US-12624326-B2 - Sensor receptacle for using a conventional sensor with a single-use bioreactor while maintaining the sterility of the single-use bioreactor

US12624326B2US 12624326 B2US12624326 B2US 12624326B2US-12624326-B2

Abstract

A bioreactor system ( 1 ) has a pre-sterilized single-use bioreactor ( 2 ) with a reactor wall ( 20 ) surrounding an interior chamber ( 21 ) that receives a fluid medium (M). A sensor ( 3 ) for detecting an analyte in the medium has a sensor housing ( 30 ) with an outside thread ( 31 ) and a sensor shaft ( 32 ), a distal end portion ( 33 ) of which has an end face ( 34 ) with a region ( 35 ) permeable to the analyte. A sensor receptacle ( 4 ) connected to the reactor wall receives the sensor, to maintain the sterility of the single-use bioreactor. A circumferential flange ( 40 ) fixes the sensor receptacle to the reactor wall. The flange has an inside thread ( 42 ) that receives the outside thread. A wall ( 43 ) of the sensor receptacle is connected to the flange, and together with the sensor shaft, protrudes into the interior chamber, separating the sensor from the interior chamber.

Inventors

Anne Maier
Stefan Bardeck

Assignees

METTLER-TOLEDO GMBH

Dates

Publication Date: 20260512
Application Date: 20210408
Priority Date: 20200415

Claims (15)

1 . A sensor receptacle for receiving a sensor for a single-use bioreactor, such that an interior chamber of the single-use bioreactor is separated from the sensor and a sterile state of the single-use bioreactor is maintained, wherein the sensor receptacle further comprises: a circumferential flange designed to be fixed to a reactor wall of the bioreactor, wherein the flange has a fastening region comprising an inside thread provided on a circumferential inner side of the flange and configured to receive an outside thread of a fastening region of a sensor housing of the sensor to produce a detachable, force-fitting and/or form-fitting connection between the flange and the sensor housing, a wall of the sensor receptacle, which wall is connected to the flange and which is set up and provided for separating the sensor from the interior chamber of the single-use bioreactor, wherein the wall is designed in such a way that an end face of a distal end portion of a sensor shaft of the sensor bears against a portion of the wall of the sensor receptacle, when the sensor is arranged in the sensor receptacle and the fastening region of the sensor housing is connected to the fastening region of the flange as intended, wherein at least the portion of the wall of the sensor receptacle is formed from a flexible membrane which is permeable to an analyte to be measured by means of the sensor in such a way that the analyte can pass through the flexible membrane to a region, permeable to the analyte, of the end face of the distal end portion of the sensor shaft.
2 . A bioreactor system, comprising: a pre-sterilized single-use bioreactor having a reactor wall which surrounds an interior chamber of the single-use bioreactor, the interior chamber being designed to receive a fluid medium; a sensor being designed to detect a gaseous analyte present in the medium or an analyte dissolved in the medium, the sensor having a sensor housing with a fastening region and a sensor shaft, the sensor shaft having a distal end portion with an end face which has a region which is permeable to the analyte; the sensor receptacle of claim 1 connected to the reactor wall and designed to receive the sensor, such that the sterility of the single-use bioreactor is maintained, the sensor receptacle having the circumferential flange via which the sensor receptacle is fixed to the reactor wall, the flange having the fastening region configured to engage in a releasable as well as the force-fitting and/or form-fitting connection with the fastening region of the sensor housing and the sensor receptacle having the wall connected to the flange which wall, together with the sensor shaft, protrudes into the interior chamber of the single-use bioreactor and thus separates the sensor from the interior chamber when the sensor is arranged in the sensor receptacle and is connected to the fastening region of the flange of the sensor receptacle by means of its fastening region as intended.
3 . The bioreactor system according to claim 2 , wherein the sensor receptacle is configured in such a way that the portion of the wall is pre-stressed against the end face of the distal end portion of the sensor shaft when the sensor is arranged in the sensor receptacle and the fastening region of the sensor housing is connected to the fastening region of the flange as intended.
4 . The bioreactor system according to claim 3 , characterized in that the wall of the sensor receptacle is designed to be expandable, such that the wall is expanded in a direction in which the sensor shaft can be inserted into the sensor receptacle when the sensor is arranged in the sensor receptacle and the fastening region of the sensor housing is connected to the fastening region of the flange as intended.
5 . The bioreactor system according to claim 4 , wherein the wall is completely formed by the flexible membrane.
6 . The bioreactor system according to claim 2 , wherein the wall of the sensor receptacle has a rigid wall portion, which extends in a circumferential direction and is connected to the portion of the wall, wherein the portion of the wall is formed by the flexible membrane.
7 . The bioreactor system according to claim 6 , wherein the flexible membrane is formed from a material selected from the group consisting of an inorganic polymer, an organic polymer, and a poly(organo)siloxane.
8 . The bioreactor system according to claim 2 , wherein the analyte is one of the following analytes: oxygen, CO 2 , SO 2 , H 2 O 2 , NO x , a halogenated hydrocarbon.
9 . The bioreactor system according to claim 2 , wherein the sensor shaft has a sleeve at the distal end portion of the sensor shaft, on which sleeve the permeable region is fixed, or which is designed for fixing the permeable region to the sensor, wherein the sleeve can be detachably connected to a base of the sensor shaft.
10 . The bioreactor system according to claim 2 , wherein the reactor wall is designed to be rigid or at least partially rigid, or in that the reactor wall is designed to be flexible.
11 . The bioreactor system according to claim 2 , wherein the portion of the wall of the sensor receptacle is formed from a material which does not have a chromophore.
12 . The bioreactor system according to claim 2 , characterized in that the wall of the sensor receptacle is designed to be expandable, such that the wall is expanded in a direction in which the sensor shaft can be inserted into the sensor receptacle when the sensor is arranged in the sensor receptacle and the fastening region of the sensor housing is connected to the fastening region of the flange as intended.
13 . The bioreactor system according to claim 2 , wherein the wall is completely formed by the flexible membrane.
14 . The bioreactor system according to claim 2 , wherein the flexible membrane is formed from a material selected from the group consisting of: an inorganic polymer, an organic polymer, and a poly(organo) siloxane.
15 . A method for measuring an analyte in a medium using the bioreactor system of claim 2 , said method comprising the steps of: providing the pre-sterilized single-use bioreactor, arranging the separate sensor in the sensor receptacle wherein the fastening region of the sensor housing is connected in a force-fitting and/or form-fitting manner to the fastening region of the flange of the sensor receptacle in such a way that the end face of the distal end portion of the sensor shaft bears against the portion of the wall of the sensor receptacle, and measuring a concentration of the analyte of the medium located in the interior chamber by means of the sensor.

