Bioreactor Volume Control via Automated Feeding and Sampling

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Solution Overview

Problem

Small volume bioreactors face challenges in maintaining a constant working volume during biochemical reactions, which can lead to fluctuations in process conditions such as gas transfer rate and mixing rate, affecting cell growth and productivity.

Innovation Solution

Employing feeding and sampling strategies that maintain the liquid volume within a bioreactor at a substantially constant level, with adjustments to add or remove liquid to keep the volume within a narrow range, and controlling osmolarity between 200 to 600 osmoles/kg to support eukaryotic cell growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If feeding and sampling operations are performed in small volume bioreactors, then nutrient supply and product removal are improved, but volume fluctuations occur that affect process stability

Engineering Contradiction:

Improvecell growth and productivityVSAvoidworking volume stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The system continuously monitors the liquid volume in the bioreactor and automatically adjusts feeding and sampling rates to maintain a target working volume. This closed-loop feedback control ensures that volume fluctuations are minimized while still allowing nutrient supply and product removal operations to proceed, thereby resolving the contradiction between productivity and volume stability.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The system dynamically changes operational parameters (feeding rate, sampling rate) based on the current working volume to maintain stability. When volume deviates from the target, the system adjusts these parameters to bring the volume back to the desired range, allowing continuous productivity improvement without compromising volume stability.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If liquid volume is frequently adjusted to maintain constant working volume, then process control is improved, but system complexity increases

Engineering Contradiction:

Improveprocess condition controlVSAvoidfeeding and sampling system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The system uses a single integrated control mechanism that simultaneously manages both feeding and sampling operations to maintain working volume. This multi-functional approach reduces the need for separate complex control systems for each operation, achieving reliable process control while minimizing overall system complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Volume of stationary object

If small volume bioreactors are used, then space efficiency and resource consumption are improved, but volume control precision becomes more difficult to maintain

Engineering Contradiction:

Improvebioreactor sizeVSAvoidvolume control precision

Core Design Contradiction:

Volume of stationary objectVSManufacturing precision

Solution Approach 1:

The system replaces manual or mechanical volume control methods with automated electronic control and sensing. This substitution enables precise volume monitoring and adjustment in small bioreactors, overcoming the difficulty of maintaining volume control precision in compact systems while preserving the space efficiency benefits of small reactor size.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS11827871B2Small volume bioreactors with substantially constant working volumes and associated systems and methods

Publication Date: 2023.11.28 SANOFI SA(FR)

AI summary

Control of volume in bioreactors and associated systems is generally described. Feeding and/or sampling strategies can be employed, in some embodiments, such that the working volume within the bioreactor remains substantially constant.