# US 2025/0085191 A1 · 3D Refractive Index Estimation Based on Partially-Coherent Optical Diffraction Tomography (PC-ODT) and Deep Learning

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- Number: US 2025/0085191 A1
- Document ID: US20250085191A1
- Status: Published application
- Kind: A1
- Application number: 18/225,100
- Filed: 2023-07-21
- Published: 2025-03-13
- Earliest claimed: 2022-07-24
- Inventors: George Nehmetallah
- Web page: https://patentgrep.com/patent/US20250085191A1

## CPC

- G01M 11/0228: {by measuring refractive power}
- G01M 11/0207: {Details of measuring devices}
- G02B 21/06: Means for illuminating specimens
- G02B 21/08: Condensers
- G02B 21/14: affording illumination for phase-contrast observation
- G02F 1/294: {Variable focal length devices}
- G01M: TESTING STATIC OR DYNAMIC BALANCE OF MACHINES OR STRUCTURES; TESTING OF STRUCTURES OR APPARATUS, NOT OTHERWISE PROVIDED FOR
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02F: OPTICAL DEVICES OR ARRANGEMENTS FOR THE CONTROL OF LIGHT BY MODIFICATION OF THE OPTICAL PROPERTIES OF THE MEDIA OF THE ELEMENTS INVOLVED THEREIN; NON-LINEAR OPTICS; FREQUENCY-CHANGING OF LIGHT; OPTICAL LOGIC ELEMENTS; OPTICAL ANALOGUE/DIGITAL CONVERTERS

## Abstract

A system, a microscope, and a method for determining a three dimensional refractive index are provided. The system comprises an illumination system configured to generate an illumination beam to illuminate a target at a plurality of illumination angles; an optical system to direct the illumination beam to the target; a refocusing system positioned in a detection path and configured to perform stageless axial refocusing of a measurement beam, a detection system configured to capture an intensity stack for the plurality of illumination angles and during the axial refocusing; and a processor configured to generate a three dimensional refractive index of the target based on the intensity stack. The measurement beam is transmitted through the target.

## Claims

### Claim 1

A system comprising:
an illumination system configured to generate an illumination beam to illuminate a target at a plurality of illumination angles;
an optical system to direct the illumination beam to the target;
a refocusing system positioned in a detection path and configured to perform stageless axial refocusing of a measurement beam, wherein the measurement beam is transmitted through the target;
a detection system configured to capture an intensity stack for the plurality of illumination angles and during the axial refocusing; and
a processor configured to generate a three dimensional refractive index of the target based on the intensity stack.

### Claim 2 (depends on 1)

The system of claim 1, wherein the illumination system comprises a light emitting diode (LED) dome array and wherein the LED dome array comprises a plurality of LEDs.

### Claim 3 (depends on 2)

The system of claim 2, wherein each LED of the LED dome array is individually controlled; and
wherein an illumination time of each respective LED is controlled by the processor during measurement.

### Claim 4 (depends on 3)

The system of claim 3, wherein two or more LEDs are simultaneously activated during measurement to increase a throughput of the system.

### Claim 5 (depends on 1)

The system of claim 1, wherein the illumination beam is partially coherent.

### Claim 6 (depends on 1)

The system of claim 1, wherein the optical system comprises an objective lens.

### Claim 7 (depends on 1)

The system of claim 1, wherein the refocusing system comprises, a divergent offset lens and an electronically tunable lens.

### Claim 8 (depends on 7)

The system of claim 7, wherein the refocusing system does not comprise moving mechanical parts.

### Claim 9 (depends on 7)

The system of claim 7, wherein the refocusing system further comprises a relay lens system; and
wherein the offset lens and the electronically tunable lens are positioned in the detection path at a focal plane of the relay lens system.

### Claim 10 (depends on 1)

The system of claim 1, wherein the three dimensional refractive index is generated using a trained neural network model, and wherein the intensity stack is an input to the trained neural network model.

### Claim 11 (depends on 1)

The system of claim 1, wherein training the neural network model comprises:
generating intensity patterns through propagating illumination beams at the plurality of illumination angles through a sample and at a plurality of focus length of the refocusing system; and
reconstructing the respective three dimensional refractive index using a gradient based technique.

### Claim 12 (depends on 11)

The system of claim 11, wherein the intensity patterns are generated through a simulation of the system and wherein the sample is a phantom.

### Claim 13 (depends on 11)

The system of claim 11, wherein the neural network model is trained using biological samples.

### Claim 14 (depends on 1)

The system of claim 1, wherein the intensity stack represents a plurality of intensity images captured by the detection system for the plurality of illumination angles and for a plurality of focus length of the refocusing system.

### Claim 15

A digital microscope comprising:
an illumination system configured to generate an illumination beam to illuminate a target at a plurality of illumination angles;
an optical system to direct the illumination beam to the target;
a refocusing system positioned in a detection path and configured to perform stageless axial refocusing of a measurement beam, wherein the measurement beam is transmitted through the target;
a detection system configured to capture an intensity stack for the plurality of illumination angles and during the axial refocusing; and
a processor configured to generate a three dimensional refractive index of the target based on the intensity signal.

### Claim 16 (depends on 15)

The digital microscope of claim 15, wherein the refocusing system comprises a divergent offset lens and an electronically tunable lens.

### Claim 17 (depends on 16)

The digital microscope of claim 16, wherein the electronically tunable lens is a tunable liquid crystal lens.

### Claim 18 (depends on 16)

The digital microscope of claim 16, wherein the refocusing system does not comprise moving mechanical parts.

### Claim 19

A method for determining a three dimensional refractive index of a target, comprising
illuminating the sample at a plurality of illumination angles using an partially incoherent beam;
performing stageless axial refocusing of a measurement beam, wherein the measurement beam is transmitted through the target;
capturing an intensity stack for the plurality of illumination angles and during the axial refocusing; and
generating the three dimensional refractive index of the target using a trained neural network.

### Claim 20 (depends on 16)

The method of claim 16, wherein training the neural network comprises:
generating intensity patterns through propagating illumination beams at the plurality of illumination angles through a sample and at a plurality of focus length of the refocusing system; and
reconstructing the respective three dimensional refractive index using a gradient based technique.
