Optical assay system for intraoperative assessment of tumor margins

• US 7,952,704 B2
• Filed: 07/02/2010
• Issued: 05/31/2011
• Est. Priority Date: 03/30/2006
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Wilke, Lee G., Ramanujam, Nirmala
• Primary Examiner(s): NGUYEN, SANG H
• Application Number:
  US12/830,078
• Publication Number:
  US 20100301229A1
• Time in Patent Office: 333 Days
• Field of Search: 356/244, 356/246, 356 36- 39, 356/445, 356/344, 250/458.1, 250/492.1, 422/67, 422/82, 422/86, 436/172, 382/128, 382/132, 382/140, 600/310, 600/316
• US Class Current: 356/244
• CPC Class Codes: G01N 21/4738 Diffuse reflection precedence is given to G01N21/55 - G01N21/57 if specular component is taken into consideration, e.g. also for testing fluids, fibrous materials

Abstract

The subject matter described herein includes an optical assay system for intraoperative assessment of tumor margins. According to one aspect, the subject matter described herein includes a biological sample containment and illumination apparatus for holding a biological sample for illumination by a plurality of electromagnetic radiation probes. The biological sample containment and illumination apparatus includes a plurality of frame members positioned with respect to each other to form an interior space for receiving a biological sample. At least one of the plurality of frame members includes a plurality of probe receiving locations for receiving a plurality of electromagnetic radiation probes. The probe receiving locations position the probes with respect to the biological sample to allow illumination of plural locations of the biological sample by the probes.

Claims

1. A method for testing a biological sample, the method comprising:

placing a biological sample in an interior space defined by a biological sample containment and illumination apparatus having a plurality of frame members positioned with respect to each other to form a single interior volume container for holding a biological sample in an interior region defined by the container, at least one of which includes a plurality of probe receiving locations for receiving a plurality of electromagnetic radiation probes and for positioning the probes with respect to the biological sample while the biological sample is located in the interior region defined by the container to allow simultaneous illumination of plural locations of the biological sample by the probes, and further wherein at least one of the plurality of frame members is translatable with respect to another frame member such that the volume of the interior region can be altered in at least one direction and the at least one translatable frame member can be translated to vary the volume of the interior region so that the biological sample can be placed proximal to the plurality of probes;

illuminating the biological sample through the probe receiving locations using the probes; and

detecting electromagnetic radiation reflected from or emitted by the biological sample in response to the illumination.

2. The method of claim 1, wherein at least one of the plurality of frame members is translatable with respect to another frame member such that the volume of interior region can be altered in at least one direction.

3. The method of claim 2, comprising translating the at least one frame member to vary the volume of the interior region so that the sample can be placed proximal to the plurality of probes.

4. The method of claim 2, wherein at least two of the plurality of frame members are translatable in order to alter the volume of the interior region in at least two directions.

5. The method of claim 1, wherein the probe receiving locations are adapted to receive fiber optic probes and wherein the electromagnetic radiation probes comprise fiber optic probes.

6. The method of claim 5, wherein the probe receiving locations comprise a plurality of apertures for receiving the fiber optic probes.

7. The method of claim 6, comprising controlling advancement of each fiber optic probe in each aperture to position the fiber optic probe adjacent to the biological sample.

8. The method of claim 7, wherein controlling advancement of each fiber optic probe in each aperture comprises forming a barrier in a position adjacent proximal to the interior region to prevent the fiber optic probes from entering the interior region.

9. The method of claim 7 wherein controlling advancement of each fiber optic probe comprises coupling an adapter to one of the fiber optic probes and one of the apertures, wherein the adapter limits advancement of the one fiber optic probe in the one aperture.

10. The method of claim 9, comprising bundling the fiber optic probes together such that the adapter that limits the advancement of the one fiber optic probe limits advancement of the remaining bundled fiber optic probes in their respective apertures.

11. The method of claim 5, wherein the fiber optic probes have a sensing depth of between about 1 and 2 mm.

12. The method of claim 5, wherein each of the fiber optic probes has a geometry comprising a central core comprising a plurality of illumination fibers surrounded by at least one concentric ring comprising a plurality of collection fibers.

13. The method of claim 1, wherein the frame members form a parallelepiped structure.

14. The method of claim 13, wherein the parallelepiped structure is a rectangular parallelepiped.

15. The method of claim 1, wherein the frame members are translucent or transparent.

16. The method of claim 1, wherein the probe receiving locations are spaced from each other so as to avoid cross-talk between adjacent probes.

17. The method of claim 16, wherein each of the apertures has a diameter of about 3.7 mm and adjacent apertures have a 2 mm radial separation.