Description

The invention relates to a bioreactor system comprising a single-use bioreactor and a sensor for measuring an analyte contained in a medium located in an interior chamber of the single-use bioreactor. Furthermore, the invention relates to a method which is carried out using the bioreactor system and to a sensor receptacle with which a single-use bioreactor can be equipped in such a way that said single-use bioreactor can be used together with a conventional sensor without breaking the sterility of the single-use bioreactor. A single-use bioreactor is a bioreactor that is only used for carrying out a single process and is then disposed of. The use of a new, pre-sterilized single-use bioreactor in each case for each individual process makes it possible to reduce the risk of contamination, wherein, furthermore, the effort of cleaning the bioreactor is eliminated. Single-use bioreactors are also referred to as disposable bioreactors. Single-use bioreactors are becoming increasingly important as process reactors, so it is desirable to be able to equip such a reactor with a sensor so that an analyte contained in a medium located in the single-use bioreactor is measurable. Therefore, it is the object of the invention to provide a bioreactor system which has a single-use bioreactor which permits the use of a sensor for measuring an analyte present in the single-use bioreactor in a simple and efficient manner. This object is achieved by a single-use bioreactor system with the features of claim 1. Advantageous configurations of the single-use bioreactor system are specified in the corresponding dependent claims and are described below. According to claim 1, there is disclosed a bioreactor system, comprising: a pre-sterilized single-use bioreactor having a reactor wall which surrounds an interior chamber of the single-use bioreactor, the interior chamber being designed to receive a fluid medium;a separate sensor being designed to detect a gaseous analyte present in the medium or an analyte dissolved in the medium, the sensor having a sensor housing with a fastening region (e.g., in the form of an outside thread) and a sensor shaft, the sensor shaft having a distal end portion with an end face which has a region which is permeable to the analyte for passing through the analyte, in such a way that in particular the analyte in the sensor housing can be measured by respective measuring unit or sensor system;a sensor receptacle connected fluid-tight to the reactor wall and designed to receive the sensor, such that the sterility of the single-use bioreactor is maintained, the sensor receptacle having a circumferential flange via which the sensor receptacle is fixed to the reactor wall, the flange having a fastening region (e.g., an inside thread at a circumferential inner side of the flange) configured to be connected in a detachable force-fitting and/or form-fitting manner with the fastening region of the sensor housing (e.g., the outside thread of the sensor housing can be screwed into the inside thread of the flange), and the sensor receptacle having a wall connected to the flange which wall, together with the sensor shaft, protrudes into the interior chamber of the single-use bioreactor when the sensor is arranged in the sensor receptacle and is connected to the fastening region of the sensor receptacle or the flange by means of its fastening region as intended, wherein the wall of the sensor receptacle is designed in such a way, that the end face of the distal end portion of the sensor shaft bears against a portion of the wall of the sensor receptacle when the fastening region of the sensor is connected to the fastening region of the flange as intended, wherein at least said portion of the wall of the sensor receptacle is formed from a flexible membrane, which is permeable to the analyte so that the analyte can pass through the flexible membrane to the permeable region of the sensor. Due to the sensor receptacle, the invention advantageously allows the use of an unmodified standard sensor as is used also in multi-use bioreactors made of glass or stainless steel. In this case, the entire sensor as such—in contrast to the single-use bioreactor—is reusable on account of the detachable connection to the sensor receptacle and the arrangement outside the interior chamber of the single-use bioreactor, so that no complicated pre-sterilization or autoclaving of the sensor (completely or in parts) or no storage of the sensor as a whole or in parts together with the single-use bioreactor is required. The present invention is specifically designed for single-use bioreactors (see above). However, according to a further aspect of the invention, it is also conceivable, instead of a single-use bioreactor, to use a bioreactor provided, for example, for a small number of uses (e.g., two to three cycles). If the sensor is correctly arranged in the sensor receptacle, the sensor shaft protrudes with the distal end portion into the interior