Disposable Pumphead and Filter Assembly for Bioreactor Waste Removal

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Solution Overview

Problem

Existing bioreactor systems face challenges with metabolic waste buildup, requiring large and expensive setups or time-consuming filtering processes, and existing pump and filter systems often contaminate the sterile environment during maintenance.

Innovation Solution

A disposable pumphead and tangential flow filter system that separates metabolic wastes from cells using a low-shear, gamma-stable pump and hollow fiber filter, allowing for quick and sterile operation with minimal cell damage, and eliminating the need for autoclaving.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If a large and expensive bioreactor is used to handle metabolic waste buildup, then cell growth capacity is improved, but system cost and size increase

Engineering Contradiction:
Improvecell growth capacityVSAvoidbioreactor size
Core Design Contradiction:
ProductivityVSVolume of stationary object

Solution Approach 1:

The system divides the bioreactor into functional segments: a smaller main bioreactor for cell growth and a separate filtration system for metabolic waste removal. This segmentation allows the bioreactor to be smaller while maintaining high cell growth capacity through continuous waste removal via the filtration module.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A filtration system acts as an intermediary between the bioreactor and the environment, continuously removing metabolic wastes. This intermediary function enables the bioreactor to maintain high cell density without requiring large size, as the filter handles waste removal that would otherwise limit growth capacity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If filtering biological material is performed to continue biological activity, then cell growth is maintained, but time is lost due to filtering operations

Engineering Contradiction:
Improvebiological activity continuityVSAvoidfiltering operation time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The filtration system operates continuously alongside cell growth, rather than as a periodic batch operation. The pump circulates bioreactor fluid through the filter continuously, removing metabolic wastes in real-time, which maintains biological activity without interrupting the growth process for filtering operations.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system performs preliminary waste removal through continuous filtration before metabolic wastes can accumulate to limiting concentrations. This preliminary action prevents growth inhibition rather than correcting it after the fact, maintaining continuous biological activity without time loss.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If pump and filter systems are used for filtering, then metabolic waste removal is achieved, but sterility is compromised during maintenance

Engineering Contradiction:
Improvemetabolic waste removalVSAvoidsterile environment
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The pump and filter components are designed as disposable, single-use items that are pre-sterilized. After one use, the entire assembly is discarded rather than serviced, eliminating the risk of sterility compromise during maintenance while continuing to provide effective metabolic waste removal.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The disposable pump and filter are pre-sterilized before use, performing the sterilization action in advance. This preliminary sterilization ensures sterility is maintained throughout the operation without requiring subsequent maintenance that could compromise the sterile environment.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If mechanical pump components are used, then fluid circulation is achieved, but debris is introduced into the bioreactor

Engineering Contradiction:
Improvefluid circulationVSAvoiddebris contamination
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The system replaces traditional mechanical pump components with a magnetic drive mechanism. The pump uses magnetic fields to drive fluid circulation without mechanical seals or moving parts that contact the fluid, eliminating the source of debris contamination while maintaining effective circulation.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

A magnetic field acts as an intermediary to transfer energy to the pump impeller without mechanical contact. The magnetic drive transmits rotational force through the pump housing walls, eliminating mechanical seals and bearings that would otherwise generate debris into the bioreactor fluid.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 solution enables efficient cell production with reduced bioreactor size, maintaining sterility during operation, and simplifying maintenance by providing a pre-sterilized, scalable system that connects to various reactor types without impacting viability.

Implementation Method 1

The filter system cycles Bioreactor fluid through a hollow fiber tangential flow filter which separates metabolic wastes (as well as proteins) from cells produced in Bioreactor

Methodology Applied
Scientific EffectTangential flow filtration: Filter (physical)

Implementation Method 2

The pump is a low shear gamma stable pump gently cycling bioreactor fluid through the filter with minimal damage to the cells produced in the bioreactor. The pumphead and hollow fiber tangential flow filter are disposable. The pump motor is part of the control system and is reusable.

Methodology Applied
Scientific EffectMagnetic coupling: Magnetic Field

Data Source

PatentUS11555174B2Method for proliferation of cells within a bioreactor using a disposable pumphead and filter assembly
Publication Date: 2023.01.17 REPLIGEN CORP
  • US11555174B2 patent drawing
  • US11555174B2 patent drawing
  • US11555174B2 patent drawing

AI summary

A method for promoting biological activity uses a filter system to increase cell production of a fed batch bioreactor. The filter system cycles bioreactor fluid through a hollow fiber tangential flow filter which separates metabolic wastes (as well as proteins) from cells produced in bioreactor and returned to fed batch bioreactor, improving cell production in the fed batch bioreactor. The filter system includes a disposable pump and filter, and a reusable control system. The pump is a low shear gamma stable pump gently cycling bioreactor fluid through the filter with minimal damage to the cells produced in the bioreactor. The pumphead and hollow fiber tangential flow filter are disposable. The pump motor is part of the control system and is reusable. The pumphead and filter are provided as an assembled and pre-sterilized unit allowing simple and quick attachment to the fed batch bioreactor, and simple and quick disposal.