Polymer-Filled Chromatography Resin for High-Flow Biomolecule Separation
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Solution Overview
Problem
Current methods for purifying viruses, proteins conjugated to large particles, and other large biomolecules from smaller impurities are inefficient, requiring large columns, low flow rates, and limited sample loads, and have limited selectivity, making them costly and impractical for dense biomolecules.
Innovation Solution
A method of preparing a chromatography resin by adding a melted polymer to a chromatography resin, allowing it to absorb into the resin's pores, atomizing the mixture, and collecting polymer-filled beads to create a resin with multimodal properties without affecting selectivity or binding capacity, using a scalable and environmentally friendly process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If size exclusion chromatography (SEC) is used to purify large biomolecules, then separation based on size is achieved, but large columns are required, flow rates must be low, and sample loads are limited
Solution Approach 1:
The patent uses porous polymer beads as the chromatography medium, where the pore size distribution enables size-based separation. The porous structure allows small molecules to enter and be retained while large biomolecules are excluded and elute in the void volume, achieving both separation precision and higher flow rates without requiring large columns
Solution Approach 2:
The patent changes the physical parameters of the chromatography medium by using crosslinked polymer beads with controlled pore sizes. This allows optimization of both separation resolution and flow characteristics, enabling higher flow rates while maintaining separation precision through appropriate pore size selection
2Adaptability or versatility
If ion exchange chromatography (IEX) or hydrophobic interaction chromatography (HIC) is used, then charge or hydrophobic interactions are exploited, but selectivity is limited
Solution Approach 1:
The porous polymer beads provide size-based exclusion as the primary separation mechanism, which offers superior selectivity for large biomolecules compared to charge or hydrophobic interactions. The pore size can be tuned to specifically exclude target molecules while allowing impurities to enter and be retained
Solution Approach 2:
The size exclusion mechanism provided by porous beads is universally applicable to all large biomolecules regardless of their charge or hydrophobicity, providing broad versatility while maintaining high selectivity based on molecular size alone
3Measurement precision
If centrifugation is used to separate dense biomolecules, then density-based separation is achieved, but it can only be applied to large biomolecules that are relatively dense compared to the medium
Solution Approach 1:
The porous polymer beads enable separation based on molecular size through exclusion, which is applicable to all large biomolecules regardless of their density. This provides both high separation precision and broad applicability to viruses, protein conjugates, and other macromolecules that may not be dense enough for effective centrifugation
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 method produces a chromatography resin that effectively separates target molecules from contaminants while maintaining resin selectivity and binding capacity, allowing for efficient purification of protein-nanoparticle conjugates and viruses without clusters or organic solvents.
Implementation Method 1
adding a chromatography resin to a solution comprising a melted polymer while stirring to allow the melted polymer to absorb or otherwise enter the pores of the chromatography resin
Implementation Method 2
The solution is then atomized and insoluble porous polymer-filled chromatography resin beads are collected in a water bath
Data Source
AI summary
Methods of preparing polymer-filled chromatography resin and their uses are provided.