# US 10,309,902 B2 · Characterization of trace crystallinity by second harmonic generation microscopy

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,309,902 B2
- Document ID: US10309902B2
- Status: Granted
- Kind: B2
- Application number: 15/514,893
- Filed: 2015-09-28
- Published: 2017-07-27
- Granted: 2019-06-04
- Earliest claimed: 2014-09-28
- Assignees: Purdue Research Foundation
- Applicants: Purdue Research Foundation
- Inventors: Garth Jason Simpson; Paul David Schmitt
- Web page: https://patentgrep.com/patent/US10309902B2

## CPC

- G01N 21/65: Raman scattering
- G01N 21/636: {using an arrangement of pump beam and probe beam; using the measurement of optical non-linear properties; (non-linear optics per se G02F1/35)}
- G01N 23/207: Diffractometry using detectors, e.g. using a probe in a central position and one or more displaceable detectors in circumferential positions
- G01N 2223/606: texture
- G01N 2223/612: biological material
- 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

A method for quantifying crystallinity within a sample using second harmonic generation microscopy is described herein. In one aspect, a method for reducing the timeframe for accelerated stability testing of amorphous solid dispersions of active pharmaceutical ingredients though identifying regions of interest to quantify crystallinity and composition is presented herein.

## Claims

### Claim 1

A method for identifying composition, the method comprising:
acquiring at least one second harmonic generation (SHG) image of a sample;
analyzing the at least one SHG image to obtain at least one field of view;
generating a plurality of particle histograms from the at least one field of view;
locating at least one region of interest within the at least one field of view of the at least one SHG image;
acquiring at least one Raman spectrum from the at least one region of interest;
assessing composition of an individual particle via spectral analysis of the at least one Raman spectrum;
acquiring at least one x-ray diffraction (XRD) image from the at least one region of interest;
producing a representative powder pattern of the individual particle from the at least one XRD image;
and
comparing the representative powder pattern with a set of powder patterns from a database to validate composition of the individual particle.

### Claim 2 (depends on 1)

The method of claim 1, wherein the representative power pattern is produced using mean-subtracted autocorrelation of the XRD image along an azimuthal axis.

### Claim 3 (depends on 1)

The method of claim 1, further comprising collecting SHG light in the transmission direction.

### Claim 4

A method for identifying composition of an individual particle, the method comprising:
acquiring at least one second harmonic generation (SHG) image of a sample;
analyzing the at least one SHG image to obtain at least one field of view;
generating a plurality of particle histograms from the at least one field of view;
locating at least one region of interest within the at least one field of view of the at least one SHG image;
acquiring at least one Raman spectrum from the at least one region of interest;
assessing composition of the individual particle via spectral analysis of the at least one Raman spectrum; and
determining composition of the individual particle.

### Claim 5 (depends on 4)

The method of claim 4, wherein the determining composition of the individual particle comprises: comparing a Raman spectrum of the individual particle with a reference spectrum from a database to validate composition of the individual particle.

### Claim 6

A method for identifying composition of an individual particle, the method comprising:
acquiring at least one second harmonic generation (SHG) image of a sample;
analyzing the at least one SHG image to obtain at least one field of view;
generating a plurality of particle histograms from the at least one field of view;
locating at least one region of interest within the at least one field of view of the at least one SHG image;
acquiring at least one x-ray diffraction (XRD) image from the at least one region of interest;
assessing composition of the individual particle via spectral analysis of the at least one XRD image; and
determining composition of the individual particle.

### Claim 7 (depends on 6)

The method of claim 6, wherein the determining composition of the individual particle comprises: comparing an X-ray spectrum of the individual particle with a reference spectrum from a database to validate composition of the individual particle.

### Claim 8 (depends on 7)

The method of claim 7, wherein the x-ray spectrum of the individual particle is produced using mean-subtracted autocorrelation of the XRD image along an azimuthal axis.