Ocular spectrometer and probe method for non-invasive spectral measurement

• US 20020151774A1
• Filed: 02/28/2002
• Published: 10/17/2002
• Est. Priority Date: 03/01/2001
• Status: Abandoned Application

• Current Assignee: University Of Massachusetts
• Original Assignee: Umass/Worcester
• Inventors: Fiddy, Michael, Saleh, Bilal, Testorf, Markus E., Soller, Babs R., Chaum, Edward
• Application Number:
  US10/086,903
• Publication Number:
  US 20020151774A1
• Time in Patent Office: Days
• US Class Current: 600/318
• CPC Class Codes: A61B 3/1241 specially adapted for observation of ocular blood flow, e.g. by fluorescein angiography
• CPC Class Codes: A61B 3/125 with contact lenses contact lenses per se G02C7/04
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14555 specially adapted for the eye fundus
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

A non-invasive spectral measurement of a native, diagnostic or treatment component in blood or tissue, illuminates the back of the eye and collects return light that has passed through and been reflected from choroidal or retinal tissue. Spectral analysis detects a retinal tissue state, or detects the level of a blood or serum constituent, which may be a native constituent or a dye, marker or pharmacological agent. Time-resolved or spectral decay monitoring may be used to assess organ functioning, e.g., by administering a serum-carried indicator of uptake, clearance or binding rate for specific organs. Circulating cells or material diagnostic of different conditions may also be detected by spectral analysis, either directly, or by tagging with a suitable label. A special probe which may include an ophthalmic lens is arranged to couple the return signal from the fundus into one or more collection fibers coupled to a spectrometer, and may be hand-held or mount directly on the front surface of the cornea, providing a simple clinical tool for non-invasive spectrometric access to the bloodstream, requiring little or no special training, and without resort to costly ophthalmic instrumentation.

Claims

1. A probe for non-invasive spectral assay of a serum-carried component, comprising:

a body having a proximal end, a distal end, and an inner lumen extending therebetween;

a light collection assembly disposed within the inner lumen of the body and being adapted to communicate with an spectrometer for spectral analysis of collected light;

an illumination assembly mated to the body and being effective to provide light; and

an optical assembly mated to the distal end of the body and positionable at the cornea of a subject'"'"'s eye, the optical assembly being configured to direct light from the illumination assembly through a subject'"'"'s eye to tissue and to direct return light from the tissue into the collection assembly.

2. The probe of claim 1, further comprising a processing unit in communication with the collection assembly for analyzing the return light.

3. The probe of claim 1, wherein at least one of the illumination assembly and the light collection assembly is a fiber optic assembly.

4. The probe of claim 1, wherein the light collection assembly comprises at least one collection fiber.

5. The probe of claim 4, wherein the illumination assembly comprises a plurality of illumination fibers.

6. The probe of claim 5, wherein the at least one collection fiber and the plurality of illumination fibers are disposed within the inner lumen of the body, and wherein the plurality of illumination fibers are positioned symmetrically around the at least one collection fiber.

7. The probe of claim 1, further comprising a coupling assembly for slidably moving the collection assembly with respect to optical assembly.

8. The probe of claim 1, wherein the optical assembly includes an ophthalmic lens effective to position the probe on a subject'"'"'s eye and to form an image of the return light.

9. The probe of claim 8, further comprising a collimating lens disposed between the collection assembly and the optical assembly, the collimating lens being effective to focus reflected light from a subject'"'"'s eye to the collection assembly.

10. The probe of claim 1, wherein the tissue comprises choroidal or fundus tissue.

11. The probe of claim 1, wherein the illumination assembly is selected from the group consisting of at least one optical fiber, a miniature light bulb, a surgical light source, and a ophthalmic examination light source.

13. The probe of claim 12, wherein the collection assembly comprises an optical collecting fiber to couple to a spectrometer.

14. The probe of claim 12, wherein the optical assembly includes an ophthalmic lens effective to position the probe on a subject'"'"'s eye.

15. The probe of claim 12, further comprising an illumination assembly for directing light into a subject'"'"'s eye.

16. The probe of claim 15, wherein the body further includes a speculum-shaped projection surface for directing light from the illumination assembly into a subject'"'"'s eye.

17. The probe of claim 12, wherein the optical assembly includes a collimating lens for directing reflected light to the optical collecting fiber.

19. The method of claim 18, wherein said spectrum includes light selected from the group consisting of visible light, ultraviolet (UV), near infrared (NIR), and combinations thereof.

20. The method of claim 18, wherein said structure includes an opthalmic lens and at least one optical fiber, and wherein at least one of the steps of directing and collecting includes coupling light between the fibers and the back of the subject'"'"'s eye.

21. The method of claim 18, wherein the step of processing includes time-resolved processing.

22. The method of claim 21, further comprising the step of administering to the subject an indicator of organ function, and wherein the step of time-resolved processing tracks serum concentration of the indicator thereby assessing organ function.

