Synthetic Clarification Filter Layers for Low-TOC Protein Purification
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Solution Overview
Problem
Current clarification filters for cell culture clarification prior to chromatography and ultrafiltration suffer from high TOC release, batch-to-batch inconsistency, large void volumes, and low throughput, leading to product loss and increased impurity binding, especially with cellulose-based depth filters.
Innovation Solution
A filter system comprising multiple synthetic non-woven layers with decreasing pore sizes and a hydrophilic membrane layer, designed to remove large particles and protect downstream membranes from fouling, while minimizing TOC release and requiring minimal flushing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cellulose-based depth filters are used for cell culture clarification, then filtration capacity is achieved, but high TOC release and batch-to-batch inconsistency occur
Solution Approach 1:
The patent changes the material parameter from natural cellulose-based depth filter to synthetic non-woven filter material. This fundamental material parameter change eliminates the batch-to-batch inconsistency inherent in natural materials while maintaining filtration capacity through engineered pore structures and controlled porosity in the synthetic alternative.
Solution Approach 2:
The patent employs composite filter material consisting of synthetic non-woven layers combined with membrane layers. This composite structure integrates the high capacity of non-woven materials with the precision and consistency of membrane materials, achieving both high filtration capacity and reliable batch-to-batch performance.
2Productivity
If large surface area depth filters are used to handle large feed volumes, then filtration capacity increases, but void volume increases causing product loss and unspecific binding
Solution Approach 1:
The patent utilizes porous membrane layers with controlled pore sizes and optimized porosity. These porous structures provide high filtration capacity through engineered pore networks that minimize dead volumes and void spaces, reducing product retention and loss while maintaining the ability to handle large feed volumes.
Solution Approach 2:
The patent applies different filter materials with specific local properties to different functional requirements. The non-woven layers provide bulk filtration capacity, while the membrane layers provide precise separation with minimal void volume. This local optimization of material properties throughout the filter structure reduces overall product loss while maintaining high throughput.
3Reliability
If conventional depth filters with absorptive materials are used, then particle retention is achieved, but product binding increases requiring large flushing volumes
Solution Approach 1:
The patent changes the surface chemistry parameter of the filter material from absorptive natural cellulose to non-absorptive synthetic materials. This parameter change reduces unspecific binding of product molecules to the filter matrix, allowing smaller flushing volumes to recover product while maintaining effective particle and cell retention through physical filtration mechanisms.
Solution Approach 2:
The patent uses membrane layers that replicate the retention function of depth filters but with non-absorptive surfaces. These membrane layers copy the particle separation capability while eliminating the harmful absorptive properties, reducing product binding and minimizing the volume of flushing required for product recovery.
4Quantity of substance
If high cell density cell culture harvests are processed, then product concentration increases, but clarification and sterile filtration become more difficult
Solution Approach 1:
The patent divides the filtration function into multiple sequential layers: non-woven pre-filtration layers that handle bulk cell removal, followed by membrane layers that perform sterile filtration. This segmentation of filtration tasks allows each layer to be optimized for its specific function, making high cell density harvests easier to process while maintaining high product concentration.
Solution Approach 2:
The patent changes the pore size parameter progressively through the filter structure, from larger pores in non-woven layers to smaller pores in membrane layers. This graduated parameter change enables efficient processing of high cell density harvests by progressively reducing particle size requirements, reducing filtration resistance and making the process easier to operate while preserving product concentration.
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
The filter system achieves high filterability, low TOC release, and high throughput, enabling efficient removal of contaminants and maintaining target component concentration without additional concentration steps, with turbidity reduction exceeding 90%.
Implementation Method 1
Most of the cell components are removed from the liquid by filtration using a depth filter/clarification filter before chromatography and/or ultrafiltration
Implementation Method 2
a membrane layer having a fifth average pore size E, wherein the first average pore size A is from 15.0 μm to 50.0 μm, the second average pore size B is from 7.50 μm to 30.0 μm, the third average pore size C is from 5.00 μm to 15.0 μm, the fourth average pore size D is from 3.00 μm to 10.0 μm, and the fifth average pore size E is from 0.010 μm to 2.5 μm
Data Source
AI summary
The present invention relates to a filter system, which can be used as a clarification filter/depth filter for cell culture clarification before chromatography and/or ultrafiltration for protein purification, as well as to a method of separating cells and other contaminants from a fluid containing one or more target components by employing the filter system of the present invention.