Optical coherence tomographic detection of cells and compositions

• US 7,983,737 B2
• Filed: 05/26/2006
• Issued: 07/19/2011
• Est. Priority Date: 05/27/2005
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Cilingiroglu, Mehmet, Milner, Thomas E., Feldman, Marc D., Oh, Jung-Hwan
• Primary Examiner(s): Le; Long V
• Assistant Examiner(s): Rozanski; Michael T
• Application Number:
  US11/441,824
• Publication Number:
  US 20070038121A1
• Time in Patent Office: 1,880 Days
• Field of Search: 600/407, 600/473, 600/476
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: A61B 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61B 5/0515 Magnetic particle imaging
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61B 8/06 Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/13 Tomography A61B8/10, A61B8/12 take precedence; tomography for radiation diagnosis A61B6/02
• CPC Class Codes: G01N 21/1717 with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B

Abstract

Provided herein are systems and methods for the detection of cells and/or compositions using optical coherence tomography. The systems and methods comprise a plurality of magnets for applying a plurality of distinct magnetic field strengths to the cells and/or compositions and a phase sensitive optical coherence tomographic imaging modality for detecting the cells and/or compositions while same are disposed in the presence of at least one of the plurality of distinct magnetic field strengths.

Claims

1. A method for detecting a cell, comprising:

applying a first magnetic field strength to the cell, wherein the cell comprises a cellular membrane and a magnetically susceptible material;

applying a second magnetic field strength to the cell, wherein the second magnetic field strength is different from the first magnetic field strength and interacts with the magnetically susceptible material to cause a change in the cell relative to interaction of the cell with the first magnetic field strength; and

detecting the cell by detecting the change in the cell, wherein the change is detected using a phase sensitive frequency domain optical coherence tomographic imaging modality including a common path interferometer during the application of at least one of the first and second magnetic field strengths.

2. The method of claim 1, wherein the change is selected from the group consisting of:

movement of the cell, movement of the magnetically susceptible material, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

3. The method of claim 1, wherein the phase sensitive optical coherence tomographic imaging modality comprises using a probe for transmitting and receiving light energy to and from the cell.

4. The method of claim 3, wherein the probe further comprises a magnetic source for applying at least one of the first and second magnetic field strengths to the cell.

5. The method of claim 1, wherein at least one of the first and second magnetic field strengths is applied to the cell from a magnetic source located external to the probe.

6. The method of claim 1, wherein the magnetically susceptible material is located within the cell.

7. The method of claim 1, wherein the magnetically susceptible material is targeted to a location on the cellular membrane of the cell.

8. The method of claim 1, wherein the magnetically susceptible material has a non-zero magnetic susceptibility.

9. The method of claim 8, wherein the magnetically susceptible material comprises a material selected from the group consisting of iron oxide, iron, cobalt, nickel, and chromium.

10. The method of claim 1, wherein the magnetically susceptible material comprises a plurality of metallic nanoparticles.

11. The method of claim 10, wherein the nanoparticles are substantially spherical and have a diameter from about 0.1 nanometers (nm) to about 1000.0 nm.

12. The method of claim 10, wherein the nanoparticles are asymmetrical in shape.

13. The method of claim 12, wherein the largest cross sectional dimension of the nanoparticles is from about 0.1 nanometers (nm) to about 1000.0 nm in length.

14. The method of claim 9, wherein the cell is detected in vivo and the magnetically susceptible material is administered to the subject.

15. The method of claim 14, wherein the cell is a macrophage and wherein at least one nanoparticle is located within the macrophage.

16. The method of claim 15, wherein the macrophage is located in an atherosclerotic plaque within the subject.

17. The method of claim 15, wherein the macrophage is located within the eye of the subject.

18. The method of claim 14, wherein at least one of the nanoparticles is configured to localize to a target site within the subject.

19. The method of claim 18, wherein the target site is a neoplastic cell.

20. The method of claim 18, wherein the target site is an extracellular domain of a protein.

21. The method of claim 18, wherein in the cell comprises the target site, and wherein the cell is located in the subject at an anatomical location selected from the group consisting of a lung, bronchus, intestine, stomach, colon, eye, heart, blood vessel, cervix, bladder, urethra, skin, muscle, liver, kidney, and blood.

22. The method of claim 18, wherein the cell comprises the target site and wherein the cell is selected from the group consisting of a neoplastic cell, a squameous cell, a transitional cell, a basal cell, a muscle cell, an epithelial cell, and a mucosal cell.

