparatus according to claim 10, wherein the switch activates the output device configured to remove or destroy when an output from the lock-in amplifier falls below a threshold.

22. The apparatus according to claim 21, wherein the optical threshold is controlled by an operator.

23. The apparatus according to claim 10, wherein the output device configured to remove or destroy includes a surgical laser.

28. A method of removing light-emitting material in a sample, the method comprising:

using the apparatus of claim 10 to remove light-emitting material in a sample.

29. The method according to claim 28, wherein the sample is biological tissue.

30. The method according to claim 29, where the light-emitting material is located preferentially in cancerous, neoplastic, dysplastic, or hyperplastic tissue.

31. The method according to claim 29, where the light-emitting material is located preferentially in non-cancerous, non-neoplastic, non-dysplastic, or non-hyperplastic tissue.

32. A method of removing non-light-emitting material in a sample, the method comprising:

using the apparatus of claim 10 to non-remove light-emitting material in a sample.

33. The method according to claim 32, wherein the sample is biological tissue.

34. The method according to claim 32, where the light-emitting material is located preferentially in cancerous, neoplastic, dysplastic, or hyperplastic tissue.

35. The method according to claim 32, where the light-emitting material is located preferentially in non-cancerous, non-neoplastic, non-dysplastic, or non-hyperplastic tissue.

36. A method of removing cancerous, neoplastic, dysplastic, or hyperplastic tissue from a subject, the method comprising:

providing to the subject a light-emitting dye that preferentially localizes to cancerous, neoplastic, dysplastic, or hyperplastic tissue;

detecting the level of fluorescent, phosphorescent, or luminescent intensity in the subject; and

ablating or destroying the tissue in which the relative fluorescent, phosphorescent, or luminescent intensity is detected.