Readable probe array for in vivo use

• US 8,140,148 B2
• Filed: 01/09/2007
• Issued: 03/20/2012
• Est. Priority Date: 01/20/1998
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Crowley, Robert J.
• Primary Examiner(s): Casler, Brian
• Assistant Examiner(s): COOK, CHRISTOPHER L
• Application Number:
  US11/621,415
• Publication Number:
  US 20070167719A1
• Time in Patent Office: 1,897 Days
• Field of Search: 600/317, 600/407, 600/476, 600/478
• US Class Current: 600/478
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/0097 by applying acoustic waves and detecting light, i.e. acoustooptic measurements
• 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
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

A disposable high-density, optically readable polydeoxynucleotide array with integral fluorescence excitation and fluorescence emission channels is described. The compact array size allows integration into several types of interventional devices such as catheters, guidewires, needles, and trocars and may be used intraoperatively. Highly sensitive monitoring of the metabolic and disease pathways of cells in vivo under varying chemical, genetic, and environmental conditions is afforded.

Claims

1. A body-insertable apparatus comprising:

an excitation source capable of generating radiation;

at least one probe disposed in a path of said radiation, said probe having an affinity to an analyte and situated in the apparatus to contact the analyte and receive the generated radiation at a same time;

a detector for detecting the optical properties of said probe, said detector also for converting optical signals representative of the detected optical properties to electrical signals; and

a housing adapted for reaching an area of interest within a body,

wherein said excitation source, said probe, and said detector are disposed in said housing.

2. The apparatus of claim 1 wherein said probe binds to at least one of an oligonucleotide and a protein.

3. The apparatus of claim 1 wherein said probe is fluorescently labeled.

4. The apparatus of claim 1 wherein said probe is attached to a substrate.

5. The apparatus of claim 1 wherein said probe comprises an array of sub-probes.

6. The apparatus of claim 5 wherein said array comprises a readable polydeoxynucleotide array.

7. The apparatus of claim 6 wherein said array is positioned adjacent to said detector.

8. The apparatus of claim 7 wherein said detector comprises a spectrometer module.

9. The apparatus of claim 8 wherein said spectrometer module is encapsulated in an at least partly transparent housing.

10. The apparatus of claim 5 wherein said array is disposed in a plurality of chambers within a frame.

11. The apparatus of claim 10 wherein said frame comprises at least one of a molded material and a foraminous material.

12. The apparatus of claim 1, further comprising optics that affect said path of radiation.

13. The apparatus of claim 12 wherein said optics comprise a mirror.

14. The apparatus of claim 13 wherein said mirror is adjustable.

15. The apparatus of claim 1 wherein said body-insertable apparatus is electrically connected to a processing unit.

16. The apparatus of claim 1 wherein said body-insertable apparatus is electrically connected to an amplifier.

17. The apparatus of claim 1 wherein said body-insertable apparatus is electrically connected to a display.

18. The apparatus of claim 1 wherein said excitation source comprises a light-emitting diode light source.

19. The apparatus of claim 1 wherein said excitation source provides excitation energy wavelengths in a range from about 1100 nm to about 250 nm.

20. The apparatus of claim 1 wherein said detector comprises a photodiode responsive to light emitted by said probe.

21. The apparatus of claim 1 wherein said detector comprises a light wavelength detection system.

22. The apparatus of claim 21 wherein said light wavelength detection system comprises a bandpass filter.

23. The apparatus of claim 1, further comprising a catheter, wherein said housing is disposed within the catheter.

24. The apparatus of claim 23 wherein said catheter defines one or more lumens extending through the length of the catheter.

25. The apparatus of claim 24 comprising means for delivering a drug, a reagent or a device.

26. The apparatus of claim 24 comprising means for providing suction sufficient to draw an analyte into proximity with said excitation source, said probe and said detector such that said analyte can be analyzed.

27. The apparatus of claim 24 comprising means for infusing fluids, reagents, drugs, wires or appliances.

28. The apparatus of claim 1 wherein said detector comprises multiple channels to detect light emission at multiple wavelengths.

