Bleed Recovery System for Perfusion Bioreactor Product Capture

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Solution Overview

Problem

Bioreactor systems currently discard the bleed stream without recovering the product of interest, leading to significant loss of valuable cellular products, and existing methods to reduce bleed flow rates often have unwanted side effects on culture duration and product quality.

Innovation Solution

A system and method for harvesting product of interest from the bleed of a perfusion bioreactor, which includes a bioreactor, cell retention devices, and a bleed recovery system that separates and collects the product of interest from the bleed material using pumps and vessels, allowing for semi-continuous or continuous collection and processing of the product.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the bleed stream is discarded to maintain target cell density in perfusion bioreactor, then cell density control is achieved, but product of interest is lost

Engineering Contradiction:
Improvecell density controlVSAvoidproduct of interest
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent extracts the product of interest from the bleed stream using a separate recovery system. The bleed stream is diverted to a recovery system that contains the product while allowing the bleed to continue serving its cell density control function, thus resolving the contradiction between maintaining cell density and preventing product loss

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent implements a system where the bleed stream is not simply discarded but rather recovered for its valuable product content. The recovery system captures the product from the bleed stream, transforming the waste disposal process into a resource recovery process that eliminates product loss while maintaining cell density control

Inventive Principle:
Principle #34Discarding and recovering

2Loss of substance

If external environmental levers are adjusted to reduce bleed flow rates, then product loss is reduced, but culture duration and product quality are adversely affected

Engineering Contradiction:
Improveproduct lossVSAvoidproduct quality
Core Design Contradiction:
Loss of substanceVSReliability

Solution Approach 1:

The patent segments the bleed stream processing into two independent pathways: one for cell density control (original bleed function) and one for product recovery (new recovery function). This segmentation allows the system to recover product without altering environmental conditions, avoiding the trade-off between reducing product loss and maintaining product quality

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a recovery system as an intermediary between the bleed stream and waste disposal. This intermediary system recovers the product from the bleed stream without requiring changes to the bioreactor's environmental conditions, thus preventing both product loss and quality degradation

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

Enables the recovery of valuable products from the bleed stream, reducing waste and maintaining target cell density without altering the culture environment, thereby increasing yield and productivity.

Implementation Method 1

a first cell retention device coupled to the bioreactor via tubing, the first cell retention device arranged and configured to separate the product of interest from the medium

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 2

a first harvest pump coupled to the first cell retention device via tubing to transfer the product of interest from the first cell retention device to a first harvest tank

Methodology Applied
Scientific EffectPumping: Pump

Data Source

PatentUS20230383241A1Recovery of perfusion bleed product via alternating tangential flow filtration in a sedimentation reactor
Publication Date: 2023.11.30 REPLIGEN CORP
  • US20230383241A1 patent drawing
  • US20230383241A1 patent drawing

AI summary

A bleed recovery system for use in a bioreactor system is disclosed. The bleed recovery system being configured to recover product of interest from the bleed material of the bioreactor system. In one embodiment, the bioreactor system includes a bleed recovery system for removing cell cultures from the bioreactor. The bleed recovery system includes a bleed pump coupled to the bioreactor so that cell bleed material can be removed from the bioreactor, a bleed vessel for receiving the cell bleed material, a cell retention device coupled to the bleed vessel, a harvest pump coupled to the cell retention device to deposit the product of interest into a second harvest tank, and a bleed pump connected to the bleed vessel to deposit the spent bleed material into a waste tank. Thus arranged, some or all of the product of interest can be separated from the spent medium.