# US 10,871,745 B2 · Device and method for iterative phase recovery based on pixel super-resolved on-chip holography

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- Number: US 10,871,745 B2
- Document ID: US10871745B2
- Status: Granted
- Kind: B2
- Application number: 15/500,880
- Filed: 2015-07-31
- Published: 2017-08-03
- Granted: 2020-12-22
- Earliest claimed: 2014-08-01
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Aydogan Ozcan; Alon Greenbaum; Yibo Zhang; Alborz Feizi; Wei Luo
- Web page: https://patentgrep.com/patent/US10871745B2

## CPC

- G03H 1/0005: {Adaptation of holography to specific applications (holographic optical element G02B5/32; holographic scanner G02B26/106; recognition using holographic mask G06V10/88; holographic memories G11B7/0065, G11C13/042)}
- G01N 15/1429: Signal processing
- G01N 15/1433: using image recognition
- G01N 15/1434: Optical arrangements
- G03H 1/0443: {Digital holography, i.e. recording holograms with digital recording means (holobject computation G03H1/0866)}
- G03H 1/0866: {Digital holographic imaging, i.e. synthesizing holobjects from holograms}
- G03H 1/0891: {Processes or apparatus adapted to convert digital holographic data into a hologram (G03H1/2294 takes precedence)}
- H04N 23/56: provided with illuminating means
- H04N 23/698: for achieving an enlarged field of view, e.g. panoramic image capture
- G01N 2015/1006: {for cytology}
- G01N 2015/144: {Imaging characterised by its optical setup}
- G01N 2015/1445: {Three-dimensional imaging, imaging in different image planes, e.g. under different angles or at different depths, e.g. by a relative motion of sample and detector, for instance by tomography}
- G01N 2015/1454: {using phase shift or interference, e.g. for improving contrast}
- G03H 2001/005: {in microscopy, e.g. digital holographic microscope [DHM]}
- G03H 2001/0447: {In-line recording arrangement}
- G03H 2001/0454: {Arrangement for recovering hologram complex amplitude}
- G03H 2001/046: {Synthetic aperture}
- G03H 2001/0816: {Iterative algorithms}
- G03H 2001/0883: {Reconstruction aspect, e.g. numerical focusing}
- G03H 2001/2655: {Time multiplexing, i.e. consecutive records wherein the period between records is pertinent per se}
- G03H 2210/42: from real object, e.g. using 3D scanner
- G03H 2226/02: Computing or processing means, e.g. digital signal processor [DSP]
- G03H 2227/03: Means for moving one component (G03H1/0476, G03H2001/2695 take precedence)
- G03H: HOLOGRAPHIC PROCESSES OR APPARATUS (holograms, e.g. point holograms, used as ordinary optical elements G02B5/32; producing stereoscopic or other three-dimensional effects G02B30/00; diffraction-grating systems G02B27/44; systems using moiré fringes G02B27/60; optical logic elements G02F3/00; stereo-photography G03B35/00; photosensitive materials or processes for photographic purposes G03C; {stereo-photographic or similar processes G03C9/00}; apparatus for processing exposed photographic materials G03D; analogue computers performing mathematical operations with the aid of optical elements G06E3/00; authentication by radiation, of concealed information carried by holograms or diffraction gratings G06K19/16; holographic storage G11B7/0065, G11C13/04; {stereoscopic or other three dimensional effects in television systems H04N13/00})
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- H04N: PICTORIAL COMMUNICATION, e.g. TELEVISION

## Abstract

A method for lens-free imaging of a sample or objects within the sample uses multi-height iterative phase retrieval and rotational field transformations to perform wide FOV imaging of pathology samples with clinically comparable image quality to a benchtop lens-based microscope. The solution of the transport-of-intensity (TIE) equation is used as an initial guess in the phase recovery process to speed the image recovery process. The holographically reconstructed image can be digitally focused at any depth within the object FOV (after image capture) without the need for any focus adjustment, and is also digitally corrected for artifacts arising from uncontrolled tilting and height variations between the sample and sensor planes. In an alternative embodiment, a synthetic aperture approach is used with multi-angle iterative phase retrieval to perform wide FOV imaging of pathology samples and increase the effective numerical aperture of the image.

