# US 12,180,445 B2 · Device for monitoring a biological process in a liquid medium

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- Number: US 12,180,445 B2
- Document ID: US12180445B2
- Status: Granted
- Kind: B2
- Application number: 17/151,158
- Filed: 2021-01-16
- Published: 2021-05-20
- Granted: 2024-12-31
- Earliest claimed: 2018-07-18
- Assignees: Hamilton Bonaduz AG
- Applicants: Hamilton Bonaduz AG
- Inventors: Dirk Schoenfuss; Frederic Juillerat
- Web page: https://patentgrep.com/patent/US12180445B2

## CPC

- C12M 23/14: {Bags}
- C12M 23/20: {Material Coatings (immunocoatings C12M25/00)}
- C12M 23/26: {flexible (flexible containers for laboratory use B01L3/505)}
- C12M 23/28: {disposable or single use}
- C12M 29/18: {External loop; Means for reintroduction of fermented biomass or liquid percolate (loop type reactors for chemical or physical processes B01J19/2435)}
- 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 device for monitoring a biological process in a liquid medium includes a wall portion, a silanization layer and a sensor arrangement. The device attaches to a container of a bioreactor and can be used with disposable bioreactors. The wall portion is adapted to retain the liquid medium during operation of the bioreactor. A through-hole is disposed in the wall portion. A silanization layer covers the surface encircling the through-hole and the wall portion between the liquid medium and the wall portion. The sensor arrangement includes a glass layer, a substrate and an electrode. The glass layer is bonded by an adhesive to the silanization layer so as to cover the through-hole. The electrode is mounted on the substrate and measures electrical conductivity through the liquid medium. The sensor arrangement also includes an optical sensor that detects electromagnetic radiation that passes from the liquid medium through the glass layer.

## Claims

### Claim 1

A device for monitoring a biological process in a liquid medium, comprising:
a wall portion that is adapted to retain the liquid medium during operation of the device, wherein a through-hole is disposed in the wall portion;
a silanization layer disposed on the wall portion between the liquid medium and the wall portion;
a sensor arrangement that includes a glass layer; and
an adhesive that bonds the glass layer to the silanization layer such that the glass layer covers the through-hole.

### Claim 2 (depends on 1)

The device of claim 1, wherein the wall portion has a through-hole surface encircling the through-hole, wherein the silanization layer covers the through-hole surface, and wherein the sensor arrangement is disposed adjacent to the through-hole.

### Claim 3 (depends on 2)

The device of claim 2, wherein the through-hole surface that is covered by the silanization layer is oriented substantially perpendicularly to the glass layer.

### Claim 4 (depends on 1)

The device of claim 1, wherein the adhesive is selected from the group consisting of: a silicone adhesive and a two-component epoxy resin adhesive.

### Claim 5 (depends on 1)

The device of claim 1, wherein the wall portion is made of high-density polyethylene (HDPE).

### Claim 6 (depends on 1)

The device of claim 1, wherein the device is attached to a container of a bioreactor, wherein the container is made of a flexible material, and wherein the wall portion is rigid.

### Claim 7 (depends on 1)

The device of claim 1, wherein the sensor arrangement has an optical sensor adapted to detect electromagnetic radiation that passes from the liquid medium through the glass layer.

### Claim 8 (depends on 1)

The device of claim 1, wherein the sensor arrangement also includes a substrate disposed adjacent to the glass layer, and wherein a sensor is mounted to the substrate.

### Claim 9 (depends on 8)

The device of claim 8, wherein the sensor includes an electrode adapted to measure electrical conductivity through the liquid medium.

### Claim 10 (depends on 1)

The device of claim 1, wherein the sensor arrangement includes a substrate disposed adjacent to the glass layer, wherein an electrode is attached to the glass layer, and wherein the glass layer is disposed between the electrode and the substrate.

### Claim 11 (depends on 1)

The device of claim 1, wherein the sensor arrangement includes a substrate disposed adjacent to the glass layer, wherein a first electrode and a second electrode are mounted to the substrate, and wherein a portion of the glass layer is disposed on the substrate between the first electrode and the second electrode.

### Claim 12 (depends on 11)

The device of claim 11, wherein the first and second electrodes have bottoms attached to the substrate, top surfaces opposite the bottoms, and side surfaces between the bottoms and the top surfaces, and wherein the side surfaces of the first and second electrodes are completely covered by the glass layer.

### Claim 13 (depends on 12)

The device of claim 12, wherein only a center region of each of the top surfaces of the first and second electrodes is not covered by the glass layer.

### Claim 14 (depends on 11)

The device of claim 11, wherein the sensor arrangement is adapted to sense electrical conductivity through the liquid medium between the first electrode and the second electrode.

### Claim 15

A bioreactor comprising:
a container adapted to retain a liquid medium in an interior of the bioreactor;
a wall portion of a monitoring device, wherein the wall portion forms part of the container, and wherein a through-hole is disposed in the wall portion; and
a sensor arrangement of the monitoring device, wherein the sensor arrangement includes a substrate, a glass layer and an electrode, wherein the electrode is mounted on the substrate, wherein the substrate is disposed between the electrode and the glass layer, wherein the glass layer is attached to the wall portion such that the glass layer covers the through-hole, and wherein the electrode is disposed in the interior of the bioreactor.

### Claim 16 (depends on 15)

The bioreactor of claim 15, wherein the wall portion has a through-hole surface encircling the through-hole, wherein a silanization layer covers the through-hole surface, and wherein the glass layer is bonded to the silanization layer.

### Claim 17 (depends on 16)

The bioreactor of claim 16, wherein the silanization layer covers the wall portion between the liquid medium and the wall portion.

### Claim 18 (depends on 15)

The bioreactor of claim 15, wherein the container is made of a flexible material, wherein the wall portion is rigid, and wherein the flexible container is attached to the rigid wall portion.

### Claim 19 (depends on 15)

The bioreactor of claim 15, wherein the bioreactor is disposable.

### Claim 20 (depends on 15)

The bioreactor of claim 15, wherein the sensor arrangement includes an optical sensor adapted to detect electromagnetic radiation that passes from the liquid medium through the glass layer.

### Claim 21 (depends on 15)

The bioreactor of claim 15, wherein the electrode is adapted to measure electrical conductivity through the liquid medium.

### Claim 22 (depends on 15)

The bioreactor of claim 15, wherein the glass layer is attached to the wall portion using an adhesive selected from the group consisting of: a silicone adhesive and a two-component epoxy resin adhesive.

### Claim 23 (depends on 15)

The bioreactor of claim 15, wherein the electrode has a bottom that is attached to the substrate, a top surface opposite the bottom, and side surfaces between the bottom and the top surface, and wherein the side surfaces of the electrode are completely covered by glass of a second glass layer.