23. The method of claim 22, wherein the indicator is an indicator taken up by or cleared by an organ.

24. The method of claim 22, wherein the indicator is an indicator selectively taken up by or depleted by a liver or kidney.

25. The method of claim 22, wherein the indicator is an indicator selectively taken up by or depleted by an organism or diseased tissue.

26. The method of claim 18, wherein the step of processing includes correcting the spectrum for a contributing factor.

27. The method of claim 22, wherein the step of time-resolved processing tracks serum concentration of an indicator to assess cardiac function or circulation.

28. The method of claim 27, wherein the step of time-resolved processing tracks serum concentration of a tagged or untagged therapeutic agent.

29. The method of claim 18, wherein said structure is arranged to position illumination and collection light along substantially non-interfering paths through the subject'"'"'s eye so as to reduce scattering noise in the collected light.

30. The method of claim 18, wherein the step of processing includes monitoring a spectral signal of any of a tagged cellular or serum component, a marking agent administered invasively, and a marking agent administered non-invasively.

31. The method of claim 18, wherein the step of directing illumination into the subject'"'"'s eye further comprises the simultaneous step of directing illumination to a reference surface to account for light source fluctuations.

32. The method of claim 18, wherein the step of positioning the optical structure on the front of the subject'"'"'s eye is repeated after the steps of collecting and processing to achieve optimal alignment of the optical structure with the subject'"'"'s eye.

12. A probe for non-invasive spectral assay of a serum-carried component, comprising:

a body;

a light collection assembly disposed within said body, said light collection assembly configured to couple to a spectrometer; and

an optical assembly mated to said body for coupling a return light signal from choroidal or fundus tissue of a subject'"'"'s eye into the light collection assembly, such that the return light signal includes a spectrum of a target component carried in blood or serum;

whereby the spectrometer processes the light signal to directly assay said serum-carried component.

18. A method of performing a non-invasive measurement of a target component present in blood or tissue comprising the steps of:

positioning an optical structure at the front of a subject'"'"'s eye;

directing illumination into the subject'"'"'s eye at fundus tissue;

collecting a light signal returned from said tissue; and

processing a spectrum present in the light signal to measure a targeted serum-carried component present in said tissue.

33. An optical system for non-invasive spectral assay of a serum-carried component, comprising:

a source for providing light;

first and second beam splitters optically coupled to the light source, the first beam splitter directing a portion of the light to a subject'"'"'s eye to elicit reflected light from the eye, and directing a second portion of the light to the second beam splitter;

a reference reflection surface optically coupled to the second beam splitter to be illuminated by the second light portion, said surface directing reflected light in response to said illumination to the second beam splitter; and

first and second collection assemblies coupled to said first and second beam splitters, respectively;

wherein the first beam splitter directs the light reflected from the eye to the first collection assembly, and the second beam splitter directs the light reflected from the reflection surface to said second collection assembly.

34. The optical system of claim 33, further comprising a processor coupled to said first and second collection assemblies, the processor normalizing the reflected light from the subject'"'"'s eye relative to the light reflected from the reference surface to correct for fluctuations in the light emitted by the light source.

35. The optical system of claim 34, wherein the processor normalizes the light reflected from the subject'"'"'s eye in real time.

37. The method of claim 36, wherein the collected light signal is processed to detect a spectrum of a serum-carried component indicative of a health condition or disease state.

38. The method of claim 37, wherein said health condition or disease state is any of non-ophthalmic and ophthalmic disease.

39. The method of claim 37, wherein said targeted serum-carried component is an indicator of disease state.

40. The method of claim 37, wherein said target serum-carried component includes at least one of circulating cells, a marker material, proteins, and peptides.

41. The method of claim 37, wherein the step of processing a spectrum includes monitoring dye kinetics.

42. The method of claim 37, wherein the collected signal includes a visible and/or UV and/or NIR component.

43. The method of claim 37, wherein the collected light includes at least one of a reflectance, a fluorescence and a phosphorescence component.

36. A method of performing a non-invasive measurement of a target component present in the blood or tissue, such as a native, diagnostic or treatment component, wherein the method comprises the steps of:

a) positioning an optical assembly at a front surface of a subject'"'"'s eye to collect a light signal from choroidal tissue at the back of the eye;

b) coupling the collected signal to a spectral processor; and

c) processing a spectrum present in the collected light to directly measure a targeted serum-carried component or a condition present in said tissue.

44. An optical system for non-invasive spectral assay of a serum-carried component, comprising:

a source for providing light;

an optical member coupled to the source for alternatively switching the light propagation direction between a first direction and a second direction, the first direction illuminating a subject'"'"'s eye;

a reference reflectance surface optically coupled to the optical member to be illuminated by light propagating in the second direction, the surface providing reflected light in response to said illumination;

a detector that detects light reflected from the subject'"'"'s eye and the reflectance surface.

45. The optical system of claim 44, wherein the optical member can be any of a chopper, rotating mirror, and a beam-splitter.