# US 9,554,743 B2 · Methods for optical identification and characterization of abnormal tissue and cells

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- Number: US 9,554,743 B2
- Document ID: US9554743B2
- Status: Granted
- Kind: B2
- Application number: 12/650,437
- Filed: 2009-12-30
- Published: 2010-04-29
- Granted: 2017-01-31
- Earliest claimed: 2007-02-01
- Assignees: LS Biopath, Inc.
- Applicants: Moshe Sarfaty; Amir Lev
- Inventors: Moshe Sarfaty; Amir Lev
- Web page: https://patentgrep.com/patent/US9554743B2

## CPC

- A61B 5/415: {the glands, e.g. tonsils, adenoids or thymus}
- A61B 5/0075: {by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy (A61B5/0071 takes precedence)}
- A61B 5/0084: {for introduction into the body, e.g. by catheters (A61B5/1459 takes precedence)}
- A61B 5/418: {lymph vessels, ducts or nodes}
- G01J 3/0218: {using optical fibers}
- G01J 3/0291: {Housings; Spectrometer accessories; Spatial arrangement of elements, e.g. folded path arrangements}
- G01J 3/44: Raman spectrometry; Scattering spectrometry {; Fluorescence spectrometry}
- G01N 21/658: {enhancement Raman, e.g. surface plasmons}
- A61B 5/0091: {for mammography}
- A61B 2562/0233: Special features of optical sensors or probes classified in A61B5/00
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N)
- 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)

## Abstract

An optical system and apparatus for the diagnosis of a biological sample is disclosed. An embodiment of the apparatus includes an optical probe, a probe head distally connectable to the optical probe, the optical probe further comprising at least one optical element for applying an electromagnetic radiation of a first wavelength to the biological sample, and one or more collection elements positioned proximate the at least one optical element; and an analyzer for analyzing a signal received from the biological sample by the one or more collection elements.

## Claims

### Claim 1

A method of diagnosing cancer in a biological tissue of a patient in real-time comprising:
contacting the biological tissue with an optical probe having a probe tip distally connectable to the optical probe, the probe tip further comprising:
at least one application element comprising a decladded optical fiber element partially coated with metallic nanosized conductive beads on an outer surface of the decladded optical fiber element, for applying electromagnetic radiation of a first optical wavelength directly to the biological tissue, one or more separate collection elements each of the one or more separate collection elements comprising a plurality of cladded optical fibers positioned around the decladded optical fiber covered with metallic nanosized beads and having an end terminating proximate the distal end of the decladded optical fiber element, a fiber bundle array connector connected to the decladded optical fiber element at a proximal end and the one or more separate collection elements at a distal end, and further wherein the collection elements collect a near-field Surface Enhanced Raman Spectroscopy (SERS) response signal from the biological tissue in response to the applied electromagnetic radiation, reflected from the biological tissue, and a computer configured to analyze a spectrum of the response signal received from the biological tissue by the one or more separate collection elements;
emitting electromagnetic radiation of a first wavelength along a length of the decladded optical fiber element in a direction perpendicular to the longitudinal axis of the decladded optical fiber;
collecting the near-field Surface Enhanced Raman Spectroscopy response signal from the biological tissue through the collection elements;
analyzing, with the computer, the collected near-field Surface Enhanced Raman Spectroscopy response signal received from the biological tissue to produce a real-time result to identify one or more molecular signatures of the biological tissue;
calculate, with the computer, the normal distribution of the molecular signatures of the biological tissue; and
determine, with the computer, a diagnosis of cancer of the biological tissue by comparing the normal distribution of the biological tissue with a benign reference tissue normal distribution.

### Claim 2 (depends on 1)

The method of claim 1, wherein the step of contacting the biological tissue further comprises applying the optical probe to a tissue site within a body of a mammal.

### Claim 3 (depends on 1)

The method of claim 1, wherein the step of contacting the biological tissue further comprises inserting the optical probe into a body of a mammal through an endoscope.

### Claim 4 (depends on 1)

The method of claim 1 further comprising the step of identifying suspect areas of tissue with the computer for identifying and characterizing abnormal tissue and cells prior to contacting the biological tissue with the optical probe.

### Claim 5 (depends on 1)

The method of claim 1, further comprising the step of replacing the probe head with a second probe tip and thereafter emitting electromagnetic radiation of a second wavelength, collecting the response signal from the biological tissue, analyzing the signal received from the biological tissue to produce a result, and diagnosing the biological tissue based on the result.

### Claim 6 (depends on 5)

The method of claim 5, the electromagnetic radiation of the first wavelength and the electromagnetic radiation of the second wavelength comprise the same wavelength.

### Claim 7 (depends on 1)

The method of claim 1, wherein the benign reference tissue is obtained from the same patient.

### Claim 8 (depends on 1)

The method of claim 1, wherein the collection elements comprise a second set of electrodes different from the application element and the step of applying electromagnetic radiation of the first wavelength to the biological tissue of the patient, further comprises the step of sending a signal to the application element.

### Claim 9 (depends on 8)

The method of claim 8, wherein the step of collecting the response signal from the biological tissue further comprises the step of collecting the signal utilizing the second set of electrodes.
