Methods and systems for three dimensional optical imaging, sensing, particle localization and manipulation

• US 9,538,157 B2
• Filed: 08/21/2014
• Issued: 01/03/2017
• Est. Priority Date: 04/09/2010
• Status: Active Grant

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Piestun, Rafael, Quirin, Sean Albert
• Primary Examiner(s): Li, Ruiping
• Application Number:
  US14/465,543
• Publication Number:
  US 20150035946A1
• Time in Patent Office: 866 Days
• Field of Search: 382/154, 382274-275
• US Class Current: 1/1
• CPC Class Codes: G06T 2207/10056 Microscopic image
• CPC Class Codes: G06T 2207/10064 Fluorescence image
• CPC Class Codes: G06T 7/77 using statistical methods
• CPC Class Codes: H04N 13/204 using stereoscopic image cameras stereoscopic photography G03B35/00

Abstract

Embodiments include methods, systems, and/or devices that may be used to image, obtain three-dimensional information from a scene, and/or locate multiple small particles and/or objects in three dimensions. A point spread function (PSF) with a predefined three dimensional shape may be implemented to obtain high Fisher information in 3D. The PSF may be generated via a phase mask, an amplitude mask, a hologram, or a diffractive optical element. The small particles may be imaged using the 3D PSF. The images may be used to find the precise location of the object using an estimation algorithm such as maximum likelihood estimation (MLE), expectation maximization, or Bayesian methods, for example. Calibration measurements can be used to improve the theoretical model of the optical system. Fiduciary particles/targets can also be used to compensate for drift and other type of movement of the sample relative to the detector.

Claims

1. An imaging system for three dimensional localization, imaging, and/or tracking of an object, the imaging system comprising:

an optical system comprising an objective lens, wherein the optical system produces a spatially varying phase difference imposed among different components of the light coming through different parts of the objective lens to generate a three dimensional point spread function image, wherein a maximum of the point spread function describes a curve in three-dimensional space;

at least one sensor array configured to receive one or more images of an object through the optical system; and

a processing module configured to provide one or more of the following functions imaging of the object, axial ranging of the object, a three dimensional estimate of a position of the object, and tracking of the object.

2. The imaging system according to claim 1, wherein the optical system includes multiple channels that each generate a different three dimensional point spread function.

3. The imaging system according to claim 1, wherein the maximum of the point spread function describes a curve in three-dimensional space that turns around an axis with a varying offset from the axis.

4. The imaging system according to claim 1, wherein the maximum of the point spread function describes a helix in three-dimensional space with varying offset and pitch.

5. The imaging system according to claim 1, wherein the maximum of the point spread function describes a curve in three-dimensional space that is similar to a helix.

6. The imaging system according to claim 1, wherein the maximum of the point spread function describes a curve in three-dimensional space with varying offset from an axis.

7. The imaging system according to claim 1, wherein the maximum of the point spread function describes a curve in three-dimensional space with varying offset and/or varying pitch.

8. The imaging system according to claim 7, wherein the point spread function describes a helical curve.

9. The imaging system according to claim 1, wherein the point spread function describes a helical curve when one or both of the axis and offset are constant.

10. The imaging system according to claim 1, wherein the processing module is further configured to produce a spatially varying phase delay with a refractive, reflective, or diffractive optical element.

11. The imaging system according to claim 1, wherein the processing module is further configured to produce either or both an extended depth of field of the object and a depth map of the object.

12. The imaging system according to claim 1, wherein the processing module is configured to provide one or more of the following functions imaging of the object, axial ranging of the object, a three dimensional estimate of a position of the object, and tracking of the object.

13. The imaging system according to claim 1, further comprising a point spread function that produces a modulation transfer function with minimal zeros.

14. The imaging system according to claim 1, wherein the processing module is further configured to wide-field image.

15. The imaging system according to claim 1, wherein the optical system includes at least portions of a standard microscope.

16. A method comprising:

providing one or more optical elements, wherein in at least one of the one or more optical elements provides phase modulation;

passing light through at least one of the one or more optical elements toward an object;

detecting light from the object through at least one of the one or more optical elements with a light detection system,

modifying the light received at the light detection system to create a point spread function at an optical detection plane, wherein a maximum of the point spread function describes a curve in three-dimensional space; and

estimating a distance to the object using the point spread function.

17. The method according to claim 16, wherein at least one of the one or more optical elements comprises one or more optical elements selected from the list consisting of a lens, phase mask, a hologram, spatial light modulator, and a non-flat reflective surface.

18. The method according to claim 16, further comprising tracking the object.

19. The method according to claim 16, further comprising estimating a range to the object.