Nanofiltration Virus Removal via Ionic Strength and Macromolecule Additives
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Solution Overview
Problem
Current methods for purifying protein solutions, such as thrombin, are inadequate in removing infective particles like viruses and prions, particularly non-enveloped viruses and TSE agents, which can transmit serious diseases, and existing nanofiltration techniques have limitations in efficiency and protein recovery.
Innovation Solution
The method involves adding a biocompatible macromolecule, such as human albumin or dextran, to the protein solution before nanofiltration to enhance the removal of infective particles by leveraging concentration polarization and sieving properties of the nanofilter, thereby achieving high protein recovery and log reduction values.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nanofiltration is used to remove virus particles, then virus removal efficiency is improved, but protein recovery is reduced due to concentration polarization and membrane retention
Solution Approach 1:
The patent changes the ionic strength parameter of the buffer solution by adding salts (NaCl, KCl, MgCl2, CaCl2) to achieve saturation or near-saturation conditions. This parameter change reduces concentration polarization effects and minimizes protein retention on the membrane, thereby improving protein recovery while maintaining virus removal efficiency
Solution Approach 2:
The patent uses model viruses (parvovirus, hepatitis A virus) to replicate and study the behavior of different virus types during nanofiltration. By copying various virus characteristics in the model system, the researchers can optimize filtration conditions that apply to diverse viral contaminants without needing to test each virus type individually
2Duration of action of stationary object
If tangential flow nanofiltration is used to prevent protein buildup on membrane surface, then membrane fouling is reduced, but process complexity and equipment requirements increase
Solution Approach 1:
The patent employs dead-end filtration mode with high ionic strength buffer instead of tangential flow configuration. By changing the operational parameters (filtration mode and buffer composition), the patent achieves reduced membrane fouling and simplified equipment requirements while maintaining effective virus removal and protein recovery
3Device complexity
If dead-end nanofiltration is used to simplify the filtration process, then equipment complexity is reduced, but membrane fouling and virus removal efficiency deteriorate
Solution Approach 1:
The patent changes the buffer ionic strength to saturation levels and adds specific salts to the filtration buffer. This parameter change prevents protein concentration polarization and membrane fouling during dead-end filtration, thereby maintaining high virus removal efficiency (LRV > 4) while using simple equipment
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 results in high protein recovery rates (75-93%) and significant log reduction values (above 4 LRV) for infective particles, improving the efficiency of nanofiltration in removing viruses and prions from protein solutions while maintaining the integrity of the proteins.
Implementation Method 1
passing the solution through a nanofilter thereby obtaining a protein solution substantially purified from the infective particles
Implementation Method 2
the presence of protein increases the retention value of the model viruses in accordance with concentration polarization in which polarized protein adds an additional resistance to virus passage through the membrane
Data Source
Figure 1~2
AI summary
A method for purifying a protein solution from infective particles comprising (a) adding a macromolecule to the solution; and (b) passing the solution through a nanofilter. The macromolecule may be selected from a polymer of at least 3 monomers of sugars, amino acids, glycols, alcohols, lipids or phospholipids.