Two-Phase Sample Purification for Continuous Particle Separation
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Solution Overview
Problem
Existing biological sample purification systems are costly, time-consuming, and inefficient due to issues such as filter clogging, high maintenance requirements, and the need for multiple purification steps, which hinder the transition to continuous processing and scale-up for commercial production.
Innovation Solution
A two-phase buffer system using immiscible fluid phases with specific compositions to separate biological molecules from particulate contaminants through mixing and settling, allowing for continuous purification in a compact setup.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If centrifugation is used to remove cells and large particles, then purification effectiveness is improved, but cost and time consumption increase significantly
Solution Approach 1:
The invention extracts and removes the centrifugation step from the purification process, replacing it with direct filtration methods that achieve comparable purification effectiveness without the high costs and time consumption associated with continuous centrifugation systems
Solution Approach 2:
The patent employs disposable filters that can be easily replaced rather than expensive, maintenance-intensive centrifugation systems. These filters provide effective particle removal through their design that mimics centrifugation results without requiring continuous operation or complex mechanical systems
2Productivity
If depth filtration is used to eliminate centrifugation, then cost and time are reduced, but filter clogging and fouling increase
Solution Approach 1:
The filtration process is segmented into multiple stages with different filter pore sizes. A first filter with larger pores captures cells and large particles, while a second filter with smaller pores removes finer particulates. This segmentation prevents clogging of any single filter and maintains reliable operation throughout the process
Solution Approach 2:
The larger-pore filter acts as a preliminary filtering stage that removes bulk contaminants before the sample reaches the smaller-pore filter. This preliminary action protects the more sensitive second filter from clogging and extends its operational life
3Duration of action of stationary object
If filter pore size is increased to reduce clogging, then filter longevity is improved, but purification precision decreases
Solution Approach 1:
The purification task is divided into two sequential filtration stages, each with optimally sized pores for its specific function. The first stage uses larger pores for longevity and bulk particle removal, while the second stage uses smaller pores for high-precision filtering, achieving both goals simultaneously through system architecture
Solution Approach 2:
Instead of trying to find a single pore size that satisfies both longevity and precision requirements, the invention adds a dimensional element by using multiple filtration stages in series, transforming a single-parameter optimization problem into a multi-stage process where each stage optimizes for its specific function
4Manufacturing precision
If multiple filters are added to handle different particle sizes, then purification effectiveness is improved, but system complexity and expense increase
Solution Approach 1:
The patent merges the functions of multiple filtration stages into a integrated, sequential system where filters are arranged in a straightforward series configuration. This combining approach achieves comprehensive particle removal while maintaining relatively simple system architecture and operation compared to alternative multi-stage systems
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 system achieves high purity and yield of biological molecules with reduced time and cost by minimizing filter clogging and maintenance, enabling efficient continuous processing.
Implementation Method 1
A two-phase buffer system using immiscible fluid phases with specific compositions to separate biological molecules from particulate contaminants through mixing and settling
Implementation Method 2
A first portion of the mixed sample is disposed in a mixing compartment and is mixed to form an emulsion. The emulsion is then settled to separate the emulsion into a first phase and a second phase
Implementation Method 3
The settling compartment can include an acoustic settler configured to emit an acoustic wave into the settling compartment during settling of the emulsion
Implementation Method 4
A first portion of the mixed sample is disposed in a mixing compartment and is mixed to form an emulsion
Implementation Method 5
The emulsion is then settled to separate the emulsion into a first phase and a second phase
Implementation Method 6
The emulsion is then settled to separate the emulsion into a first phase and a second phase
Data Source
AI summary
Sample purification systems include a particle extraction assembly having a mixing compartment and a settling compartment. A biological sample is mixed with two liquid phases formulated to effectuate transfer of a biological molecule into a first phase and particulate contaminants into a second phase. The first phase includes a solubilizing salt, the second phase includes an organic molecule, and the mixture can have little or no monoatomic salt or dextran. The molecule-containing first phase can be optionally concentrated without also concentrating the particulate contaminants and introduced into a multi-stage liquid-liquid extractor, by which the biological molecule or molecular contaminants are extracted from the first phase into a third phase, thereby purifying the molecule away from contaminants. The extracted sample can be further purified through a series of processing steps. The system can be run in continuously mode to maintain sterility of the sample.