Radial Flow Chromatography Column for Direct Biomolecule Capture
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Solution Overview
Problem
Current chromatography systems face challenges in directly capturing biomolecules from unclarified cell culture liquids without causing cell damage or contamination, especially in industrial-scale applications, due to issues with bead packing, flow resistance, and shear forces, which lead to inefficient use and contamination of packed beds.
Innovation Solution
A radial flow packed bed chromatography column with a torus or doughnut-shaped packed bed design, featuring a larger inlet frit surface area than the outlet, ensures even distribution of liquid and minimizes shear forces, allowing for direct processing of unclarified cell culture liquids without intermediate filtration, reducing capital costs and product damage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fine particles are packed tightly and uniformly in the column to improve separation performance, then separation precision is improved, but flow resistance increases and shear forces increase causing cell damage
Solution Approach 1:
The patent changes the particle size parameter from fine particles to large beads (50-500 μm diameter), which reduces flow resistance and shear forces while maintaining separation precision through the radial flow configuration that distributes liquid evenly across the bed
Solution Approach 2:
The patent transitions from axial flow to radial flow configuration, changing the flow direction dimension. This radial flow through a torus-shaped packed bed distributes liquid horizontally across the entire bed cross-section, reducing vertical pressure gradients and shear forces on cells while maintaining effective separation
2Productivity
If unclarified cell culture liquid is processed directly to reduce processing steps and costs, then productivity is improved, but contamination risk increases
Solution Approach 1:
The patent changes the bead size parameter to large beads (50-500 μm) that create macro-pores in the packed bed, enabling whole cells to pass through without clogging while the affinity chromatography mechanism selectively captures target proteins, achieving both direct processing and contamination control
Solution Approach 2:
The patent uses porous affinity beads with controlled pore structures that allow cell passage while providing binding sites for target protein capture. The porous nature of both the large beads and the packed bed configuration enables direct processing of unclarified lysates without filtration steps
3Object-affected harmful factors
If large bead chromatography media is used to reduce shear forces and allow direct capture, then cell viability is improved, but flow distribution uniformity worsens
Solution Approach 1:
The patent changes the flow configuration from axial to radial direction. The radial flow distributes liquid horizontally across the entire packed bed cross-section, ensuring uniform flow distribution despite the presence of large beads, while maintaining low shear forces throughout the bed
Solution Approach 2:
The patent employs an asymmetric torus-shaped packed bed configuration with different inlet and outlet surface areas. The larger inlet surface area distributes flow evenly across the bed, while the smaller outlet surface area maintains sufficient flow velocity, creating optimal flow distribution uniformity throughout the asymmetric structure
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 design enables effective, contamination-free direct capture of biomolecules with improved cell viability and extended bed usage, reducing the risk of product digestion and contamination, while maintaining high flow rates and scalability.
Implementation Method 1
direct capture using large bead chromatography media
Implementation Method 2
fractionate the components with a fractionation or solid matrix... based upon such chemical criteria as ionic charge, hydrophobic nature, and the presence of certain chemical moieties such as antigenic determinants or lecithin-binding sites on the components, together characterized as 'affinity' moieties
Implementation Method 3
horizontal or radial flow type chromatographic columns... the sample/adsorption and elution/desorption fluids are introduced via a distributor to the outer periphery or circumferential wall or surface of the separating medium or matrix... and the fluids pass horizontally or radially inwardly through the separation medium
Implementation Method 4
pumping under pressure a liquid suspension of the particles into the column... the pumped liquid is able to pass through the filter element essentially unobstructed, the particles are retained by the filter element... As the column tube is filled, the particles are pressed out towards the wall of the tube and the particle bed obtains a stable compaction state with the particles well distributed by the pressure generated by the pump
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.