18. The method of claim 1 wherein illuminating the biological sample includes illuminating plural locations on the biological sample in parallel through different probe receiving locations.

19. A system for imaging a sample, the system comprising:

a biological sample containment and illumination apparatus for holding a biological sample for illumination by a plurality of electromagnetic radiation probes, the biological containment and illumination apparatus comprising a plurality of frame members positioned with respect to each other to form a single interior volume container for holding a biological sample in an interior region defined by the container, wherein at least one of the plurality of frame members includes a plurality of probe receiving locations for receiving a plurality of electromagnetic radiation probes and for positioning the probes with respect to the biological sample while the biological sample is located in the interior region defined by the container to allow simultaneous illumination of plural locations of the biological sample by the probes, and further wherein at least one of the plurality of frame members is translatable with respect to another frame member such that the volume of the interior region can be altered in at least one direction and the at least one translatable frame member can be translated to vary the volume of the interior region so that the biological sample can be placed proximal to the plurality of probes;

a plurality of electromagnetic radiation probes for illuminating the plural locations of the biological sample via the probe receiving locations with electromagnetic radiation generated by an electromagnetic radiation source and for detecting electromagnetic radiation reflected from or emitted by the biological sample via the probe receiving locations;

a detector coupled to the probes for receiving electromagnetic radiation signals indicative of the electromagnetic radiation detected by the probes and for converting the electromagnetic radiation signals to electrical signals; and

a processor coupled to the detector for receiving the electrical signals and for determining, based on the electrical signals an indication of a physical property of the biological sample.

20. The system of claim 19, wherein at least one of the plurality of frame members is translatable with respect to another frame member such that the volume of the interior region can be altered in at least one direction.

21. The system of claim 20, wherein the at least one translatable frame member can be translated to vary the volume of the interior region so that the biological sample can be placed proximal to the plurality of probes.

22. The system of claim 19, wherein at least two of the plurality of frame members are translatable in order to alter the volume of the interior region in at least two directions.

23. The system of claim 19, wherein the probe receiving locations are adapted to receive fiber optic probes and wherein the electromagnetic radiation probes comprise fiber optic probes.

24. The system of claim 23, wherein the probe receiving locations comprise a plurality of apertures for receiving the fiber optic probes.

25. The system of claim 24, comprising means for controlling advancement of each fiber optic probe in each aperture to position the fiber optic probe adjacent to the biological sample.

26. The system of claim 25, wherein the means for controlling advancement of each fiber optic probe in each aperture comprises a barrier located in a position proximal to the interior region to prevent the fiber optic probes from entering the interior region.

27. The system of claim 25, wherein the means for controlling advancement comprises an adapter couplable to one of the fiber optic probes and one of the apertures to limit advancement of the one probe in the one aperture.

28. The system of claim 27, wherein the plurality of fiber optic probes are fixedly attached to each other such that the adapter that limits advancement of the one fiber optic probe limits advancement of the remaining bundled fiber optic probe in their respective apertures.

29. The system of claim 23, wherein the fiber optic probes have a sensing depth of between about 1 and 2 mm.

30. The system of claim 23, wherein the fiber optic probes have a geometry comprising a central core comprising a plurality of illumination fibers surrounded by at least one concentric ring comprising a plurality of collection fibers.

31. The system of claim 19, wherein the frame members form a parallelepiped structure.

32. The system of claim 31, wherein the parallelepiped structure is a rectangular parallelepiped.

33. The system of claim 19, wherein the frame members are translucent or transparent.

34. The system of claim 19, wherein the probe receiving locations are spaced from each other so as to avoid cross-talk between adjacent probes.

35. The system of claim 34, wherein each of the apertures has a diameter of about 3.7 mm and adjacent apertures have a 2 mm radial separation.

36. The system of claim 19, wherein the biological sample comprises a turbid medium having a concentration of one or more fluorophores and wherein the processor is adapted to determine an indication of the concentration of the one or more fluorophores based on the detected electromagnetic radiation.

37. The system of claim 36, wherein the turbid medium is a biological tissue sample.

38. The system of claim 37, wherein the indication of the physical property of the biological tissue sample is indicative of the biological tissue sample comprising normal cells, pre-neoplastic cells, neoplastic cells, or combinations thereof.

39. The system of claim 36, wherein the turbid medium comprises one or more absorbers and one or more scatterers and wherein the processor is adapted to determine an indication of the concentration of the absorber and the scattering coefficient.

40. The system of claim 19, wherein the electromagnetic radiation probes are adapted to illuminate plural locations of the biological sample in parallel via different probe receiving locations.