Bioreactor Recirculation Circuit for Cell Separation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing cell separation systems for precoat filtration are cumbersome, expensive, and pose environmental contamination risks due to the need for a bioreactor outside the recirculation circuit and the requirement of a second pump for filtration, which complicates handling and increases costs.

Innovation Solution

Integrating the bioreactor with a stirrer into the recirculation circuit and using a powder bag as both a transport and mixing vessel, eliminating the need for a second pump by using a peristaltic pump and designing disposable components to minimize contamination and handling risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the bioreactor is placed outside the recirculation circuit, then the entire cell solution must be held in the powder bag, but this increases handling difficulty and cost

Engineering Contradiction:
Improvefiltration reliabilityVSAvoidhandling ease
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The bioreactor is integrated directly into the recirculation circuit, merging the reaction vessel with the filtration loop. This allows the cell solution to circulate continuously between the bioreactor and powder bag without requiring the powder bag to hold the entire volume, significantly improving handling ease while maintaining filtration reliability

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The recirculation circuit serves multiple functions: it acts as both the bioreactor containment system and the filtration delivery system. The same circuit that maintains cell culture also delivers the filtered product, eliminating the need for separate holding vessels and reducing handling complexity

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

2Productivity

If a second pump is required upstream of the filter, then filtration can be performed, but this increases system complexity and cost

Engineering Contradiction:
Improvefiltration capabilityVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The single peristaltic pump in the recirculation circuit performs dual functions: it circulates the cell solution through the bioreactor and delivers the filtered product through the filter. This multi-functionality eliminates the need for a second pump, reducing system complexity while maintaining full filtration capability

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

Solution Approach 2:

The recirculation circuit enables continuous circulation of the cell solution, allowing filtration to occur continuously as the solution passes through the filter multiple times. This continuous action maintains productivity without requiring additional pumping equipment

Inventive Principle:
Principle #20Continuity of useful action

3Productivity

If larger quantities of filter aid are used, then filtration capacity increases, but handling and storage become more difficult

Engineering Contradiction:
Improvefiltration capacityVSAvoidhandling ease
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The filter aid is divided into manageable portions within the recirculation circuit. Instead of handling large quantities at once, the system processes smaller amounts of filter aid that circulate with the cell solution, making handling and storage easier while maintaining adequate filtration capacity through continuous recirculation

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses the hydraulic action of the recirculating cell solution to transport and distribute the filter aid throughout the circuit. The fluid flow itself serves as the transport mechanism, eliminating the need for separate handling equipment for the filter aid

Inventive Principle:
Principle #29Pneumatics and hydraulics

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

This configuration reduces cell damage, minimizes environmental contamination, and lowers costs by allowing for safer, more efficient cell separation with easier handling and reduced equipment needs, using smaller, manageable quantities of filter aid and enabling variable filter aid amounts as needed.

Implementation Method 1

a peristaltic pump

Methodology Applied
Scientific EffectPeristalsis: Peristalsis

Implementation Method 2

the bioreactor (2), which has a stirrer (8)

Methodology Applied
Scientific EffectStirring: Stirring

Implementation Method 3

a filter (4)

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP2785824B1System and method for cell separation
Publication Date: 2020.12.16 SARTORIUS STEDIM BIOTECH GMBH
  • EP2785824B1 patent drawingFigure 1
  • EP2785824B1 patent drawingFigure 2
  • EP2785824B1 patent drawingFigure 3

AI summary

The invention relates to a system and a method for cell separation via a filter, having a powder bag that can be arranged in a recirculation circuit, is partly filled with a powdery filtering aid and to which a cell solution containing the cells to be separated can be fed from a bioreactor via a pump arranged in the recirculation circuit, wherein the bioreactor, which has a stirrer, is arranged in the recirculation circuit and wherein, when the recirculation circuit is interrupted, the bioreactor can be connected to the filter.