Depth Filter Media for Primary Clarification of High-Solids Bioprocess Feeds
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Solution Overview
Problem
Current primary clarification processes for cell culture harvests and high-solids feedstocks, particularly for monoclonal antibodies, face challenges with high turbidity and low throughput due to the use of centrifugation or tangential flow microfiltration, leading to increased costs, cross-contamination risks, and inefficiencies in removing particulates and cellular debris.
Innovation Solution
A primary clarification depth filtration process that utilizes a depth filtration device without a centrifugation or tangential flow microfiltration step, employing a porous depth filter media to separate biomolecules from cellular debris and colloidal particulates, with a focus on chemically flocculated feeds to enhance throughput and reduce contamination risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If centrifugation or tangential flow microfiltration is used for primary clarification, then cell mass and larger cellular debris can be removed, but the process becomes complex, time-consuming, and prone to cross-contamination
Solution Approach 1:
The patent combines the functions of primary clarification and secondary filtration into a single depth filter cartridge, eliminating the need for separate centrifugation or microfiltration steps. The depth filter media is designed to simultaneously capture both large cellular debris and smaller particulates in one pass, simplifying the overall process while maintaining clarification efficiency.
Solution Approach 2:
The patent extracts the clarification function from complex mechanical separation systems (centrifuges, microfiltration devices) and implements it through a simpler depth filtration mechanism. The depth filter cartridge serves as a standalone primary clarification device, removing the need for additional clarification steps and reducing process complexity.
2Reliability
If centrifugation is used for primary clarification, then cellular debris can be removed, but throughput is reduced and processing time increases
Solution Approach 1:
The patent changes the filtration parameters by using depth filter media with varying pore sizes and depths, allowing for higher flow rates while maintaining clarification quality. The depth filter design enables turbulent flow conditions that enhance throughput compared to the laminar flow typical of microfiltration, while still achieving effective particle removal.
3Reliability
If multiple filtration steps are used, then product quality can be maintained, but operational costs and cross-contamination risks increase
Solution Approach 1:
The patent merges multiple filtration functions into a single depth filter cartridge that can be completely replaced between batches. This disposable design eliminates cross-contamination risks associated with cleaning and reusing filtration equipment, while maintaining product quality through consistent filtration performance across multiple process steps.
4Device complexity
If depth filtration is used without prior centrifugation, then process complexity is reduced, but filter loading capacity must be sufficient for high solids content
Solution Approach 1:
The patent employs depth filter media with specifically engineered porous structures that have high void volumes and appropriate pore size distributions. These porous materials can accommodate high solids content feeds without rapid clogging, enabling direct depth filtration of cell culture harvests without prior centrifugation while maintaining process simplicity.
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 improves the clarification efficiency and throughput of high-solids feedstreams by effectively filtering particles between 0.5 μm to 200 μm, reducing the need for additional filtration steps and minimizing cross-contamination, while maintaining high product quality and reducing operational costs.
Implementation Method 1
contacting the porous depth filter media with the feed stream, such that the depth filter media is capable of filtering cellular debris and particulates having a particle size distribution of about 0.5 μm to about 200 μm
Implementation Method 2
separating the target biomolecule of interest from the cellular debris and particulates
Data Source
AI summary
A process for the primary clarification of feeds, including chemically treated flocculated feeds, containing the target biomolecules of interest such as mAbs, mammalian cell cultures, or bacterial cell cultures, using a primary clarification depth filtration device without the use of a primary clarification centrifugation step or a primary clarification tangential flow microfiltration step. The primary clarification depth filtration device contains a porous depth filter having graded porous layers of varying pore ratings. The primary clarification depth filtration device filters fluid feeds, including chemically treated flocculated feeds containing flocculated cellular debris and colloidal particulates having a particle size distribution of approximately about 0.5 μm to 200 μm, at a flow rate of about 10 litres/m2/hr to about 100 litres/m2/hr. Kits and methods of using and making the same are also provided.