Bioprocess Cell Separation Device with Backflush Dilution

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Solution Overview

Problem

Conventional cell separation methods in biopharmaceutical processes face challenges with high cell concentrations and viscosity, leading to reduced filtration performance and economic inefficiencies, particularly in cross-flow filtration using microfiltration membranes, where blockage and viscosity issues limit protein yield and require costly dilution.

Innovation Solution

A device arrangement with a separate backflush line and pump for rinsing liquid, allowing simultaneous membrane cleaning and dilution during filtration, using a buffer solution or substrate, to maintain optimal filtration performance and protein yield, and incorporating sensors for real-time process control.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cross-flow filtration is used to separate cells from culture medium, then cell separation efficiency is improved, but filtration performance drops sharply due to increasing viscosity and blockage

Engineering Contradiction:

Improvecell separation efficiencyVSAvoidfiltration performance

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent implements periodic backflushing cycles where the filtration process is intermittently interrupted to reverse the flow direction through the membrane. This periodic reversal cleans the membrane surface by dislodging accumulated cells and bio-mass, preventing continuous blockage and maintaining stable filtration performance throughout the separation process

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The system performs preliminary dilution of the culture medium with buffer solution or substrate before the viscosity becomes excessively high. This proactive dilution prevents the medium from reaching critical viscosity levels that would cause sharp performance drops, maintaining optimal flow conditions throughout filtration

Inventive Principle:

Principle #10Preliminary action

2Quantity of substance

If filtration is continued to maximize protein yield, then protein recovery increases, but viscosity increases leading to process interruption

Engineering Contradiction:

Improveprotein yieldVSAvoidprocess continuity

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The system incorporates sensors that continuously monitor viscosity and other process parameters during filtration. When viscosity approaches critical levels, the feedback control system automatically triggers backflushing cycles or dilution actions, allowing the process to continue maximizing protein yield without manual intervention or interruption

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent dynamically adjusts process parameters including flow rate, pressure, and composition of the culture medium during filtration. By changing these parameters in response to accumulating bio-mass, the system maintains optimal filtration conditions throughout the process, enabling continuous operation at high protein recovery levels

Inventive Principle:

Principle #35Parameter changes

3Reliability

If dilution with buffer or substrate is performed to control viscosity, then filtration performance is maintained, but solution volume increases

Engineering Contradiction:

Improvefiltration performanceVSAvoidsolution volume

Core Design Contradiction:

ReliabilityVSVolume of stationary object

Solution Approach 1:

The system applies dilution selectively and partially rather than continuously. Dilution with buffer or substrate is performed only when viscosity reaches predetermined thresholds, using just enough diluent to restore optimal flow conditions. This partial action maintains filtration performance while minimizing unnecessary volume increase

Inventive Principle:

Principle #16Partial or excessive 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

This approach optimizes protein yield and process efficiency by maintaining filtration performance, reducing blockage, and controlling viscosity, thereby achieving higher protein recovery without negatively impacting subsequent purification steps.

Implementation Method 1

cross-flow filtration with microfiltration membranes is widely used and well known as an established separation process

Methodology Applied

Scientific EffectMicrofiltration: Filter (physical)

Implementation Method 2

Hollow fiber modules having ultrafiltration or microfiltration membranes are particularly suitable for cell separation using cross-flow filtration

Methodology Applied

Scientific EffectUltrafiltration: Semipermeable Membrane

Data Source

PatentUS20240279590A1Device arrangement and method of separating cells from a culture medium in a bioprocess

Publication Date: 2024.08.22 SARTORIUS STEDIM BIOTECH GMBH

AI summary

A device arrangement for separating cells from a culture medium in a bioprocess, in particular in a biopharmaceutical process, including a storage tank for the culture medium; a filtration module having a membrane adapted to be overflowed; an intake line connecting the storage tank to an unfiltrate inlet for supplying culture medium into the filtration module; a return line which connects a retentate-side outlet of the filtration module to the storage tank for returning retentate into the storage tank; a filtrate line which is connected to a permeate-side outlet of the filtration module for discharging filtrate; a first pump for maintaining a recirculation circuit; a backflush line which leads to a permeate-side connection and/or to the permeate-side outlet for supplying a rinsing liquid into the filtration module; and a second pump for conveying the rinsing liquid into the filtration module. A method of separating cells from a culture medium.