OPTICAL TOMOGRAPHY SYSTEM WITH HIGH-SPEED SCANNER

• US 20100214639A1
• Filed: 02/23/2009
• Published: 08/26/2010
• Est. Priority Date: 02/23/2009
• Status: Active Grant

• Current Assignee: VisionGate, Inc.
• Original Assignee: VisionGate, Inc.
• Inventors: Watson, Mathew D., Hayenga, Jon W.
• Granted Patent: US 8,254,023 B2
• Time in Patent Office: Days
• US Class Current: 359/213.100
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G02B 21/002 Scanning microscopes scanning near field optical microscopes G01Q60/18
• CPC Class Codes: G02B 21/025 with variable magnification variable magnification G02B15/00
• CPC Class Codes: G02B 27/0075 with means for altering, e.g. increasing, the depth of field or depth of focus

Abstract

An object of interest is illuminated within the field of view of a microscope objective lens located to receive light passing through the object of interest. Light transmitted through the microscope objective lens impinges upon a variable power element. The variable power element is driven with respect to the microscope objective lens to scan through multiple focal planes in the object of interest. Light transmitted from the variable power element is sensed by a sensing element or array.

Claims

1. An optical projection tomography system for imaging an object of interest, the optical projection tomography system comprising:

an illumination source;

a carrier for holding the object of interest, a portion of which is located within the region illuminated by the light source, wherein the object of interest has at least one feature of interest located within the carrier;

a microscope objective lens located to receive light passing through the carrier, the microscope objective lens located on an optical path;

a variable power element located along the optical path;

a second lens for receiving and transmitting light emitted from the variable power element; and

a light sensor located to receive light transmitted from the optical element.

2. The system of claim 1 wherein the variable power element comprises:

a beam splitter;

a scan lens;

a scan mirror having a reflective surface for receiving light transmitted through the scan lens, where the microscope objective assembly, the beam splitter the scan lens and the scan mirror are aligned along the optical path; and

a driver coupled to oscillate the scan mirror along the optical path such that the reflecting surface remains perpendicular to the optical path whereby the oscillating scan mirror scans through a plurality of focal planes in the carrier.

3. The system of claim 2 wherein the second lens includes a tube lens;

and wherein the beam splitter is also arranged to direct reflected light from the scan mirror through the tube lens.

4. The system of claim 2 wherein the scan lens has a numerical aperture (NA) value and an entrance pupil, and the microscope objective lens has an exit pupil, the system further comprising:

an optical relay positioned to image the microscope objective lens exit pupil onto the scan lens entrance pupil; and

where the microscope objective lens has an NA value that matches the scan lens NA value divided by the transverse magnification value (mT) between the object and the scan mirror.

5. The system of claim 2, wherein the driver comprises a piezoelectric transducer.

6. The system of claim 2 wherein the scan mirror oscillates at a rate of at least 500 Hz.

7. The system of claim 2 wherein the scan mirror oscillates at a rate of at least 1000 Hz.

8. The system of claim 2 wherein a translational movement of the scan mirror results in a proportionally longer depth extension of a pseudo-projection image sensed by the light sensor.

9. The system of claim 1 wherein the variable power element (VPE) comprises:

a first VPE lens and a second VPE lens, where the second VPE lens includes a scanning lens connected to a drive, wherein movement of the second VPE lens operates to translate the second VPE lens by a scanning distance Δ

to scan focal plans in the carrier.

10. The system of claim 1 wherein the variable power element (VPE) comprises a variable focal lens.

11. The system of claim 10 wherein the variable focal lens comprises a transparent cell containing at least two non-miscible fluids.

12. The system of claim 11 wherein the variable focal lens varies optical power in response to a voltage source control.

13. The system of claim 1 wherein the microscope objective lens includes an exit pupil E and the variable power element (VPE) has a VPE entrance pupil E′

comprises a beamsplitter, a scan mirror and a scan lens having an entrance pupil which is coincident with the VPE entrance pupil, where the exit pupil E is focused to be coincident with the entrance pupil E′ and

the beamsplitter, the scan mirror and the scan lens are aligned along an optical path with the microscope objective lens, and wherein the scan mirror is controlled by a drive.

14. The system of claim 13 further comprising an optical relay between the microscope objective lens and the variable power element.

