Synthetic aperture optics imaging method using minimum selective excitation patterns

• US 8,502,867 B2
• Filed: 03/19/2010
• Issued: 08/06/2013
• Est. Priority Date: 03/19/2010
• Status: Active Grant

• Current Assignee: Rebus Biosystems, Inc.
• Original Assignee: LightSpeed Genomics, Inc.
• Inventors: Park, Jong Buhm
• Primary Examiner(s): Dastouri, Mehrdad
• Assistant Examiner(s): WALKER, JARED T
• Application Number:
  US12/728,110
• Publication Number:
  US 20110228068A1
• Time in Patent Office: 1,236 Days
• Field of Search: 348/135, 348/79, 348/80
• US Class Current: 348/135
• CPC Class Codes: G01N 15/1434 Optical arrangements
• CPC Class Codes: G01N 2015/145 by pattern of light, e.g. fringe pattern
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 2201/0635 Structured illumination, e.g. with grating

Abstract

A synthetic aperture optics (SAO) imaging method minimizes the number of selective excitation patterns used to illuminate the imaging target, based on the objects'"'"' physical characteristics corresponding to spatial frequency content from the illuminated target and/or one or more parameters of the optical imaging system used for SAO. With the minimized number of selective excitation patterns, the time required to perform SAO is reduced dramatically, thereby allowing SAO to be used with DNA sequencing applications that require massive parallelization for cost reduction and high throughput. In addition, an SAO apparatus optimized to perform the SAO method is provided. The SAO apparatus includes a plurality of interference pattern generation modules that can be arranged in a half-ring shape.

Claims

1. A method for performing synthetic aperture optics (SAO) on a target including one or more objects, the method comprising the steps of:

illuminating the target with a predetermined number (N) of selective excitation patterns, wherein the set of N selective excitation patterns results from a design process using a minimum distance (Δ

x) between objects to be resolved by SAO and a width of a detected area (w) captured by a pixel of a system for said optical imaging, wherein the number (N) of selective excitation patterns is substantially determined from;

N=floor(L/2)

wherein L is the number of k-space sample points in the k-space, and floor ( ) rounds the number to the nearest but smaller integer; and

L=round((PFOV/Δ

x)²)

wherein round ( ) rounds the number to the nearest integer, and PFOV is the extent in the reciprocal space of the k-space to be reconstructed from the samples;

optically imaging the illuminated target at a resolution insufficient to resolve the objects; and

processing optical images of the illuminated target using information on the selective excitation patterns to obtain a final image of the illuminated target at a resolution sufficient to resolve the objects.

2. The method of claim 1, wherein the number (N) of selective excitation patterns corresponds to the number of k-space sampling points in a k-space sampling space in a frequency domain, an extent of the k-space sampling space being substantially proportional to an inverse of the minimum distance (Δ

x) between the objects that is to be resolved by SAO, and an inverse of a k-space sampling interval between the k-space sampling points being less than the width of a detected area (w) captured by a pixel of a system for said optical imaging.

3. The method of claim 2, further comprising removing aliasing in the final image caused as a result of using said inverse of the k-space sampling interval less than the width of the detected area (w) captured by the pixel of said optical imaging system.

4. The method of claim 1, further comprising removing effects of apodization caused by a weighting function of a system for said optical imaging, said weighting function corresponding to a convolution of a pixel sensitivity function of a pixel of said optical imaging system for detecting light from the illuminated target and a point-spread function of a lens through which said light is passed through in said optical imaging system.

5. The method of claim 1, wherein the number (N) of selective excitation patterns is determined based upon at least one of a plurality of parameters of a system for said optical imaging, including a width (w) of a detected area captured by a pixel of said optical imaging system, a wavelength of light from the illuminated target, and a numerical aperture of a lens through which said light is passed through in said optical imaging system.

6. The method of claim 1, wherein the number (N) of selective excitation patterns corresponds to non-uniformly selected ones of the k-space sampling points.

