Continuous Protein Separation via Ultrafiltration
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Solution Overview
Problem
Current continuous perfusion fermentation processes face challenges such as yield losses and quality reduction due to prolonged product residence time, high capital costs for cold storage, low volumetric throughput, logistical difficulties with varying process volumes, and non-sterile operation, which lead to rejected batches and increased costs.
Innovation Solution
A continuous and integrated protein separation process that maintains a specific flow rate below the transition point of the protein in the pressure-dependent region of the flux versus transmembrane pressure curve, using ultrafiltration or convective adsorption/desorption systems to produce a sterile, particle-free, concentrated, and partially purified product isolate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If batch isolation process is used after continuous perfusion fermentation, then product can be concentrated and purified, but product residence time is prolonged causing yield losses and quality reduction
Solution Approach 1:
The patent merges the continuous perfusion fermentation process with the isolation and concentration processes into a single integrated continuous system. The harvest stream is continuously fed through ultrafiltration and chromatography columns without batch interruptions, eliminating the time loss associated with batch processing while maintaining product purification quality.
Solution Approach 2:
The invention implements continuous operation where the protein separation process runs continuously without batch stops. The system maintains steady-state operation through continuous feeding of harvest stream and continuous removal of purified product, ensuring uninterrupted processing that minimizes residence time while achieving desired purification.
2Productivity
If batch processing is used for isolation, then equipment requirements are reduced, but volumetric throughput is low and capital costs increase
Solution Approach 1:
The system enables continuous processing of the harvest stream through ultrafiltration and chromatography columns, maintaining steady-state operation that maximizes volumetric throughput. The continuous operation allows the equipment to operate at optimal capacity without batch interruptions, significantly increasing productivity compared to batch processing.
Solution Approach 2:
The continuous processing system is designed to handle varying process volumes flexibly. The system can process different harvest volumes continuously without requiring separate batch processing equipment, making the continuous system universally applicable to different production scales and reducing overall capital requirements.
3Adaptability or versatility
If harvest is collected and stored in large volumes, then processing flexibility is improved, but cold storage capital costs and product degradation increase
Solution Approach 1:
The system performs concentration and purification actions continuously during the harvest process itself, rather than collecting large volumes for later processing. By preliminarily concentrating and purifying the product continuously, the system eliminates the need for large-volume cold storage while maintaining processing flexibility.
Solution Approach 2:
The continuous processing system eliminates interruptions between harvest collection and processing. The harvest stream is continuously fed through separation columns without batch accumulation, removing the need for cold storage infrastructure and associated energy costs while maintaining operational flexibility.
4Speed
If conventional ultrafiltration is used at high flux, then processing speed increases, but concentration polarization and gel layer formation reduce membrane performance
Solution Approach 1:
The system operates ultrafiltration at controlled, moderate flux rates rather than maximum flux. By optimizing the flux parameter to operate below the transition point, the system maintains stable membrane performance without concentration polarization or gel layer formation, while still achieving high overall productivity through continuous operation.
Solution Approach 2:
The continuous operation allows the membrane to work consistently at optimized flux rates without the intermittent high-stress conditions of batch processing. The continuous feed and permeate removal maintain steady-state conditions that prevent membrane fouling while maximizing processing speed over extended periods.
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 minimizes product residence time, reduces capital and labor costs, enhances yield and quality, and allows for continuous sterile operation, addressing the limitations of batch processes and improving the efficiency and sterility of protein purification.
Implementation Method 1
filtering a heterogeneous clarified fluid mixture by continuous ultrafiltration at a specific flow rate below the transition point of the molecule of interest in the pressure-dependent region of the flux versus transmembrane pressure (TMP) curve
Implementation Method 2
convective adsorption/desorption systems to produce a sterile, particle-free, concentrated, and partially purified product isolate
Implementation Method 3
convective adsorption/desorption systems to produce a sterile, particle-free, concentrated, and partially purified product isolate
Data Source
AI summary
The present invention relates to a process and apparatus for purifying a molecule of interest from a heterogeneous clarified fluid mixture. The apparatus of the invention generally comprises a continuous perfusion fermentation system, a continuous particle removal system integrated with the perfusion fermentation system; and a continuous purification system integrated with the particle removal system, which is maintained under sterile conditions. The process comprises filtering a heterogeneous clarified fluid mixture by continuous ultrafiltration at a specific flow rate below the transition point of the molecule of interest in the pressure-dependent region of the flux versus TMP curve, wherein the specific flow rate is maintained substantially constant throughout the continuous ultrafiltration.