Optical tomography of small objects using parallel ray illumination and post-specimen optical magnification

• US 6,944,322 B2
• Filed: 12/03/2002
• Issued: 09/13/2005
• Est. Priority Date: 03/28/2001
• Status: Expired due to Term

• Current Assignee: VisionGate, Inc.
• Original Assignee: VisionGate, Inc.
• Inventors: Johnson, Roger H., Nelson, Alan C.
• Primary Examiner(s): Johns, Andrew W.
• Assistant Examiner(s): NAKHJAVAN, SHERVIN K
• Application Number:
  US10/308,309
• Publication Number:
  US 20040001618A1
• Time in Patent Office: 1,015 Days
• Field of Search: 382/120, 382/129, 382/131, 382/133, 435/448, 600/309, 600/310, 378/6, 378/7, 378/8, 378/44, 378/45, 378/49, 378/50, 430/8, 430/21, 430/139, 430/503, 430/508, 430/511, 702/19, 702/21, 702/28
• US Class Current: 382/128
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/147 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2021/0307 Insert part in cell
• CPC Class Codes: G01N 2021/0392 Nonplanar windows
• CPC Class Codes: G01N 2021/052 Tubular type; cavity type; multireflective
• CPC Class Codes: G01N 2021/1772 Array detector
• CPC Class Codes: G01N 2021/1787 Tomographic, i.e. computerised reconstruction from projective measurements
• CPC Class Codes: G01N 2021/5919 Determining total density of a zone
• CPC Class Codes: G01N 2021/5923 Determining zones of density; quantitating spots
• CPC Class Codes: G01N 2021/5957 using an image detector type detector, e.g. CCD
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• 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 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 2201/0696 Pulsed
• CPC Class Codes: G01N 2223/419 computed tomograph
• CPC Class Codes: G01N 23/046 using tomography, e.g. computed tomography [CT]
• CPC Class Codes: G06T 11/006 Inverse problem, transformation from projection-space into object-space, e.g. transform methods, back-projection, algebraic methods

Abstract

A parallel-beam optical tomography system for imaging an object of interest includes a parallel ray beam radiation source that illuminates the object of interest with a plurality of parallel radiation beams. After passing through the object of interest the pattern of transmitted or emitted radiation intensities is magnified by a post specimen optical element or elements. An object containing tube is located within an outer tube, wherein the object of interest is held within or flows through the object containing tube. A motor may be coupled to rotate and/or translate the object containing tube to present differing views of the object of interest. One or more detector arrays are located to receive the emerging radiation from the post specimen magnifying optic. Two- or three-dimensional images may be reconstructed from the magnified parallel projection data.

Claims

1. A parallel-beam optical tomography system for imaging an object of interest comprising:

a plurality of parallel beam radiation sources for illuminating the object of interest with a plurality of parallel radiation beams; and

an object containing tube, wherein the object of interest is held within the object containing tube, and wherein the object containing tube has a reconstruction cylinder positioned around the object containing tube, wherein the reconstruction cylinder holds the plurality of parallel beam radiation sources in a geometrical arrangement around a circumference of a sample including the object of interest, and wherein the reconstruction cylinder further includes a detector array located to receive emerging radiation from the illuminated object of interest.

2. The parallel-beam optical tomography system of claim 1 wherein the object of interest comprises a cell.

3. The parallel-beam optical tomography system of claim 1 wherein at least one of the plurality of parallel beam radiation sources comprises a laser.

4. The parallel-beam optical tomography system of claim 3 wherein the laser emits radiation in the visible portion of the electromagnetic spectrum.

5. The parallel-beam optical tomography system of claim 3 wherein the laser emits radiation in the ultraviolet portion of the electromagnetic spectrum.

6. The parallel-beam optical tomography system of claim 1 wherein the object of interest includes a molecular probe.

7. The parallel-beam optical tomography system of claim 1 wherein the detector array comprises a detector array selected from the group consisting of solid state sensors, charge coupled device sensors, complementary metal oxide semiconductor sensors and time delay and integration sensors.