15. The system of claim 14 wherein translating the scan mirror a distance Δ

z′

produces a focus shift Δ

z at the object equal to 2 Δ

z′

n/(n′

m_T²), where n is the object space index of refraction, n′

is the scanner space index of refraction, m_T is the transverse magnification between an object and the scan mirror.

16. The system of claim 2 wherein the drive comprises a piezoelectric actuator.

17. The system of claim 2 wherein the scan mirror and drive comprise a micro-electro-mechanical-systems flexure with a reflective coating.

18. The system of claim 2 wherein the scan mirror and drive comprise a metal mirror with a solenoid actuator.

19. The system of claim 2 wherein the driver comprises an acoustic wave generator driving a reflective elastic diaphragm.

20. The system of claim 2 wherein the scan lens has an NA at least equal to the microscope objective lens NA divided by the transverse magnification m_T between the object and scan mirror.

21. The system of claim 20 wherein the scan lens comprises a telecentric lens.

22. The system of claim 1 wherein the carrier comprises an optically transparent capillary tube.

23. The system of claim 1 wherein the carrier is coupled to a rotational motor.

24. The system of claim 1 wherein the object is moved relatively to the light sensor to present multiple views for producing at least one image of the at least one feature of interest at each view.

25. The system of claim 1 wherein the object of interest comprises a biological cell.

26. The system of claim 1 wherein the light sensor comprises a detector selected from the group consisting of charge coupled devices, complementary metal-oxide-semiconductor devices, solid-state image sensors, and solid-state image sensor detector arrays.

27. The system of claim 1, wherein the object-containing tube has a diameter of at least 50 microns.

28. The system of claim 2, wherein the drive comprises a piezoelectric transducer.

29. The system of claim 2 wherein the scan mirror oscillates at a rate of at least 500 Hz.

30. The system of claim 2 wherein the scan mirror oscillates at a rate of at least 1000 Hz.

31. The system of claim 1 wherein a translational movement of the scan mirror results in a proportionally longer depth extension of a pseudo-projection image sensed by the light sensor.

32. An optical projection tomography method for imaging an object of interest, the optical projection tomography method comprising:

illuminating at least part of the object of interest within the field of view of a microscope objective lens located to receive light passing through the object of interest;

transmitting light through the microscope objective lens to impinge upon a variable power element;

driving the variable power element with respect to the microscope objective lens to scan through multiple focal planes in the object of interest; and

sensing light transmitted from the variable power element.

33. The method of claim 32 wherein driving the variable power element comprises oscillating a scan mirror along an optical path such that the reflecting surface remains perpendicular to the optical path whereby the oscillating scan mirror scans through a plurality of focal planes in the carrier.

34. The method of claim 32 wherein transmitting light comprises imaging a microscope objective lens exit pupil onto a scan lens entrance pupil.

35. The method of claim 33 wherein the scan mirror oscillates at a rate of at least 500 Hz.

36. The method of claim 33 wherein the scan mirror oscillates at a rate of at least 1000 Hz.

37. The method of claim 33 wherein driving the variable power element comprises translating a lens by a scanning distance Δ

to scan focal plans in the object of interest.

38. The method of claim 33 wherein driving the variable power element comprises applying varying voltages to the variable power element.

39. The method of claim 33 wherein driving the variable power element comprises translating a scan mirror a distance Δ

z′

to produces a focus shift Δ

z at the object equal to 2 Δ

z′

/n/(n′

m_T²), where n is the object space index of refraction, n′

is the scanner space index of refraction, m_T is the transverse magnification between the object of interest and the scan mirror.

40. The method of claim 33 further comprising holding the object of interest in a carrier, and rotating the carrier.

41. The method of claim 33 further comprising moving the object of interest relatively to the light sensor to present multiple views.

42. The method of claim 33 the object of interest comprises a biological cell.

43. An optical projection tomography system for imaging an object of interest, the optical projection tomography method comprising:

means for illuminating at least part of the object of interest within the field of view of a microscope objective lens located to receive light passing through the object of interest;

means for transmitting light through the microscope objective lens to impinge upon a variable power element;

means for driving the variable power element with respect to the microscope objective lens to scan through multiple focal planes in the object of interest; and

means for sensing light transmitted from the variable power element.