# US 12,031,908 B2 · Fabry Perot interferometry for measuring cell viability

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- Number: US 12,031,908 B2
- Document ID: US12031908B2
- Status: Granted
- Kind: B2
- Application number: 17/094,901
- Filed: 2020-11-11
- Published: 2021-05-13
- Granted: 2024-07-09
- Earliest claimed: 2019-11-11
- Assignees: Nirrin Technologies, Inc.
- Applicants: Nirrin Technologies, Inc.
- Inventors: Bryan A. Hassell; Walid A. Atia; David P. Marchessault
- Web page: https://patentgrep.com/patent/US12031908B2

## CPC

- G01N 21/31: Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry {(G01N21/72 takes precedence)}
- G01N 21/39: using tunable lasers
- C12M 41/32: {of substances in solution}
- G01J 3/26: using multiple reflection, e.g. Fabry-Perot interferometer, variable interference filters
- G01N 21/3577: for analysing liquids, e.g. polluted water
- G01N 21/359: using near infrared light
- G01N 21/45: using interferometric methods; using Schlieren methods
- G01N 33/6854: {Immunoglobulins}
- G01N 21/8507: {Probe photometers, i.e. with optical measuring part dipped into fluid sample}
- G01N 2021/399: {Diode laser}
- G01N 2021/451: {for determining the optical absorption}
- G01N 2201/06113: Coherent sources; lasers
- 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)
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- 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)

## Abstract

A method for studying cell viability and protein aggregation involves establishing a Fabry Perot etalon signal within an optical spectroscopic feature, e.g., in the near infrared region. Protein aggregation and cell viability can be reflected by changes observed in the magnitude of the Fourier Transform peaks observed in the frequency or space domain associated with the contrast of the etalon. In short, the presence of viable cells and protein aggregates can degrade the etalon contrast of an etalon window. In some cases, the concentration of cells and monomeric protein can be measured as well.

## Claims

### Claim 1

A method for analyzing for structures in a solution, the method comprising:
directing light from a light source through the solution, illuminating the solution across a spectral band;
with a detector, detecting the light from the light source after interaction with the solution and, where the detecting of the light occurs after it interacts with an etalon, separate from the solution; and
analyzing a response of the detector to resolve contrast information of the etalon to assess the structures in the solution.

### Claim 2 (depends on 1)

The method of claim 1, wherein the structures are cells or proteins.

### Claim 3 (depends on 1)

The method of claim 1, further comprising splitting the light from the light source to additionally perform absorption spectroscopic analysis of the solution.

### Claim 4 (depends on 1)

The method of claim 1, wherein the solution is a flowing solution.

### Claim 5 (depends on 1)

The method of claim 1, wherein the solution is in a bioreactor.

### Claim 6 (depends on 1)

The method of claim 1, wherein the etalon is established at a volumetric sample detection region of an in-situ probe in a bioreactor.

### Claim 7 (depends on 1)

The method of claim 1, wherein the structures form aggregates.

### Claim 8 (depends on 1)

The method of claim 1, wherein detecting light from the light source after interaction with the solution and an etalon is conducted in a transmission arrangement.

### Claim 9 (depends on 1)

The method of claim 1, wherein detecting light from the light source after interaction with the solution and an etalon is conducted a transflection arrangement.

### Claim 10 (depends on 1)

The method of claim 1, further comprising directing the light from the light source to a second etalon before the interaction with the solution.

### Claim 11 (depends on 1)

The method of claim 1, wherein the light from the light source is directed first to and trough the solution, then to the etalon.

### Claim 12 (depends on 1)

The method of claim 1, wherein the light source is a tunable laser.

### Claim 13 (depends on 12)

The method of claim 12, wherein the tunable laser has a linewidth of less than 1 nanometer (nm).

### Claim 14 (depends on 12)

The method of claim 12, wherein the tunable laser has a linewidth of less than 0.1 nanometers.

### Claim 15 (depends on 1)

The method of claim 1, wherein analyzing the response of the detector includes Fast Fourier Transform processing.

### Claim 16 (depends on 15)

The method of claim 15, wherein analyzing the response of the detector further includes converting from a frequency domain to a space domain.

### Claim 17 (depends on 1)

The method of claim 1, further comprising obtaining an absorption spectrum of the structures.

### Claim 18 (depends on 1)

The method of claim 1, further comprising monitoring changes in contrast information over time.

### Claim 19 (depends on 2)

The method of claim 2, wherein the structures are viable cells.