In-situ Sensor Integration in Single-Use Bioreactor Head Plates

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Solution Overview

Problem

Commercially available single-use small volume bioreactors lack the capability for in-situ monitoring of metabolites like glucose, requiring off-line sampling which increases handling efforts and contamination risks, and limits the ability to monitor glucose levels in real-time.

Innovation Solution

Incorporating one or more in-situ sensors, such as an electrochemical and/or enzyme-based glucose sensor, directly in contact with the cultivation medium, allowing for continuous glucose monitoring and reducing the need for off-line sampling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If off-line sampling is used to monitor glucose levels, then the bioreactor can be operated with simple sensor configuration, but handling efforts increase and contamination risk increases

Engineering Contradiction:
Improvecontamination riskVSAvoidhandling efforts
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The reactor head plate is designed as a multi-functional component that integrates multiple sensor ports and sampling ports into a single structure. This allows the bioreactor to perform both cultivation and multi-parameter monitoring functions through one unified component, reducing the need for separate sampling operations and minimizing contamination risks while maintaining ease of operation.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If multiple in-situ sensors are added to monitor metabolites, then real-time monitoring capability is improved, but device complexity increases

Engineering Contradiction:
Improvereal-time monitoring capabilityVSAvoidsensor configuration complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Multiple sensor ports and sampling ports are merged into a single integrated reactor head plate structure. This consolidation allows multiple sensors (pH, dissolved oxygen, glucose, lactate) to be mounted on one component rather than requiring separate mounting structures, thereby reducing overall device complexity while enabling comprehensive real-time monitoring of multiple metabolites.

Inventive Principle:
Principle #5Merging (Combining)

3Loss of time

If in-situ glucose sensor is implemented, then analytical timelines are shortened, but sensor integration complexity increases

Engineering Contradiction:
Improveanalytical timelinesVSAvoidsensor integration complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The reactor head plate is pre-designed with dedicated sensor ports and mounting structures during the manufacturing stage. This preliminary preparation of the mounting infrastructure eliminates the need for complex integration work when installing glucose sensors, allowing rapid sensor deployment and reducing analytical timelines without significantly increasing operational complexity.

Inventive Principle:
Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables real-time glucose monitoring, reducing contamination risks, lowering cell density and product yield issues, and allowing for earlier corrective measures, while maintaining transferability to large-scale processes.

Implementation Method 1

the glucose sensor is an electrochemical and/or enzyme-based sensor

Methodology Applied
Scientific EffectElectrochemical reaction: Electrochemiluminescence

Implementation Method 2

the pH sensor is a pH electrode

Methodology Applied
Scientific EffectIon conduction: Conduction (electrical)

Data Source

PatentEP4085126B1Single-use cell culture container with two or more in-situ online sensors
Publication Date: 2024.07.03 F HOFFMANN LA ROCHE & CO AG
  • EP4085126B1 patent drawingFigure 1
  • EP4085126B1 patent drawingFigure 2
  • EP4085126B1 patent drawingFigure 3

AI summary

Herein is reported a small volume bioreactor comprising a cultivation vessel and a reactor head plate, wherein the cultivation vessel has a working volume of from 20 ml to 350 ml and comprises two or more in-situ sensors, wherein the reactor head plate comprises an in-situ sensor port, wherein to the in-situ sensor port at least one in-situ glucose sensor and one in-situ pH sensor are connected.