System, method and apparatus for the detection of patient-borne fluorescing nanocrystals

• US 7,689,269 B2
• Filed: 05/10/2007
• Issued: 03/30/2010
• Est. Priority Date: 05/10/2007
• Status: Active Grant

• Current Assignee: Actis Limited
• Original Assignee: Actis Limited
• Inventors: Olson, Karl W., Thurston, Marlin O.
• Primary Examiner(s): Winakur; Eric F
• Assistant Examiner(s): Rozanski; Michael T
• Application Number:
  US11/801,549
• Publication Number:
  US 20080281172A1
• Time in Patent Office: 1,055 Days
• Field of Search: 600/436, 600/476, 600/477, 600/431, 250/336.1, 424/9.6, 422/82.07, 422/82.08, 422/82.11, 435/7.1, 435/7.25, 436/172
• US Class Current: 600/477
• 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 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/027 Control of working procedures of a spectrometer; Failure detection; Bandwidth calculation
• CPC Class Codes: G01J 3/28 Investigating the spectrum using colour filters G01J3/51
• CPC Class Codes: G01J 3/2889 Rapid scan spectrometers; Time resolved spectrometry
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53

Abstract

System, method and apparatus wherein a probe employing non-imagining optics is utilized in conjunction with a fluorescing nanocrystal tracer at the body of a patient. Excitation components within the probe working end are utilized to excite the nanocrystals to fluoresce at wavelengths in the near infrared region, such fluorescent energy is homogenized by interacting with involved tissue to provide a uniform fluorescing intensity over the surface of a photo-detector. Initialization and background determination procedures are described along with a technique for determining statistically significant levels of fluorescing activity.

Claims

1. A system for detecting fluorescing nanocrystal tracers at the body of a patient, such nanocrystals being responsive to wavelength defined excitation energy to fluoresce at one or more detection wavelengths, comprising:

a probe having a working portion with a forward transmission surface, a photo-detector having a detector output corresponding with non-imaged impinging fluorescent radiation when enabled, mounted in adjacency with said surface, a longpass filter operatively associated with the photo-detector and one or more excitation components energizable to provide said excitation energy forwardly of said transmission surface, and a support for supporting said working portion; and

a control assembly, responsive in an initialization mode to derive and store a reference value not operationally associated with said tracer, responsive in a range mode to energize said excitation components under predetermined modulation and enable the photo-detector while the transmission surface is adjacent tissue representing background to derive and store a mean squelch intensity level corresponding with said detection wavelengths and, when in a scan mode wherein said transmission surface is moved in adjacency with tissue suspected of being neoplastic, to energize the excitation components under predetermined modulation and enable the photo-detector to derive the detector output corresponding with said detection wavelengths with intensity levels minus said reference value as a corrected detector output, and responsive to provide a humanly perceptible cue when said corrected detector output represents an intensity level statistically significantly above said mean squelch intensity level.

2. The system of claim 1 in which:

said control assembly predetermined modulation is clock pulse-based.

3. The system of claim 1 in which:

said tracer incorporates a fluorescing nanocrystal and specifically binds a marker produced by or associated with neoplastic tissue;

said detection wavelengths are in the near-infrared region; and

said excitation components comprise one or more light emitting diodes located adjacent said transmission surface in spaced adjacency with said photo-detector.

4. The system of claim 3 in which:

said light emitting diodes are canted inwardly to an extent effecting a general convergence of their light outputs at a distance therefrom corresponding with the tissue penetration capability of said wavelength defined excitation energy.

5. The system of claim 1 in which:

said corrected detector output, when representing a statistically significant intensity level, exhibits an intensity level about three standard deviations above said mean squelch intensity level.

6. The system of claim 1 in which:

said probe support is configured generally as a cylinder having a length effective for hand grasping.

7. The system of claim 1 in which:

said probe support is configured to be slideably retained upon a human finger.

8. The system of claim 1 in which:

said probe is configured as a laparoscopic instrument in which said probe support is generally an elongate cylindrical shaft extending along a shaft axis.