7. The method of claim 1, wherein the target is illuminated with two phases of each one of the selective excitation patterns and another phase of only one of the selective excitation patterns, said another phase being different from the two phases.

8. The method of claim 1, wherein the target is illuminated with three phases of each one of the selective excitation patterns.

9. The method of claim 1, wherein the objects include nucleic acid microparticles.

20. The method of claim 1, wherein N=12 and L=25.

21. The method of claim 1, further comprising further reducing the number of k-space sampling points.

22. The method of claim 21, wherein the number (N) of selective excitation patterns corresponds to sparse k-space sampling points.

23. The method of claim 1, wherein the selective excitation patterns correspond to the k-space sampling points within a circular region.

10. A system for performing synthetic aperture optics (SAO) on a target including one or more objects, the system comprising:

a plurality of illumination modules configured to illuminate the target with a predetermined number (N) of selective excitation patterns, wherein the set of N selective excitation patterns results from a design process using a minimum distance (Δ

x) between objects to be resolved by SAO and a width of a detected area (w) captured by a pixel of a system for said optical imaging, wherein the number (N) of selective excitation patterns is substantially determined from;

N=floor(L/2)

wherein L is the number of k-space sample points in the k-space, and floor ( ) rounds the number to the nearest but smaller integer; and

L=round((PFOV/Δ

x)²)

wherein round ( ) rounds the number to the nearest integer, and PFOV is the extent in the reciprocal space of the k-space to be reconstructed from the samples;

an optical imaging module configured to optically image the illuminated target at a resolution insufficient to resolve the objects; and

a SAO processing module configured to process the optical images of the illuminated target using information on the selective excitation patterns to obtain a final image of the illuminated target at a resolution sufficient to resolve the objects.

11. The system of claim 10, wherein the number (N) of selective excitation patterns corresponds to the number of k-space sampling points in a k-space sampling space in a frequency domain, an extent of the k-space sampling space being substantially proportional to an inverse of the minimum distance (Δ

x) between the objects that is to be resolved by SAO and an inverse of a k-space sampling interval between the k-space sampling points being less than the width of a detected area (w) captured by a pixel of the optical imaging module.

12. The system of claim 11, wherein the SAO processing module is further configured to remove aliasing in the final image caused as a result of using said inverse of the k-space sampling interval less than the width of the detected area (w) captured by the pixel of the optical imaging module.

13. The system of claim 10, wherein the SAO processing module is further configured to remove effects of apodization caused by a weighting function of the optical imaging module, said weighting function corresponding to a convolution of a pixel sensitivity function of a pixel of said optical imaging module for detecting light from the illuminated target and a point-spread function of a lens through which said light is passed through in said optical imaging module.

14. The system of claim 10, wherein the number (N) of selective excitation patterns is determined based upon at least one of a plurality of parameters of said optical imaging module, including a width (w) of a detected area captured by a pixel of said optical imaging module, a wavelength of the light from the illuminated target, and a numerical aperture of a lens through which said light is passed through in said optical imaging module.

15. The system of claim 10, wherein the number (N) of selective excitation patterns corresponds to non-uniformly selected ones of the k-space sampling points.

16. The system of claim 10, wherein the target is illuminated with two phases of each one of the selective excitation patterns and another phase of only one of the selective excitation patterns, said another phase being different from the two phases.

17. The system of claim 10, wherein the target is illuminated with three phases of each one of the selective excitation patterns.

18. The system of claim 10, wherein the objects include nucleic acid microparticles.

19. The system of claim 10, wherein each illumination module generates one of the selective excitation patterns for illuminating the target.

24. The system of claim 10, wherein N=12 and L=25.

25. The system of claim 10, wherein the number of k-space sampling points is further reduced.

26. The system of claim 25, wherein the number (N) of selective excitation patterns corresponds to sparse k-space sampling points.

27. The system of claim 10, wherein the selective excitation patterns correspond to the k-space sampling points within a circular region.