Illumination apparatus optimized for synthetic aperture optics imaging using minimum selective excitation patterns

• US 9,465,228 B2
• Filed: 03/19/2010
• Issued: 10/11/2016
• Est. Priority Date: 03/19/2010
• Status: Active Grant

• Current Assignee: Rebus Biosystems, Inc.
• Original Assignee: Optical Biosystems Incorporated
• Inventors: Lee, Chun-Sheu, Park, Jong Buhm
• Primary Examiner(s): ELAHI, SHAN E
• Application Number:
  US12/728,140
• Publication Number:
  US 20110228073A1
• Time in Patent Office: 2,398 Days
• Field of Search: 348/80, 348/79, 250/311
• US Class Current: 1/1
• CPC Class Codes: G02B 21/06 Means for illuminating specimens
• CPC Class Codes: G02B 21/18 Arrangements with more than one light path, e.g. for comparing two specimens
• CPC Class Codes: G02B 21/367 providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison
• CPC Class Codes: G02B 27/58 Optics for apodization or superresolution; Optical synthetic aperture systems
• CPC Class Codes: G06T 2207/10056 Microscopic image
• CPC Class Codes: G06T 2207/30072 Microarray; Biochip, DNA array; Well plate
• CPC Class Codes: G06T 5/00 Image enhancement or restoration
• CPC Class Codes: G06T 5/50 using two or more images, e.g. averaging or subtraction
• CPC Class Codes: G06T 7/0012 Biomedical image inspection
• CPC Class Codes: G06V 20/693 Acquisition
• CPC Class Codes: G06V 20/695 Preprocessing, e.g. image segmentation

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

a plurality of interference pattern generation modules (IPGMs), each IPGM configured to generate a pair of light beams that interfere to generate a selective excitation pattern on the target at a predetermined orientation and a predetermined pitch;

a monolithic half-ring shaped structure holding the plurality of IPGMs; and

an optical imaging module configured to optically image the illuminated target at a resolution insufficient to resolve the objects, the optical image of the illuminated target being further processed using information on the selective excitation pattern to obtain a final image of the illuminated target at a resolution sufficient to resolve the objects.

2. The apparatus of claim 1, wherein the number of IPGMs is equal to the number of selective excitation patterns used for performing SAO on the target.

3. The apparatus of claim 1, wherein the IPGMs are placed substantially symmetrically around the half-ring shape.

4. The apparatus of claim 1, wherein at least one of the IPGMs includes:

a beam splitter for splitting a first laser beam into the pair of laser beams including a second laser beam and a third laser beam;

a first mirror reflecting the second laser beam onto the target;

a second mirror reflecting the third laser beam; and

a modulator configured to modulate an optical path length of the third laser beam reflected by the second mirror, and

wherein the reflected second laser beam and the reflected, modulated third laser beam interfere to generate the selective excitation on the target.

5. The apparatus of claim 1, wherein at least one of the IPGMs includes:

a beam splitter for splitting a first laser beam into the pair of laser beams including a second laser beam and a third laser beam;

a first mirror reflecting the second laser beam;

a second mirror further reflecting the second laser beam onto the target;

a third mirror reflecting the third laser beam; and

a modulator configured to modulate an optical path length of the third laser beam reflected by the third mirror, and

wherein the second laser beam and the third laser beam travel substantially equal path lengths before interfering with each other on the target to generate the selective excitation pattern.

6. An apparatus for performing synthetic aperture optics (SAO) on a target including one or more objects, the apparatus comprising:

a plurality of interference pattern generation modules (IPGMs), each IPGM configured to generate a pair of light beams that interfere to generate a selective excitation pattern on the target at a predetermined orientation and a predetermined pitch, the number of IPGMs being equal to the number (N) of selective excitation patterns used for performing SAO on the target, and the number (N) of selective excitation patterns corresponding 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 a width of a detected area (w) captured by a pixel of the optical imaging module;

a monolithic half-ring shaped structure holding the plurality of IPGMs; and

an optical imaging module configured to optically image the illuminated target at a resolution insufficient to resolve the target, the optical image of the illuminated target being further processed using information on the selective excitation patterns to obtain a final image of the illuminated target at a resolution sufficient to resolve the target.

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

8. The apparatus of claim 6, wherein the IPGMs are placed substantially symmetrically around the half-ring shape.

9. The apparatus of claim 6, wherein at least one of the IPGM includes:

a beam splitter for splitting a first laser beam into the pair of laser beams including a second laser beam and a third laser beam;

a first mirror reflecting the second laser beam onto the target;

a second mirror reflecting the third laser beam; and

a modulator configured to modulate an optical path length of the third laser beam reflected by the second mirror, and

wherein the reflected second laser beam and the reflected, modulated third laser beam interfere to generate the selective excitation on the target.

10. The apparatus of claim 6, wherein at least one of the IPGM includes:

a beam splitter for splitting a first laser beam into the pair of laser beams including a second laser beam and a third laser beam;

a first mirror reflecting the second laser beam;

a second mirror further reflecting the second laser beam onto the target;

a third mirror reflecting the third laser beam; and

a modulator configured to modulate an optical path length of the third laser beam reflected by the third mirror, and

wherein the second laser beam and the third laser beam travel substantially equal path lengths before interfering with each other on the target to generate the selective excitation pattern.