Radial Flow Chromatography Column with Large Beads for Direct Capture
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Solution Overview
Problem
Existing chromatography systems face challenges in efficiently capturing biomolecules from unclarified process liquids without causing cell damage or contamination, especially at industrial scales.
Innovation Solution
The implementation of a radial flow packed bed chromatography column with large beads and a torus-shaped packed bed design, which allows for even distribution of the liquid and minimizes cell damage, enabling direct capture of biomolecules from unclarified process liquids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If clarification steps are used to clean process liquid before chromatography, then capture efficiency is improved, but capital costs and setup time increase
Solution Approach 1:
The invention extracts and removes the clarification step from the traditional chromatography process sequence. By using large bead chromatography media with sufficient porosity and flow distribution, the system directly captures biomolecules from unclarified process liquid, eliminating the need for separate filtration or centrifugation units and reducing overall process complexity.
Solution Approach 2:
The large bead chromatography media performs multiple functions simultaneously: it acts as both the capture medium and the flow distributor. The beads' physical properties (size, porosity, surface area) enable them to handle unclarified liquid while maintaining effective biomolecule capture, combining what were previously separate process functions into a single step.
2Reliability
If traditional packed bed chromatography is used, then biomolecule capture is achieved, but cell damage and contamination occur
Solution Approach 1:
The invention changes the local quality of the chromatography medium by using large beads (50-500 μm) instead of fine particles. This local change in bead size creates sufficient inter-particle space and reduces flow velocity at the bead surface, preventing cell damage while maintaining capture efficiency through the beads' high surface area and porosity.
Solution Approach 2:
The large bead chromatography media utilizes porous materials with controlled porosity to achieve effective biomolecule capture from unclarified liquid. The porous structure allows cells to pass through without damage while enabling biomolecules to be captured on the bead surfaces, preventing contamination while maintaining capture reliability.
3Measurement precision
If fine particles are used in chromatography column, then separation efficiency is improved, but flow distribution becomes uneven and pressure increases
Solution Approach 1:
Instead of using fine particles to achieve separation efficiency, the invention inverts the approach by using large beads. The large bead size naturally provides better flow distribution and lower pressure, while the beads' porosity and surface area compensate for the reduced particle count, maintaining separation efficiency without the harmful pressure effects.
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 solution achieves effective and contamination-free direct capture of biomolecules, reducing capital costs and setup time, while maintaining cell viability and preventing product damage.
Implementation Method 1
direct capture using large bead chromatography media... capture of product from crude feed... fractionate the components of a mixture based upon such chemical criteria as ionic charge, hydrophobic nature, and the presence of certain chemical moieties... characterized as 'affinity' moieties
Data Source
AI summary
Disclosed is a continuous process in which a subset of a number of mutually identical columns, are connected in series. The process liquid, e.g. crude cell culture harvest, is supplied to the most upstream column of the subset. It flows successively through the in series connected columns and leaves the subset through the most downstream and flows into the downstream collection vessel. As soon as the packed bed of the most upstream column is become saturated with product, this column is disconnected from the subset. It is removed from the series connection. A replacement, identical, column is added such that it is connected in series downstream from the most downstream column of the subset. This process is repeated.