9. The system of claim 8 in which:

said working portion forward transmission surface is within a plane generally parallel to said shaft axis.

10. The system of claim 1 in which:

said tracer incorporates a first type fluorescing nanocrystal exhibiting a rapid fluorescing reaction response occurring substantially only during its excitation and specifically binds a marker-produced by or associated with neoplastic tissue; and

said control assembly predetermined modulation is clock pulse-based, is responsive to an excitation clock pulse to energize said excitation components for an excitation interval and to simultaneously enable the photo-detector.

11. The system of claim 10 in which:

said control assembly is responsive to a clock pulse occurring subsequent to said excitation clock pulse to enable the photo-detector in the absence of excitation energy and determine an ambient related value of detector output corresponding with any ambient illumination; and

said corrected detector output is further derived with subtraction of said ambient related value.

12. The system of claim 1 in which:

said tracer comprises a first type fluorescing nanocrystal;

said tracer incorporates a second type fluorescing nanocrystal exhibiting decaying fluorescence at said detection wavelength for a follow-on interval subsequent to the termination of energization of the excitation components, and specifically binds a marker; and

said control assembly predetermined modulation is clock pulse-based, is responsive to an excitation clock pulse to energize said excitation components and enables the photo-detector for a sampling interval subsequent to the termination of energization of the excitation component.

13. The system of claim 12 in which:

said control assembly is responsive to the intensities of said decaying fluorescence to compute total fluorescing intensity occurring during both the energization of the excitation components and during the sampling interval.

14. The system of claim 13 in which:

the computation of total fluorescing intensity is by convolution.

15. The system of claim 12 in which:

said control assembly is responsive to a clock pulse occurring subsequent to said sampling interval to enable the photo-detector in the absence of excitation energy and determine an ambient related value of detector output corresponding with any ambient illumination; and

said corrected detector output is further derived with subtraction of said ambient-related value.

16. The system of claim 1 further comprising:

an initialization chamber removably receptive of said probe forward transmission surface in light-tight relationship and having a polymeric material located forwardly of said surface exhibiting scattering characteristics similar to those of tissue;

said control assembly initialization mode is carried out with said transmission surface being located within said chamber in light-tight relationship, and enabling said photo-detector to determine and store any electronic noise and dark current value;

said initialization mode being further carried out with said transmission surface being located within said chamber in light-tight relationship and energizing said excitation components and enabling said photo-detector to determine and store an intensity value of scattered excitation light; and

said control assembly is responsive to combine said electronic noise and dark current value with said intensity value of scattered excitation light to provide said reference value.

17. The system of claim 16 wherein:

said tracer incorporates a first type fluorescing nanocrystal, exhibiting a substantially immediate reaction response to excitation energy, and specifically binds a marker produced by or associated with neoplastic tissue; and

said control assembly, when in said initialization mode, effects energization of said excitation components for an excitation interval while simultaneously enabling the photo-detector to derive said intensity value of scattered excitation light.

18. The system of claim 16 wherein:

said tracer incorporates a second type fluorescing nanocrystal exhibiting decaying fluorescence at said detection wavelength for a follow-on interval occurring subsequent to the termination of energization of the excitation components, and specifically binds a marker produced by or associated with neoplastic tissue; and

said control assembly, when in said initialization mode, effects energization of said excitation components for an excitation interval, then enables the photo-detector for a sampling interval to derive said intensity value of scattered excitation light.

19. The system of claim 1 further comprising:

a squelch switch located at said probe support and/or the control assembly, hand actuateable to derive and store said mean squelch intensity level.

20. The system of claim 1 further comprising:

a record switch located at said probe support and/or the control assembly, hand actuateable for a short interval to effect recordation of the corrected data output in a data file of said control assembly.

21. The system of claim 20 in which:

said record switch, when actuated for said short interval effects at said control assembly, a voice annunciation of said corrected data output.

22. The system of claim 21 in which:

said record switch when actuated for a recording interval greater than said short interval effects a voice recordation at said control assembly.