## Claims

### Claim 1

A method for lens-free imaging of a pathology sample or objects within the sample comprising:
a) illuminating a sample located a distance z1 away from a light source;
b) obtaining a first plurality of images of the sample with an image sensor disposed a distance z2 away from the sample, wherein z1>>z2, wherein the plurality of images are obtained by changing the relative position of the light source, image sensor, or sample in lateral shifts;
c) adjusting the distance z2;
d) obtaining an additional plurality of images of the sample at the adjusted distance z2, wherein the additional plurality of images at the adjusted distance z2 are obtained by changing the relative position of the light source, image sensor, or sample in lateral shifts;
e) repeating operations c) and d) a plurality of times;
f) generating a high-resolution pixel super-resolved hologram at each distance z2 from the first plurality of images and the additional plurality of images at the adjusted distance z2;
g) recovering lost phase information of the high-resolution pixel super-resolved hologram at a given z2 distance comprising:
1) analytically computing an initial phase estimate at the given distance z2 based on first and second measurements of the high-resolution pixel super-resolved hologram(s);
2) updating the phase estimate from (1) using propagation of an estimate of a complex optical wave at the given distance z2 to a modified or adjusted z2 distance, which generates new amplitude and phase information for the propagated complex wave;
3) applying 3D transformation matrices to the propagated complex wave to correct for relative tilt in the z direction between the sample and the image sensor, wherein the application of the 3D transformation matrices generates a tilted guess, the tilted guess being registered to a measured hologram and averaging the tilted guess amplitude with a measured amplitude to generate updated amplitude followed by rotation back to a plane parallel to the image sensor;
4) wherein at the modified or adjusted z2 distance, the updated amplitude of the super-resolved hologram replaces the currently computed amplitude information of the propagated complex wave from (2) and the new phase information is retained for next iterations;
5) propagating the complex estimated wave to reach a further modified or adjusted z2 distance;
6) repeating steps 3) through 5) among all or a sub-set of measured planes corresponding to different z2 distances as a loop until convergence is achieved; and
h) outputting a phase-recovered complex field at an object plane based on the recovered lost phase information obtained in g) for one or more z2 planes.

### Claim 2 (depends on 1)

The method of claim 1, wherein the initial phase estimate consists of an analytically computed estimate using an unmodified transport-of-intensity equation (TIE).

### Claim 3 (depends on 1)

The method of claim 1, wherein the method is performed using one or more Graphic Processing Units (GPUs).

### Claim 4 (depends on 1)

The method of claim 1, wherein the loop comprises a sequential loop.

### Claim 5 (depends on 1)

The method of claim 1, wherein the loop comprises a random loop.

### Claim 6 (depends on 1)

The method of claim 1, wherein the 3D rotation transformation matrices are determined by local tilt angles in the z direction, which are determined by one or more autofocusing operations performed at one or more positions within the sample comprising digitally propagating images at different image planes and calculating a sharpness measure for each image.

### Claim 7 (depends on 1)

The method of claim 1, wherein the light source comprises a single-color light source and further comprising pseudo-coloring a reconstructed image from the phase-recovered complex field, wherein the pseudo-coloring comprises applying a learned mapping function to map pixel luminance (Y) in a YUV color space to color channels (U, V) in YUV color space followed by conversion to a RGB color space for pixels of the reconstructed image.

### Claim 8 (depends on 1)

A system for carrying out the method of claim 1, comprising one or more processors configured to execute instructions thereon for recovering an object image based on the high-resolution pixel super-resolved hologram at each z2 distance.

### Claim 9 (depends on 1)

The method of claim 1, wherein outputting a phase-recovered complex field at an object plane based on the recovered lost phase information for one or more z2 planes comprises displaying an image of the sample or objects within the sample on a display.

### Claim 10 (depends on 1)

The method of claim 1, wherein the pathological tissue sample comprises a stained tissue sample.

### Claim 11 (depends on 1)

The method of claim 1, wherein a moveable stage adjusts the distance z2 by moving the sample or the image sensor.