Segmented Continuous Flow for Virus Inactivation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current protein purification processes, especially for therapeutic proteins like monoclonal antibodies, face challenges in achieving efficient virus inactivation due to prolonged residence times in large tanks, leading to potential protein degradation and aggregation, and are not amenable to continuous processing.
Innovation Solution
The method involves maintaining narrow residence time distributions in continuous flow systems by separating fluid into discrete zones within an axial flow channel, allowing for efficient virus inactivation without the need for large tanks, using materials like circular plastic tubing or Smart FLEXWARE macro fluidic flow path assemblies, and incorporating virus inactivation agents directly in the flow channel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If material is held in a large tank for virus inactivation, then complete virus inactivation is achieved, but processing time is excessively long and protein degradation occurs
Solution Approach 1:
The patent divides the fluid stream into discrete packets using mechanical compression in a flow channel. This segmentation allows each packet to be independently processed with a controlled, narrow residence time distribution, eliminating the need for prolonged holding in large tanks while ensuring complete virus inactivation through precise timing.
Solution Approach 2:
The system transitions from static batch processing in tanks to dynamic continuous flow processing. The mechanical compression and release of flow channels creates dynamic packet formation and movement, enabling controlled residence times that are sufficient for virus inactivation but significantly shorter than traditional batch methods.
2Reliability
If material is held in a large tank for virus inactivation, then virus inactivation is achieved, but protein degradation and aggregation increase
Solution Approach 1:
By segmenting the fluid into discrete packets with narrow residence time distributions, the system ensures that all protein molecules experience approximately the same residence time. This eliminates the wide distribution of exposure times in batch processing, preventing both insufficient inactivation and excessive exposure that causes degradation.
Solution Approach 2:
The continuous flow system maintains constant movement of fluid packets through the processing channel, ensuring uniform and consistent exposure to inactivation conditions. This continuous action with controlled residence time prevents the variable exposure periods that lead to protein degradation in batch processes.
3Reliability
If traditional batch processing with large tanks is used, then virus inactivation is achieved, but the process is not amenable to continuous processing
Solution Approach 1:
The patent implements continuous processing by segmenting the continuous flow into discrete packets that can be individually timed and controlled. This segmentation allows the system to maintain continuous operation while ensuring each packet receives the precise residence time needed for virus inactivation, bridging the gap between batch reliability and continuous efficiency.
Solution Approach 2:
The system replaces the mechanical mixing and holding approach of batch tanks with a flow-based mechanical compression and release system. This substitution enables continuous processing while maintaining the controlled exposure conditions necessary for reliable virus inactivation.
4Reliability
If large holding tanks are used for virus inactivation, then sufficient residence time is ensured, but system size and space requirements increase
Solution Approach 1:
By segmenting the fluid into packets with narrow residence time distributions, the system achieves reliable minimum residence time assurance without requiring large tank volumes. Each packet's residence time is precisely controlled by the compression and release timing, eliminating the need for oversized tanks to account for wide residence time distributions.
Solution Approach 2:
The dynamic control of packet formation and movement through mechanical compression allows the system to achieve the required residence times in a compact flow channel rather than a large static tank. The residence time is controlled by the timing and duration of compression cycles rather than by tank size.
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 reduces the overall time and space required for virus inactivation, ensures all molecules receive sufficient inactivation, minimizes protein degradation, and facilitates continuous processing by maintaining narrow residence time distributions, thereby enhancing the efficiency and reliability of the purification process.
Implementation Method 1
The flow involved in mAb processing typically falls into the laminar flow regime (Reynolds number less than 2100). In this regime, molecules disperse due to radial diffusion and as a result, a solute pulse spreads axially along the direction of flow.
Implementation Method 2
In this regime, molecules disperse due to radial diffusion and as a result, a solute pulse spreads axially along the direction of flow.
Implementation Method 3
This is known as Taylor dispersion, and is illustrated schematically in FIG. 1. Poiseuille flow for laminar flow leads to a parabolic velocity profile. The leading and trailing ends of the pulse begin as sharp interfaces but become parabolic in shape due to the laminar flow of the fluid.
Implementation Method 4
One virus inactivation process involves a large holding tank where material is held at inactivation conditions, such as low pH and/or exposure to detergent, for 60 minutes.
Implementation Method 5
This may be through the addition of acid to achieve a low pH target level or it may be through the addition of detergent in a detergent-based inactivation process.
Data Source
AI summary
Methods of maintaining narrow residence time distributions in continuous flow systems, particularly applicable to virus inactivation such as during a protein purification process. Fluid sample is introduced into an axial flow channel and caused to flow therein in discrete packets or zones to minimize residence time distribution and axial dispersion. Embodiments described herein obviate or minimize the need for using large tanks or reservoirs for performing virus inactivation during a protein purification process; reduce the overall time required for virus inactivation, and/or reduce the overall physical space required to perform the virus inactivation operation during a protein purification process, which in turn reduces the overall footprint for the purification process.