8. The parallel-beam optical tomography system of claim 1 wherein the object containing tube is coupled to a mechanical stage or micromanipulator that rotates the object containing tube to present differing views of the object of interest.

9. The parallel-beam optical tomography system of claim 1 wherein the object containing tube is within an outer tube having an optically flat input surface and a concave output surface or plano-concave lens, where the concave outer surface or plano-concave lens diverges radiation emerging from the outer tube after passing through the object of interest.

10. The parallel-beam optical tomography system of claim 9 wherein the outer tube further comprises a space around the object containing tube in communication with a port for filling the space around the object containing tube with optical oil having the same index of refraction as the outer tube and the object containing tube.

11. The parallel-beam optical tomography system of claim 1 wherein the parallel ray beam radiation source is selected from the group consisting of a laser,

a laser-fiber bundle combination,

an aperture in front of a laser or other high intensity photon source,

an aperture utilizing surface plasmon focusing of photons on both the entry and exit sides of the pinhole,

an optical fiber with a small cross-section,

a virtual point source from a short focal length lens in front of a photon source, and

an electron beam that irradiates a point on a phosphor surface, and combinations of the aforesaid elements.

12. The parallel-beam optical tomography system of claim 1 wherein the object containing tube comprises a flow tube.

13. The parallel-beam optical tomography system of claim 12, wherein the object of interest has a flow velocity, and wherein the geometrical arrangement comprises an arrangement from the group consisting of a series of partial circumferences arranged along the z-axis wherein each partial circumference includes at least one source-detector pair, and a helix having a pitch that is a function of the flow velocity.

14. A parallel-beam optical tomography system for imaging an object of interest comprising:

a parallel beam radiation source for illuminating the object of interest with a plurality of parallel radiation beams;

an outer tube having an optically flat input surface and a convex output surface or convex lens, where the convex output surface or convex lens focuses radiation emerging from the outer tube after passing through the object of interest;

an object containing tube located within the outer tube, wherein the object of interest is held within the object containing tube;

a mechanical stage or micromanipulator coupled to rotate the object containing tube to present differing views of the object of interest;

a pinhole aperture located at the focal point of the convex lens and arranged to produce a cone beam of emergent radiation; and

a detector array located to receive the cone beam of emergent radiation from the pinhole aperture.

15. The parallel-beam optical tomography system of claim 14 wherein the object of interest comprises a cell.

16. The parallel-beam optical tomography system of claim 14 wherein the parallel beam radiation source comprises a laser.

17. The parallel-beam optical tomography system of claim 14 wherein the laser emits radiation in the visible portion of the electromagnetic spectrum.

18. The parallel-beam optical tomography system of claim 14 wherein the laser emits radiation in the ultraviolet portion of the electromagnetic spectrum.

19. The parallel-beam optical tomography system of claim 14 wherein the outer tube further comprises a port and space around the object containing tube filled with optical oil having the same index of refraction as the outer tube and object containing tube.

20. The parallel-beam optical tomography system of claim 14 wherein the object of interest includes a molecular probe.

21. The parallel-beam optical tomography system of claim 14 wherein the detector array comprises a detector array selected from the group consisting of solid state sensors, charge coupled device sensors, complementary metal oxide semiconductor sensors and time delay and integration sensors.

22. The parallel-beam optical tomography system of claim 14 further comprising a plano-concave lens, or other diverging or magnifying optic located between the pinhole aperture and the detector array.

23. The parallel-beam optical tomography system of claim 14 wherein the object containing tube comprises a flow tube and a reconstruction cylinder is positioned around the object containing tube, wherein the reconstruction cylinder incorporates the pinhole aperture and a plurality of additional pinhole apertures in a geometrical arrangement around a circumference of a sample including the object of interest for illuminating the object of interest and the reconstruction cylinder further includes the detector array and a plurality of additional detector arrays located to receive emissions from the illuminated object of interest.

