Multimodal Membrane Separation Matrix for High-Flow Biomolecule Purification
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Solution Overview
Problem
Current chromatography methods for biomolecule purification face challenges in achieving high binding capacity at high flowrates, leading to inefficient productivity due to the limitations of porous bead-based systems and monolith/membrane materials.
Innovation Solution
A separation matrix with multimodal ligands covalently coupled to a nonwoven polymer fiber membrane support, allowing for high selectivity and rapid biomacromolecule separations through convective flow, including methods for bind-elute and flow-through separations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If porous bead-based chromatography is used to achieve high binding capacity, then binding capacity is improved, but residence time increases and productivity decreases
Solution Approach 1:
The patent employs a porous monolith structure with controlled pore size and distribution to enable rapid convective flow while maintaining high surface area for binding. The porous architecture allows biomolecules to be transported quickly through the matrix via convection rather than diffusion, achieving both high binding capacity and short residence times (typically 0.2-0.5 minutes), thereby resolving the contradiction between capacity and productivity.
Solution Approach 2:
The invention uses composite materials combining the monolith support structure with immobilized ligands or antibodies. This composite approach integrates the mechanical stability and convective flow characteristics of the monolith with the high-specificity binding properties of the ligands, achieving both high binding capacity and rapid processing speeds that improve overall productivity.
2Productivity
If residence time is reduced to increase productivity, then productivity is improved, but binding capacity drops off rapidly
Solution Approach 1:
The patent replaces the diffusion-based binding mechanism of traditional porous beads with a convection-dominated transport mechanism in the monolith structure. This mechanical substitution allows biomolecules to be rapidly transported through the matrix by bulk flow, enabling binding events to occur efficiently even at residence times of 0.2-0.5 minutes, thereby maintaining high binding capacity while dramatically improving productivity.
3Productivity
If high flowrates are used to reduce residence time, then productivity is improved, but mechanical instability of porous beads causes compression or collapse
Solution Approach 1:
The patent employs a monolith structure that can be viewed as a continuous, integrated framework rather than discrete porous beads. This monolithic architecture provides superior mechanical stability and structural integrity, allowing the material to withstand high flowrates and pressures without compression or collapse, thereby enabling high productivity operations while maintaining reliability.
4Quantity of substance
If conventional chromatography materials are used to achieve high binding capacity, then binding capacity is improved, but flowrate is limited due to diffusion dependency
Solution Approach 1:
The patent fundamentally changes the transport parameter from diffusion-dominated (in traditional porous beads) to convection-dominated (in the monolith structure). This parameter change enables the system to operate at much higher flowrates while maintaining efficient binding, as convective transport is far less sensitive to flow rate variations than diffusion-based processes, thereby resolving the contradiction between binding capacity and flowrate.
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 matrix achieves high binding capacity and selectivity, enabling efficient purification of biomacromolecules with reduced residence time and increased productivity, overcoming the limitations of conventional chromatography materials.
Implementation Method 1
Such chromatographic separations involve binding of i) the target molecule and/or, ii) one or more impurities, to a solid phase when a liquid phase containing the target molecule and impurities is contacted with the solid phase. The interaction between target molecule/impurities and the solid phase can be based on charge, hydrophobicity, affinity or a combination thereof.
Implementation Method 2
The flow through such materials is convective rather than diffusional, and their binding capacity is therefore far less sensitive to flow than porous bead-based systems.
Data Source
AI summary
The invention discloses a separation matrix comprising a plurality of multimodal ligands covalently coupled to a support, wherein said support is a membrane comprising nonwoven polymer fibers and wherein said ligands are capable of interacting with a target biomacromolecule. Further, the invention discloses separation methods using the separation matrix.