Stir Cell Filtration for Hydrogel Particle Size Control

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Solution Overview

Problem

Polymeric particles, particularly hydrogel particles, exhibit significant variance in size due to their deformable nature, leading to inefficiencies in separation techniques such as chromatography and magnetic separation, as well as polynucleotide capture methods, resulting in inconsistent interaction sites and reduced capture or separation efficiency.

Innovation Solution

A filtration system utilizing a stir cell with filters of varying pore sizes and controlled flow rates to selectively retain or pass particles, maintaining a low coefficient of variance in particle size distribution by adjusting permeate velocities across the filters, allowing for the separation of particles with desired average sizes and narrow size distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polymeric particles are used in separation techniques, then separation capability is provided, but variance in particle size leads to variance in particle weight and number of reaction sites, reducing separation efficiency

Engineering Contradiction:
Improveseparation efficiencyVSAvoidparticle size uniformity
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by systematically varying filtration conditions including pore size (from 0.22 µm to 5 µm), flow rates (from 0.1 to 10 mL/min), and filtration stages to achieve narrow particle size distribution (coefficient of variation <5%). This resolves the contradiction by transforming the particle population from polydisperse to monodisperse through controlled parameter adjustments during filtration.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If larger pore size filters are used, then filtration speed increases, but particles of varying sizes may pass through, reducing separation precision

Engineering Contradiction:
Improvefiltration speedVSAvoidparticle size control
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent segments the filtration process into multiple sequential stages using filters with progressively optimized pore sizes. Each stage targets specific particle size ranges, with flow rates adjusted for each stage. This segmentation allows high flow rates to be used in early stages with larger pores, while later stages use smaller pores with lower flow rates to achieve precise size control, thus resolving the contradiction between speed and precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs dynamic adjustment of flow rates across different filtration stages. Flow rates are optimized for each pore size and particle concentration level, allowing the system to adapt to changing conditions during filtration. This dynamic control maintains high productivity while ensuring precise particle size selection, resolving the contradiction between filtration speed and size control.

Inventive Principle:
Principle #15Dynamics

3Manufacturing precision

If multiple filtration stages are used to reduce particle size variance, then particle size uniformity improves, but process complexity increases

Engineering Contradiction:
Improveparticle size uniformityVSAvoidfiltration system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent employs a universal filtration approach where a single multi-stage filtration system performs multiple functions: initial particle concentration, size-based separation, and final monodispersity achievement. The same basic filtration apparatus is used across all stages with only pore size and flow rate parameters changed, rather than requiring different specialized devices for each function. This universality reduces overall system complexity while achieving high particle size uniformity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 method effectively reduces the coefficient of variance in particle size to less than 5%, enhancing the efficiency of separation techniques by ensuring consistent interaction sites and improving the accuracy of particle capture or separation, even when using filters with pore sizes greater than the desired average particle size.

Implementation Method 1

filtering a plurality of polymeric particles through a first filter having a pore size at a first permeate velocity to provide a first subset of polymeric particles

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 2

drawing a permeate from the permeate side of the filter using a pump at a first flow rate

Methodology Applied
Scientific EffectPressure-driven flow: Pressure Gradient

Data Source

PatentUS9932448B2Purification systems and methods
Publication Date: 2018.04.03 LIFE TECHNOLOGIES CORP
  • US9932448B2 patent drawing
  • US9932448B2 patent drawing
  • US9932448B2 patent drawing

AI summary

A method of preparing hydrogel particles includes applying a solution including a plurality of hydrogel particles to a stir cell. A retentate side of a filter defines a lower surface of the stir cell. The filter has the retentate side and a permeate side. The method further includes, while stirring the solution within the stir cell, dispensing a buffer solution at a first flow rate to the stir cell and drawing a permeate from the permeate side of the filter using a pump at a second flow rate, the permeate including a subset of the plurality of hydrogel particles.