24. A parallel-beam optical tomography system for imaging an object of interest comprising:

a plurality of parallel beam radiation sources for illuminating the object of interest, each of the plurality of parallel beam radiation sources generating a plurality of parallel radiation paths at a differing angle of view with respect to the object of interest;

an outer tube having a plurality of optically flat input surfaces and a plurality of corresponding concave output surfaces or concave lenses, where the plurality of corresponding concave output surfaces or concave lenses diverge radiation emerging from the outer tube after passing through the object of interest;

an object containing tube located within the outer tube, wherein the object of interest is held within the object containing tube; and

a plurality of detector arrays, where each of the plurality of detector arrays is located to receive the emerging radiation from one or more of the plurality of concave output surfaces.

25. The parallel-beam optical tomography system of claim 24 wherein the object containing tube incorporates a mechanism for movement of the object containing tube.

26. The parallel-beam optical tomography system of claim 24 wherein the object of interest comprises a cell.

27. The parallel-beam optical tomography system of claim 24 wherein the plurality of parallel beam radiation sources comprises a plurality of lasers.

28. The parallel-beam optical tomography system of claim 27 wherein the plurality of lasers emits radiation in the visible portion of the electromagnetic spectrum.

29. The parallel-beam optical tomography system of claim 27 wherein the plurality of lasers emits radiation in the ultraviolet portion of the electromagnetic spectrum.

30. The parallel-beam optical tomography system of claim 27 wherein the outer tube further comprises a port and space around the object containing tube is filled with optical oil having the same index of refraction as the outer tube and object containing tube.

31. The parallel-beam optical tomography system of claim 24 wherein the object of interest includes a molecular probe.

32. The parallel-beam optical tomography system of claim 24 wherein the plurality of detector arrays comprises a detector array selected from the group consisting of solid state sensors, charge coupled device sensors, complementary metal oxide semiconductor sensors and time delay and integration sensors.

33. The parallel-beam optical tomography system of claim 24 wherein the plurality of parallel beam radiation sources comprises a plurality of optical fibers or fiber bundles coupled to at least one laser.

34. The parallel-beam optical tomography system of claim 24 wherein the object containing tube comprises a flow tube and a reconstruction cylinder is positioned around the object containing tube, wherein the reconstruction cylinder holds the plurality of parallel beam radiation sources in a geometrical arrangement around a circumference of a sample including the object of interest for illuminating the object of interest and the reconstruction cylinder further holds the plurality of detector arrays.

35. The parallel-bear optical tomography system of claim 34 wherein the object of interest has a flow velocity, and wherein the geometrical arrangement comprises an arrangement from the group consisting of a series of partial circumferences arranged along the z-axis wherein each partial circumference includes at least one source-detector pair, and a helix having a pitch that is a function of the flow velocity.

36. A parallel-beam optical tomography system for imaging an object of interest comprising:

a plurality of parallel beam radiation sources for illuminating the object of interest, each of the plurality of parallel beam radiation sources generating a plurality of parallel radiation paths at a differing angle of view of the object of interest;

an outer tube having a plurality of optically flat input surfaces and a plurality of corresponding convex output surfaces or convex lenses, where the plurality of corresponding convex output surfaces or convex lenses focus radiation emerging from the outer tube after passing through the object of interest;

an object containing tube located within the outer tube, wherein the object of interest is held within the object containing tube;

a plurality of pinhole apertures, where each of the plurality of pinhole apertures receives radiation from one of the plurality of corresponding convex output surfaces or lenses so as to produce an emergent cone beam; and

a plurality of detector arrays, where each of the plurality of detector arrays is located to receive the emerging radiation from one of the plurality of pinhole apertures.

37. The parallel-beam optical tomography system of claim 36 that may incorporate a mechanism for movement of the tube.

38. The parallel-beam optical tomography system of claim 36 wherein the object of interest comprises a cell.

39. The parallel-beam optical tomography system of claim 36 wherein the plurality of parallel beam radiation sources comprises a plurality of lasers.

40. The parallel-beam optical tomography system of claim 39 wherein the plurality of lasers emits radiation in the visible portion of the electromagnetic spectrum.