23. The method of claim 18, wherein the nanoparticle comprises an antibody or fragment thereof.

24. The method of claim 23, wherein the antibody or fragment thereof is conjugated to the surface of the nanoparticle.

25. The method of claim 18, wherein the nanoparticle comprises a peptide or a fragment thereof.

26. The method of claim 25, wherein the peptide or fragment thereof is conjugated to the surface of the nanoparticle.

27. The method of claim 1, further comprising the steps of capturing one or more lines of phase sensitive light energy data using the phase sensitive optical coherence tomography modality, and generating a phase sensitive optical coherence tomographic image from the one or more lines of phase sensitive light energy data captured using the phase sensitive optical coherence tomography modality, wherein at least one line of the one or more lines of phase sensitive light energy data is captured during the application of at least one of the first and second magnetic field strengths.

28. The method of claim 27, wherein the step of capturing one or more lines of phase sensitive light energy data comprises:

generating light energy;

transmitting at least a first portion of the generated light energy onto a reference reflector wherein at least a portion of the transmitted first portion of light energy is reflected by the reference reflector;

transmitting at least a second portion of the generated light energy to contact the cell wherein at least a portion of the light energy that contacts the cell is reflected by the cell;

receiving the light energy reflected by the reference reflector and by the cell;

combining the received light energy from the cell and reference reflector, wherein the received light energy interferes; and

processing the combined light energy to produce the phase sensitive optical coherence data line.

29. The method of claim 28, wherein movement of the cell is detected.

30. The method of claim 28, wherein a change in the cellular membrane'"'"'s tension level or internal strain field is detected.

31. The method of claim 28, wherein the image produced has a phase sensitive resolution of at least about 30.0 nanometers (nm), 25.0 nm, 15.0 nm, 10.0 nm, 5.0 nm, 4.0 nm, 3.0 nm, or 2.0 nm.

32. The method of claim 27, wherein the step of capturing one or more lines of phase sensitive light energy data comprises:

generating light energy;

transmitting at least a first portion of the generated light energy onto a reference reflector wherein at least a portion of the transmitted first portion of light energy is reflected by the reference reflector;

transmitting at least a second portion of the generated light energy to contact the magnetically susceptible material wherein at least a portion of the light energy that contacts the magnetically susceptible material is reflected by the magnetically susceptible material;

receiving the light energy reflected by the reference reflector and by the magnetically susceptible material;

combining the received light energy, wherein the received light energy interferes; and

processing the combined light energy to produce the phase sensitive optical coherence data line.

33. The method of claim 32, wherein movement of the magnetically susceptible material is detected.

34. The method of claim 32, wherein the image produced has a phase sensitive resolution of at least about 30.0 nanometers (nm), 25.0 nm, 15.0 nm, 10.0 nm, 5.0 nm, 4.0 nm, 3.0 nm, or 2.0 nm.

35. The method of claim 27, wherein a plurality of phase sensitive light energy data lines are captured and used to construct the image.

36. The method of claim 35, wherein the plurality of phase sensitive light energy data lines are spatially and temporally distinct and wherein the image comprises a B-mode image frame comprising at least two of the lines.

37. The method of claim 35, wherein the plurality of phase sensitive light energy data lines are temporally distinct and wherein the image comprises a M-mode image comprising at least two of the lines.

38. The method of claim 35, wherein at least a first phase sensitive light energy data line is captured during the application of the first magnetic field strength, wherein at least a second phase sensitive light energy data line is captured during application of the second magnetic field strength, and wherein the captured lines are used to create the image.

39. The method of claim 35, wherein the first magnetic field strength has a first predetermined magnetic flux density and the second magnetic field strength has a second predetermined magnetic flux density.

40. The method of claim 39, wherein the first predetermined magnetic flux density is less than the second predetermined magnetic flux density.

41. A method for detecting a cell, comprising:

applying a first time-varying magnetic field strength to a cell, wherein the cell comprises a cellular membrane and a magnetically susceptible material and wherein the first magnetic field strength interacts with the magnetically susceptible material to induce an electrical eddy current within the magnetically susceptible material;

applying a second magnetic field strength to the cell that interacts with the induced eddy current to cause a change in the cell; and

detecting the cell by detecting the change in the cell caused by the interaction of the second magnetic field strength with the induced eddy current, wherein the change is detected using a phase sensitive frequency domain optical coherence tomographic imaging modality including a common path interferometer.

42. The method of claim 41, wherein the change in the cell is selected from the group consisting of:

movement of the cell, movement of the magnetically susceptible material, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

43. The method of claim 41, wherein the magnetically susceptible material is non-magnetic.

44. The method of claim 43, wherein the magnetically susceptible material comprises gold, silver, or zinc.

45. The method of claim 41, wherein the magnetically susceptible material is magnetic.

46. The method of claim 41, wherein the phase sensitive optical coherence tomographic imaging modality comprises using a probe for transmitting and receiving light energy to and from the cell.

