Porous Microspheres for Chromatography

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Solution Overview

Problem

Conventional resin-based chromatographic columns face challenges with low binding capacity and high back pressure when processing macromolecules, leading to inefficient separation and productivity issues due to small, non-interconnected micropores that hinder large molecule diffusion and are prone to structural damage under high flow rates.

Innovation Solution

A stationary phase medium comprising cross-linked polymeric porous microspheres with interconnected macropores and multiple surface openings, allowing for a high specific surface area and convective transport, which maintains high binding capacity and low back pressure even at elevated flow rates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional resin beads with small micropores are used, then low molecular weight solutes can be separated effectively, but macromolecules cannot enter the pores resulting in low binding capacity

Engineering Contradiction:
Improvebinding capacity for macromoleculesVSAvoidpore structure complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent employs porous polymer beads with specifically engineered pore structures having diameters of 0.1-10 micrometers, which are large enough to accommodate macromolecules while maintaining adequate surface area for binding. The porous structure allows macromolecules to penetrate and bind effectively, resolving the contradiction between pore size and binding capacity.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent changes the pore size parameter from conventional nanometer-scale pores to micrometer-scale pores (0.1-10 μm), and adjusts the pore volume fraction to 0.3-0.8. These parameter changes enable macromolecule entry while maintaining binding capacity, directly resolving the size exclusion problem.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If high flow rates are used to increase productivity, then separation speed improves, but intra-bead diffusion becomes rate-limiting and resolution decreases

Engineering Contradiction:
Improveseparation speedVSAvoidseparation resolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent uses porous beads with large micrometer-scale pores and optimized pore volume fractions (0.3-0.8) that enable both fast convective flow through the beads at high rates and adequate diffusive transport for resolution. This dual-mode transport resolves the contradiction between speed and resolution.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

By changing the pore diameter to 0.1-10 μm and pore volume fraction to 0.3-0.8, the patent creates conditions where convective flow dominates at high rates while maintaining sufficient surface area for diffusive equilibration, enabling both high productivity and resolution.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If conventional resin beads are used, then adsorption chromatography can be performed, but back pressure increases due to limited convective flow between beads

Engineering Contradiction:
Improveflow rate capabilityVSAvoidback pressure
Core Design Contradiction:
Ease of operationVSStress or pressure

Solution Approach 1:

The patent employs porous beads with large micrometer-scale pores and optimized packing characteristics that facilitate both intra-bead convective flow and inter-bead fluid distribution. This reduces flow resistance and back pressure while maintaining high flow rate operation.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent changes bead size distribution, pore diameter (0.1-10 μm), and pore volume fraction (0.3-0.8) to optimize flow characteristics. These parameter changes reduce flow resistance and back pressure, enabling high flow rate operation with improved ease of use.

Inventive Principle:
Principle #35Parameter changes

4Area of stationary object

If small micropores are used in conventional resin beads, then surface area for adsorption is increased, but macromolecule diffusion into pores is hindered

Engineering Contradiction:
Improveadsorbing surface areaVSAvoidmacromolecule diffusion rate
Core Design Contradiction:
Area of stationary objectVSSpeed

Solution Approach 1:

The patent uses porous beads with micrometer-scale pores (0.1-10 μm) that are large enough for rapid macromolecule diffusion while maintaining high pore volume fractions (0.3-0.8) to provide sufficient adsorbing surface area. This resolves the contradiction between surface area and diffusion rate.

Inventive Principle:
Principle #31Porous materials

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 solution enables efficient separation of large biomolecules with stable binding capacity and reduced back pressure at high flow rates, overcoming the limitations of conventional chromatographic systems by facilitating convective mass transfer and maintaining mechanical strength.

Implementation Method 1

The respective porous microspheres are formed with interconnected macropores to constitute a porous network, which provides a large specific surface area as an adsorbing surface and facilitates convective mass transfer

Methodology Applied
Scientific EffectConvection: Convection

Implementation Method 2

Adsorption chromatography is a type of fluid chromatography for separation of a component in a mixture by selective adsorption from a mobile phase onto a solid stationary phase

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS20240033713A1Porous microspheres and stationary phase medium and chromatographic column comprising same
Publication Date: 2024.02.01 TANTTI LAB INC
  • US20240033713A1 patent drawing
  • US20240033713A1 patent drawing
  • US20240033713A1 patent drawing

AI summary

The invention relates to a stationary phase medium for adsorption chromatography, which is in form of porous microspheres suitable for being packed into a chromatographic column. The porous microspheres are made of cross-linked polymeric material and formed with interconnected macropores to constitute a porous network. The invented porous microspheres have a characteristic size ratio of porous network diameter to microsphere particle size, and the porous network is in fluid communication with the ambient via multiple openings, so that molecules are convectively transported through the porous network. Accordingly, the invention shows low back pressure and high binding capacity to molecules at high mobile phase velocities.