# US 12,222,279 B2 · Flow cell device and bioreactor product monitoring system and method

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- Number: US 12,222,279 B2
- Document ID: US12222279B2
- Status: Granted
- Kind: B2
- Application number: 16/751,895
- Filed: 2020-01-24
- Published: 2020-07-30
- Granted: 2025-02-11
- Earliest claimed: 2019-01-24
- Assignees: Nirrin Technologies, Inc.
- Applicants: Nirrin Technologies, Inc.
- Inventors: Bryan A. Hassell; Aaron Delahanty
- Web page: https://patentgrep.com/patent/US12222279B2

## CPC

- G01N 21/0332: {with temperature control (control of temperature G05D23/00; cryostats F17C3/08)}
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- C12M 47/20: {Heating or cooling (heating or cooling apparatus for laboratory uses B01L7/00)}
- G01N 21/05: Flow-through cuvettes (G01N21/09 takes precedence; handling fluid samples G01N1/10)
- G01N 21/3577: for analysing liquids, e.g. polluted water
- G01N 21/359: using near infrared light
- B01L 2200/0689: Sealing
- B01L 2300/0663: Whole sensors
- B01L 2300/12: Specific details about materials
- B01L 2300/1822: using Peltier elements
- B01L 2400/082: Active control of flow resistance, e.g. flow controllers
- G01N 2021/0389: {Windows}
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- 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}

## Abstract

A flowcell device, including a flow pathway and an optical subassembly, has a flowcell body that is continuous with a sample being analyzed and a temperature controlled surface. The flowcell body can be disposed between a thermalplate, actively regulated by a thermoelectric cooler, and an insulating member. The flowcell device can be employed in a bioreactor monitoring system.

## Claims

### Claim 1

A flowcell device comprising:
a light source;
a flowcell body defining a flow pathway that includes a central cell;
a thermal plate in thermal contact with the flowcell body;
a Peltier device for controlling a temperature of the flowcell body via the thermal plate; and
an optical subassembly, comprising the central cell and adjacent first and second optical windows and a light source and a detector for determining an absorption spectra of a sample in the central cell via the first and second optical windows,
wherein, in the central cell, the flow pathway and a light pathway from a light source through the central cell are orthogonal to one another, and wherein the flow pathway comprises a U-shaped channel that includes the central cell.

### Claim 2 (depends on 1)

The flowcell device of claim 1, wherein the flow pathway is formed of an input channel, an output channel and a channel comprising the central cell and connecting the input channel and the output channel.

### Claim 3 (depends on 2)

The flowcell device of claim 2, wherein the channel connecting the input channel and the output channel is U shaped, having lateral sides defined by a bulk of the flow cell body and front and back sides defined, respectively, by the first optical window and the second optical window.

### Claim 4 (depends on 1)

The flowcell device of claim 1, wherein the input channel and the output channel are defined by steel tubes.

### Claim 5 (depends on 1)

The flowcell device of claim 1, wherein the central cell contains a sample extracted from a bioreactor.

### Claim 6 (depends on 1)

The flowcell device of claim 1, wherein the optical windows are sealed against the flow cell body by gaskets and caps.

### Claim 7 (depends on 1)

The flowcell device of claim 1, wherein the flow cell body is fabricated from a rigid, thermally conductive material.

### Claim 8 (depends on 1)

The flowcell device of claim 1, wherein one or more parts are autoclavable.

### Claim 9 (depends on 1)

The assembly of claim 1, wherein an active surface of the Peltier device is in thermal communication with the flowcell body.

### Claim 10 (depends on 9)

The assembly of claim 9, wherein a passive surface of the Peltier device is in thermal contact with a heat sink.

### Claim 11

An assembly comprising:
a bioreactor containing cells and a culture media;
an actively temperature-controlled thermal plate;
an optical source;
an optical detector;
a flowcell device having a flow cell body defining a channel that includes a central cell;
a pump and a connector, whereby the sample is flowed from the bioreactor by the pump through the connector to the channel that includes the central cell, whereby the pump, the connector, and the channel that includes the central cell are fluidically connected;
wherein the flowcell body has an optical subassembly, comprising the central cell and adjacent first and second optical windows,
wherein the flowcell body is held between an insulating member and the actively temperature-controlled thermal plate while an absorption spectra of the sample is acquired using the optical source and the optical detector.

### Claim 12 (depends on 11)

The assembly of claim 11, wherein the thermal plate is actively temperature controlled by a thermal controller including a thermoelectric cooler, a passive side of the thermoelectric cooler being in contact with a heat sink.

### Claim 13 (depends on 11)

The assembly of claim 11, further comprising a sensor at the thermal plate.

### Claim 14

An optofluidic system, comprising:
a flowcell device having a flowcell body defining a flow pathway that includes a channel comprising a central cell;
a bioreactor containing cells and a culture media;
a pump and a connector, whereby the sample is flowed from the bioreactor with the pump through the connector to the channel comprising the central cell, whereby the pump, the connector, and the channel comprising the central cell are fluidically connected;
an optical subassembly, comprising the central cell, a first optical window and a second optical window;
a light source for directing light through the first optical window, the central cell and the second optical window;
an optical signal detector;
a thermal plate in contact with the flowcell body and supporting a thermoelectric cooler;
a thermal controller;
a sample flow controller;
a light source controller and/or detector controller; and
a computer configured for controlling the thermal controller, the sample flow controller and the light source and/or detector controller, wherein the computer is configured for instructing the thermal controller to maintain a temperature of the sample in the flow cell device while acquiring an absorption spectra of the sample using the light source and the optical signal detector.

### Claim 15 (depends on 14)

The optofluidic system of claim 14, further comprising a conduit to direct a sample from a bioreactor to the flowcell device and a conduit to direct the sample from the flowcell device to the bioreactor.

### Claim 16 (depends on 14)

The optofluidic system of claim 14, wherein a sample flow and a flowcell temperature are independently controlled.

### Claim 17 (depends on 14)

The optofluidic system of claim 14, wherein the computer is configured to regulate a temperature of a flowcell device via the thermal controller while flowing a sample through the flowcell device via the flow controller to obtain absorption spectra of the sample.

### Claim 18 (depends on 17)

The optofluidic system of claim 17, configured for a standard deviation between a stable scan and a scan immediately preceding that is no greater than a threshold standard deviation value.

### Claim 19 (depends on 17)

The optofluidic system of claim 17, configured for controlling the temperature within a range of from about 15 to about 40 degrees centigrade.

### Claim 20 (depends on 1)

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