47. The method of claim 46, wherein the probe further comprises a magnetic source for applying at least one of the first and second magnetic field strengths to the cell.

48. The method of claim 41, wherein at least one of the first and second magnetic field strengths is applied to the cell from a magnetic source located external to the probe.

49. The method of claim 41, wherein the magnetically susceptible material is located within the cell.

50. The method of claim 41, wherein the magnetically susceptible material is targeted to location on the cellular membrane of the cell.

51. The method of claim 41, wherein the magnetically susceptible material comprises a plurality of metallic nanoparticles.

52. The method of claim 51, wherein the cell is detected in vivo.

53. A system for detecting a cell, comprising:

a plurality of magnets configured to apply first and second distinct magnetic field strengths to the cell, wherein the cell comprises a cellular membrane and a magnetically susceptible material, and wherein the second magnetic field strength interacts with the magnetically susceptible material to cause a change in the cell relative to interaction of the cell with the first magnetic field strength; and

a phase sensitive frequency domain optical coherence tomographic imaging modality including a common path interferometer for detecting the change in the cell while it is in the presence of at least one the first and second distinct magnetic field strengths.

54. The system of claim 53, wherein the phase sensitive optical coherence tomographic imaging modality comprises using a probe for transmitting and receiving light energy to and from the cell.

55. The system of claim 54, wherein the probe further comprises at least one of the plurality of magnets.

56. The system of claim 55, wherein at least one of the plurality of magnets is located external to the probe.

57. The system of claim 53, wherein the phase sensitive optical coherence tomographic imaging modality comprises using:

a light source, a light splitter, a probe and a reference reflector, wherein light energy generated by the light source can be transmitted to and split by the splitter for transmission to the reference reflector and to the probe, wherein the probe is configured to transmit at least a portion of the light energy transmitted thereto into a target cell and to receive reflected light energy from the target cell, and wherein the reference reflector is configured to reflect at least a portion of the light energy transmitted thereto; and

a processor for processing reflected light energy from the reference reflector and light energy received by the probe to produce a phase sensitive optical coherence tomography image.

58. The method of claim 57, wherein the probe further comprises a single optical fiber and a rotary reflector in optical communication with the single optical fiber.

59. The system of claim 57, wherein the probe comprises the reference reflector.

60. A method for detecting a composition comprising metal, the method comprising:

applying a first magnetic field strength to the composition;

applying a second magnetic field strength to the composition, wherein the second magnetic field strength is different from the first magnetic field strength and the second magnetic field strength interacts with the composition to cause a change in the composition relative to interaction of the composition with the first magnetic field strength; and

detecting the composition using a phase sensitive frequency domain optical coherence tomographic imaging modality including a common path interferometer during the application of at least one of the first and second magnetic field strengths.

61. The method of claim 60, wherein the composition is located inside of a cell and the change in the composition causes a change in the cell.

62. The method of claim 61, wherein the step of detecting the composition further includes detecting the change in the cell.

63. The method of claim 62, wherein the change in the cell that is detected is selected from the group consisting of:

movement of the cell, movement of the metallic composition, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

64. The method of claim 61, wherein the composition is connected to non-cellular biological matter.

65. The method of claim 64, wherein the non-cellular biological matter is selected from the group consisting of:

a protein, a lipid, a peptide, and a nucleic acid.

66. The method of claim 60, wherein the composition is connected to the external surface of the cellular membrane of a cell and the change in the composition causes a change in the cell.

67. The method of claim 66, wherein the step of detecting the composition further includes detecting the change in the cell.

68. The method of claim 67, wherein the change in the cell that is detected is selected from the group consisting of:

movement of the cell, movement of the metallic composition, a change in the cellular membrane tension level, and a change in the internal strain field of the cell.

69. The method of claim 60, wherein the composition comprises a paramagnetic or magnetic material.

70. A method for detecting a magnetically susceptible material, the method comprising:

applying a first magnetic field strength to the magnetically susceptible material;

applying a second magnetic field strength to the magnetically susceptible material, wherein the second magnetic field strength is different from the first magnetic field strength and the second magnetic field strength interacts with the magnetically susceptible material to cause a change in the magnetically susceptible material relative to interaction of the magnetically susceptible material with the first magnetic field strength; and

detecting the magnetically susceptible material using a phase sensitive frequency domain optical coherence tomographic imaging modality including a common path interferometer during the application of at least one of the first and second magnetic field strengths.

71. The method of claim 70, wherein the magnetically susceptible material comprises a magnetic or paramagnetic material.