41. The parallel-beam optical tomography system of claim 39 wherein the plurality of lasers emits radiation in the ultraviolet portion of the electromagnetic spectrum.

42. The parallel-beam optical tomography system of claim 36 wherein the plurality of parallel beam radiation sources comprises a plurality of optical fibers or fiber bundles coupled to at least one laser.

43. The parallel-beam optical tomography system of claim 36 wherein the outer tube further comprises a port and space around the object containing tube is filled with optical oil having the same index of refraction as the outer and object containing tubes.

44. The parallel-beam optical tomography system of claim 36 wherein the object of interest includes a probe.

45. The parallel-beam optical tomography system of claim 36 wherein the plurality of detector arrays comprise a detector array selected from the group consisting of solid state sensors, charge coupled device sensors, complementary metal oxide semiconductor sensors and time delay and integration sensors.

46. The parallel-beam optical tomography system of claim 36 further comprising a plurality of optical elements between the plurality of pinhole apertures and the plurality of detector sensor arrays.

47. The parallel-beam optical tomography system of claim 46 wherein the plurality of optical elements are selected from the group consisting of plano-concave lenses, magnifying optical elements and diverging optical elements.

48. The method of claim 46 wherein the reconstruction cylinder has more than one plane of point sources with the associated planes of sensors where each plane of sources and associated sensors are radially offset from the previous to capture different perspectives.

49. The parallel-beam optical tomography system of claim 36 wherein the object containing tube comprises a flow tube and a reconstruction cylinder is positioned around the object containing tube, wherein the reconstruction cylinder holds the plurality of pinhole apertures and the plurality of detector arrays.

50. The parallel-beam optical tomography system of claim 49, wherein the object of interest has a flow velocity, and wherein the geometrical arrangement comprises an arrangement from the group consisting of a series of partial circumferences arranged along the z-axis wherein each partial circumference includes at least one pinhole aperture-detector pair, and a helix having a pitch that is a function of the flow velocity.

51. A method for three dimensional reconstruction of an object of interest comprising the steps of:

packing at least one object of interest into a linear container;

moving the linear container at a rate of translation;

illuminating the at least one object of interest with at least one parallel beam radiation source; and

generating at least one projection image with a time delay and integration (TDI) image sensor having a line transfer rate synchronized to the rate of translation.

52. The method of claim 51 wherein the at least one object of interest is a cell or a cell nucleus.

53. A method for three dimensional reconstruction of an object of interest using a reconstruction cylinder design wherein a plane of point sources and a plane of sensors are parallel and concentric, one above the other, and wherein the reconstruction cylinder has an arrangement of sources and detectors around a circumference of a sample, the method comprising the steps of:

(a) injecting objects of interest into a flow stream of controlled velocity;

(b) illuminating the object of interest with a plurality of parallel optical projection beams; and

(c) generating a set of projection images at a plurality of angles for each object as it flows through the reconstruction cylinder.

54. A method for three dimensional reconstruction of an object of interest using a reconstruction cylinder including at least one plane of point sources and at least one plane of sensors that are parallel and concentric to the at least one plane of point sources, one above the other, and arranged around a circumference of a sample in a linear container including at least one object of interest, the method comprising the steps of:

(a) packing the at least one object of interest into a linear container;

(b) illuminating the at least one object of interest with a plurality of parallel optical projection beams;

(c) translating the linear container until a selected object of interest is located within a region of the plurality of optical projection beams;

(d) centering the selected object of interest as necessary;

(e) generating a set of projection images from the selected object of interest at a plurality of angles; and

(f) repeating the steps (b) through (e) until the selected object of interest has been scanned.

55. The method of claim 54 wherein the reconstruction cylinder has more than one plane of point sources with the associated planes of sensors where each plane of point sources and associated sensors are radially offset from each other to capture different perspectives.

56. The method of claim 54 wherein the step of generating a set of projection images at a plurality of angles further comprises the step of selecting individual transaxial images through the imaged object as reconstructed from a subset of the data acquired by the sensor arrays.