# US 2019/0170695 A1 · System and Method for Nanoscale Photoacoustic Tomography

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- Number: US 2019/0170695 A1
- Document ID: US20190170695A1
- Status: Published application
- Kind: A1
- Application number: 16/088,770
- Filed: 2017-03-31
- Published: 2019-06-06
- Earliest claimed: 2016-04-01
- Assignees: The Board of Regents of the University of Oklahoma
- Applicants: The Board of Regents of the University of Oklahoma
- Inventors: Liangzhong Xiang; Jian Chen; Pratik Samant
- Web page: https://patentgrep.com/patent/US20190170695A1

## CPC

- G01N 29/0672: {by acoustic tomography (medical tomography A61B8/13)}
- A61B 5/0095: {by applying light and detecting acoustic waves, i.e. photoacoustic measurements}
- A61B 5/02007: {Evaluating blood vessel condition, e.g. elasticity, compliance}
- G01N 21/1702: {with opto-acoustic detection, e.g. for gases or analysing solids}
- G01N 29/221: {Arrangements for directing or focusing the acoustical waves (electronic orientation or focusing G01N29/262; sound directing or focusing G10K11/26; mechanical steering of sound transducers or their beams G10K11/35)}
- G01N 29/223: {Supports, positioning or alignment in fixed situation (mounting transducers per se G10K11/004)}
- G01N 29/2418: {using optoacoustic interaction with the material, e.g. laser radiation, photoacoustics (photoacoustic cells G01N21/1702; measuring characteristics of vibrations by using radiation-sensitive means G01H9/00; acousto-optical conversion techniques for short-range imaging G01S15/8965; sound-producing devices using laser bundle G10K15/046)}
- A61B 8/13: Tomography (A61B8/10, A61B8/12 take precedence)
- A61B 2562/0285: Nanoscale sensors
- G01N 2021/1706: {in solids}
- G01N 2201/06113: Coherent sources; lasers
- G01N 2291/02466: Biological material, e.g. blood
- 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)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

A method and system of nanoscale photoacoustic tomography (nPAT) for non-invasive three-dimensional mapping and characterization of fine cellular structures (such as but not limited to organelles, vesicles, and macromolecules) of biological samples is disclosed.

## Claims

### Claim 1

A nanoscale photoacoustic tomography system comprising:
an ultrafast pulse laser system configured to:
provide a generation beam for generating photoacoustic waves in a biological sample; and
provide a probe beam for assessing changes in light reflectivity in the biological sample caused by the photoacoustic waves;
a scanning stage configured to mount the biological sample for analysis;
a first focusing assembly configured to focus the generation beam on the biological sample;
a second focusing assembly configured to:
focus the probe beam on the biological sample; and
collect backscattered light reflected from the biological sample;
an optical detector configured to:
sense the backscattered light; and
emit signals in response to the backscattered light; and
a processor configured to record and process the signals.

### Claim 2 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, wherein the generation beam and/or the probe beam provided by the ultrafast pulse laser system has a pulse duration in a range of about 100 femtoseconds (fs) to about 100 picoseconds (ps).

### Claim 3

(canceled)

### Claim 4 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, wherein the first focusing assembly comprises a first microscope objective lens configured to focus the generation beam to a substantially diffraction-limited spot, and wherein the second focusing assembly comprises a second microscope objective lens.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, wherein the second focusing assembly comprises an assembly of lenses and mirrors configured to receive the backscattered light.

### Claim 7 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, wherein the ultrafast pulse laser system comprises:
a common laser configured to emit the probe beam and the generation beam; or
a first laser configured to emit the probe beam and a second laser configured to emit the generation beam.

### Claim 8

(canceled)

### Claim 9 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, further comprising:
a polarization beam splitter (PBS) configured to pass the probe beam and the backscattered light; and
a quarter wave (QW) plate coupled to the PBS configured to pass the probe beam and the backscattered light.

### Claim 10 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, further comprising an amplifier configured to amplify the signals.

### Claim 11 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, wherein the scanning stage is an XY scanning stage configured to perform nanometer step size raster scanning.

### Claim 12 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, wherein the ultrafast pulse laser system comprises a beam splitter configured to:
emit a laser beam; and
split the laser beam into the generation beam and the probe beam.

### Claim 13 (depends on 1)

The nanoscale photoacoustic tomography system of claim 1, further comprising a time delay adjustment mechanism configured to introduce or modify a time delay between the generation beam and the probe beam.

### Claim 14

A method of nanoscale photoacoustic tomography comprising:
emitting, using an ultrafast pulse laser system, a generation beam for generating photoacoustic waves in a biological sample and a probe beam for assessing changes in light reflectivity in the biological sample;
illuminating the biological sample with the generation beam to form the photoacoustic waves in the biological sample, wherein the photoacoustic waves cause changes in the light reflectivity of the biological sample;
illuminating the biological sample with the probe beam at a predetermined delayed time after illuminating the biological sample with the generation beam;
detecting, via an optical detector, backscattered light reflected from the biological sample after illumination with the probe beam; and
recording and processing signals from the optical detector to form an image of at least a portion of the biological sample.

### Claim 15 (depends on 14)

The method of claim 14, wherein the generation beam and/or the probe beam emitted from the ultrafast pulse laser system has a pulse duration in a range of about 100 femtoseconds (fs) to about 100 picoseconds (ps).

### Claim 16

(canceled)

### Claim 17 (depends on 14)

The method of claim 14, further comprising:
using a first focusing assembly to focus the generation beam on a substantially diffraction-limited location on the biological sample; and
using a second focusing assembly to focus the probe beam.

### Claim 18

(canceled)

### Claim 19 (depends on 14)

The method of claim 14, further comprising further emitting the probe beam and the generation beam using a common laser source or using separate laser sources.

### Claim 20

(canceled)

### Claim 21 (depends on 14)

The method of claim 14, further comprising passing the probe beam and the backscattered light through a polarization beam splitter and a quarter wave plate.

### Claim at position 22

-23. (canceled)

### Claim 24 (depends on 14)

The method of claim 14, further comprising splitting a laser beam into the generation beam and the probe beam via a beam splitter.

### Claim 25 (depends on 14)

The method of claim 14, further comprising tuning a wavelength of the generation beam.

### Claim 26 (depends on 14)

The method of claim 14, further comprising introducing or modifying the predetermined delayed time via a time delay adjustment mechanism.

### Claim 27 (depends on 14)

The method of claim 14, further comprising adjusting the predetermined delayed time by mechanical scanning of an optical delay line or by optical sampling.

### Claim at position 27

-52. (canceled)

### Claim 53

A nanoscale photoacoustic tomography system comprising:
an ultrafast pulse laser system configured to:
provide a generation beam for generating photoacoustic waves in a biological sample; and
provide a probe beam for assessing changes in light reflectivity in the biological sample caused by the photoacoustic waves;
a scanning stage configured to mount the biological sample for analysis;
an objective lens configured to:
focus the generation beam on the biological sample;
focus the probe beam on the biological sample; and
collect backscattered light reflected from the biological sample; and
an optical detector configured to:
sense the backscattered light; and
emit signals in response to the backscattered light.

### Claim 54 (depends on 53)

The nanoscale photoacoustic tomography system of claim 53, further comprising a polarization beam splitter (PBS) and a quarter wave (QW) plate coupled to the objective lens and configured to separate the probe beam and the backscattered light.

### Claim at position 30

-56. (canceled)