Asymmetric Flow FFF Device with Encapsulated Membrane
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Solution Overview
Problem
Current analytical methods for fractionating nanoparticles and therapeutic proteins, such as Size Exclusion Chromatography (SEC) and Asymmetrical Flow-Field Flow Fractionation (AF4), face limitations including restricted size range, high back pressures leading to aggregate formation, and dilution effects, which hinder accurate characterization and throughput.
Innovation Solution
An asymmetric flow field-flow fractionation device with a semipermeable membrane mechanically held by encapsulation between layers, eliminating the need for a frit and reducing pressure, combined with thermoplastic elastomer layers for improved rigidity and reduced band broadening, allowing for smaller flow rates and enhanced particle separation efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If a frit is used to support the semipermeable membrane in AF4 devices, then the membrane is mechanically supported, but the device complexity increases and pressure is applied to the membrane causing potential rupture
Solution Approach 1:
The invention removes the frit component from the AF4 device structure, extracting the unnecessary element that caused mechanical support issues. The semipermeable membrane is directly mounted on the support plate without any frit layer, eliminating the complexity and pressure-related problems associated with frit support structures.
Solution Approach 2:
The support plate is designed to serve multiple functions: it provides structural support for the device, serves as the mounting surface for the semipermeable membrane, and eliminates the need for separate frit support. This multi-functional design simplifies the overall device structure while maintaining membrane support capability.
2Productivity
If high flow rates are used in analytical SEC, then separation speed increases, but dilution effects occur leading to disassembling of non-covalent aggregates
Solution Approach 1:
The invention optimizes the flow rate parameter to operate at lower velocities compared to traditional analytical SEC. This parameter change allows the system to maintain adequate separation speed while preventing excessive dilution of the sample, thereby preserving non-covalent aggregate structures during the separation process.
3Measurement precision
If high back pressures are applied in SEC, then separation efficiency increases, but aggregate formation is induced
Solution Approach 1:
The invention changes the pressure parameter by operating at lower back pressures compared to traditional SEC methods. This parameter modification maintains sufficient separation efficiency through optimized flow dynamics while avoiding the harmful effect of pressure-induced aggregate formation in the sample.
4Speed
If the fractionation channel has large cross-section for easy flow, then flow rate increases, but band broadening effects increase reducing separation efficiency
Solution Approach 1:
The invention employs an asymmetric flow field configuration where the fractionation channel has a specific cross-sectional geometry that is not uniform throughout. The channel dimensions are optimized to create asymmetric flow patterns that reduce band broadening while maintaining adequate flow rates, thereby improving separation efficiency without sacrificing speed.
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 device achieves improved separation efficiency and reduced band broadening, enabling more precise characterization of nanoparticles and proteins, including protein aggregates, with lower pressure and reduced dilution effects, thus enhancing analytical throughput and accuracy.
Implementation Method 1
the particles are pushed towards the membrane, but in the same time diffuse at different rates, particularly in the z relative direction in the fractionation channel 2, depending on the particle size. The size dependent diffusion makes the particles of different sizes to stabilize in different z
Implementation Method 2
A laminar flow is established in the fractionation channel 2, particularly in the x relative direction. Because of their different positions in the z relative direction, separated particles are carried by the mobile phase at different velocities due to the applied laminar flow
Implementation Method 3
The permeability of the membrane to liquid induces a cross flow through the membrane 10 and through the frit 27 from the fractionation channel 2 to the auxiliary channel 3. Due to the cross-flow, the particles 12 are pushed towards the membrane
Data Source
Figure 1~8A
Figure 8B~11A
Figure 11B~14
AI summary
The present invention relates to an asymmetric flow field-flow fractionation device (1) configured to separate a sample (8) of particles (12) dispersed in a liquid mobile phase (11), the device including a fractionation microchannel (2) comprising a sample inlet, a sample outlet, an auxiliary microchannel (3) comprising an auxiliary outlet, a semipermeable membrane (10) separating the fractionation microchannel (2) and the auxiliary microchannel (3), said membrane being permeable to liquid and being configured to maintain the particles (12) in said fractionation microchannel (2), the fractionation microchannel (2) being superimposed on the auxiliary microchannel (3), wherein the device (1) comprises two layers (19), each layer being with a microfabricated recess (14) which thickness (t) is less than 100IJm, the membrane (10) being mechanically held in between the two layers (19), the recesses (14) respectively defining the fractionation microchannel (2) and the auxiliary microchannel (3) on each side of the membrane (10).