Bimodal Chromatography Media for Reduced Back Pressure

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Solution Overview

Problem

Chromatography media with desired binding capacity and efficiency often restrict high flow rates due to particle size and rigidity, leading to high back pressures, and increasing bead size to reduce back pressure results in lower resolution and dynamic binding capacity.

Innovation Solution

A method involving a mixture of small particles with a functionalized outer shell and a larger, non-functionalized or partially functionalized core, where the ratio of large to small beads is greater than 1.2, and the volume ratio is between 0.05-0.9, to reduce flow resistance while maintaining adsorption kinetics and elution efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stress or pressure

If larger size beads are used to reduce back pressures, then pressure drop decreases, but resolution and dynamic binding capacities are reduced

Engineering Contradiction:
Improveback pressureVSAvoidresolution
Core Design Contradiction:
Stress or pressureVSManufacturing precision

Solution Approach 1:

The chromatography media is segmented into two distinct particle size populations: small particles (10-50 μm) that provide high resolution and binding capacity, and large particles (50-200 μm) that reduce back pressure. This segmentation allows each size fraction to fulfill its specific function optimally within the packed bed

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the packed bed are assigned different particle sizes based on local functional requirements. Small particles are placed in regions where high resolution and binding capacity are critical, while large particles are positioned in regions where flow throughput and pressure management are prioritized

Inventive Principle:
Principle #3Local quality

2Stress or pressure

If larger size beads are used to reduce back pressures, then flow resistance decreases, but dynamic binding capacity is reduced

Engineering Contradiction:
Improveback pressureVSAvoiddynamic binding capacity
Core Design Contradiction:
Stress or pressureVSQuantity of substance

Solution Approach 1:

The chromatography media is segmented into two distinct particle size populations: small particles (10-50 μm) that provide high resolution and binding capacity, and large particles (50-200 μm) that reduce back pressure. This segmentation allows each size fraction to fulfill its specific function optimally within the packed bed

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention merges two particle size populations with complementary properties into a single chromatography media system. The small particles contribute binding capacity while the large particles contribute low flow resistance, and their combined effect achieves both high dynamic binding capacity and reduced back pressure simultaneously

Inventive Principle:
Principle #5Merging (Combining)

3Manufacturing precision

If small particles are used to maintain resolution and binding capacity, then chromatographic performance is improved, but back pressure increases

Engineering Contradiction:
ImproveresolutionVSAvoidback pressure
Core Design Contradiction:
Manufacturing precisionVSStress or pressure

Solution Approach 1:

The chromatography media is segmented into two distinct particle size populations: small particles (10-50 μm) that provide high resolution and binding capacity, and large particles (50-200 μm) that reduce back pressure. This segmentation allows each size fraction to fulfill its specific function optimally within the packed bed

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the particle size parameter from a uniform distribution to a bimodal distribution with specific size ranges. This parameter change transforms the pressure-flow characteristics while maintaining resolution, as the large particles provide flow channels that reduce back pressure without affecting the resolution provided by small particles

Inventive Principle:
Principle #35Parameter changes

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 optimizes column packing for reduced back pressure and preserved chromatographic performance, allowing higher sample loads without sacrificing resolution or binding capacity, thus enhancing pressure-flow characteristics.

Implementation Method 1

decrease the flow resistance in the packed bed

Methodology Applied
Scientific EffectPacked bed flow:

Implementation Method 2

small particles with the same type of functionalization (ligand) in the shell

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

The nature of the ligands is not limiting to the broad aspect of the present invention. Thus, in one embodiment of the present separation matrix, the ligands are selected from the group consisting of anion exchange ligands; cation exchange ligands; hydrophobic interaction chromatography (HIC) ligands; reversed phase chromatography (RPC) ligands; immobilised metal affinity chromatography (IMAC) ligands; thiophilic ligands; affinity ligands

Methodology Applied
Scientific EffectAffinity chromatography:

Data Source

PatentUS9259729B2Method for production of chromatography media
Publication Date: 2016.02.16 CYTIVA BIOPROCESS R&D AB
  • US9259729B2 patent drawing
  • US9259729B2 patent drawing
  • US9259729B2 patent drawing

AI summary

The present invention relates to a method and means to produce chromatography media having improved pressure-flow properties. More closely, the invention relates to bimodal particle size distribution and the use of layer functionalization as means to change pressure-flow properties of chromatography media. The invention relates to a method for production of chromatography media having improved pressure-flow properties, comprising mixing large beads/particles, comprising an inner core and an outer functionalized shell/lid, with smaller beads/particles, wherein the ratio of the particle size of large and small beads: [D50V for large particles/D50V for small particles]>1.2, and wherein the volume ratio of large and small beads in the column: [Total volume of large beads/Total volume beads] is in the range 0.05-0.9.