29. The apparatus of claim 1, wherein said probe has readable optical properties when said analyte is in contact with said probe.

30. The apparatus of claim 1, wherein said probe includes a material sensitive to a gene or gene segment.

31. The apparatus of claim 1, wherein said probe is capable of linking to the analyte.

32. A method of performing in vivo examination of a mammalian body, said method comprising:

(a) providing a device comprising an excitation source, at least one probe having an affinity to an analyte, a detector, and a housing wherein said excitation source, said probe and said detector are disposed in said housing;

(b) inserting said device into said mammalian body until said probe contacts an analyte in an area of interest;

(c) generating radiation from said excitation source such that said probe is in a path of said radiation;

(d) detecting an optical signal representative of an optical property of said probe through said detector, when said analyte is in contact with said probe; and

(e) converting said optical signal to an electrical signal.

33. The method of claim 32, further comprising contacting said probe with an analyte comprising at least one of an oligonucleotide and a protein.

34. The method of claim 32, further comprising contacting said analyte with a fluorescently labeled probe.

35. The method of claim 32, further comprising attaching said probe to a substrate.

36. The method of claim 35, further comprising mixing said probe with an ink to form a probe-filled ink and depositing said probe-filled ink upon said substrate.

37. The method of claim 36, further comprising depositing a plurality of probe-filled inks upon said substrate in a specific ink pattern.

38. The method of claim 37, further comprising protecting said ink pattern with a topcoat.

39. The method of claim 38, further comprising providing said topcoat made of a dissolvable gel.

40. The method of claim 38, further comprising providing said topcoat made of a polymer material dissolvable only upon application of a solvent.

41. The method of claim 32, further comprising providing said probe with an array of sub-probes.

42. The method of claim 41, further comprising providing said array with a readable polydeoxynucleotide array.

43. The method of claim 41, further comprising providing said array in a plurality of chambers within a frame.

44. The method of claim 43, further comprising providing said frame made of at least one of a molded material and a foraminous material.

45. The method of claim 32, further comprising using optics to affect said path of radiation.

46. The method of claim 45 wherein said step of using optics comprises adjusting a mirror.

47. The method of claim 32, further comprising transmitting and processing said electrical signal.

48. The method of claim 32, further comprising amplifying said electrical signal.

49. The method of claim 32, further comprising displaying said electrical signal.

50. The method of claim 32, further comprising providing a detector comprising a spectrometer module.

51. The method of claim 50, further comprising encapsulating said spectrometer module in an at least partly transparent housing.

52. The method of claim 32, further comprising providing an excitation source that comprises a light-emitting diode.

53. The method of claim 32 wherein step (c) comprises generating radiation of wavelengths in a range from about 1100 nm to about 250 nm.

54. The method of claim 32, further comprising providing said detector comprising a photodiode responsive to said optical signal from said probe.

55. The method of claim 32, further comprising providing said detector comprising a light wavelength detection system.

56. The method of claim 55, further comprising providing said light wavelength detection system comprising a bandpass filter.

57. The method of claim 32, further comprising providing a catheter comprising said device.

58. The method of claim 32, further comprising providing a catheter having at least one lumen extending through the length of said catheter.

59. The method of claim 58, further comprising delivering a drug, a reagent, or a device through said lumen to or beyond a distal tip of said device to affect said area of interest.

60. The method of claim 58, further comprising using said lumen to provide suction such that said analyte is drawn into contact with said probe.

61. The method of claim 32, further comprising implanting said device in said mammalian body.

62. The method of claim 32, further comprising using a carrying device to deliver said device to the area of interest.

63. The method of claim 62, further comprising providing said carrying device selected from the group consisting of a hollow needle, a guidewire, a balloon catheter, an ultrasound catheter, an introducer sheath, and a balloon angioplasty catheter.

64. The method of claim 32, wherein said probe includes a material sensitive to a gene or gene segment.

65. The method of claim 32, further comprising linking said probe to the analyte.