Acoustic Particle Concentrator for High-Throughput Cell Isolation
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Solution Overview
Problem
Current methods for concentrating cells or particles into small volumes, such as those used in liquid biopsies, face challenges like sample loss, viability issues, and low volumetric throughput, especially when dealing with rare cell types like CTCs, which are difficult to isolate due to their low concentration and similarity to abundant background cells.
Innovation Solution
The development of a device employing field-based concentration techniques, including non-contact acoustic concentration and laminar flipping flow geometries, to focus and trap particles within a flow channel, allowing for high-throughput sorting and isolation of target cells into smaller volumes, utilizing acoustic and magnetic traps to accumulate particles at specific nodes or antinodes within the flow channel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If centrifugation or selective filtrations are used to concentrate cells or particles, then concentration is achieved, but sample loss occurs and viability of delicate cells is affected
Solution Approach 1:
The patent replaces mechanical concentration methods (centrifugation, filtration) with acoustic field-based concentration. Acoustic radiation pressure and acoustic streaming forces are used to manipulate and concentrate particles in a fluid stream without mechanical stress, thereby avoiding sample loss and maintaining cell viability while achieving high concentration factors.
Solution Approach 2:
The patent introduces an acoustic field as an intermediary mechanism between the sample and the concentration process. The acoustic field acts as a mediator that applies distributed forces to particles, enabling concentration without direct mechanical contact or stress, thus preventing sample loss and preserving delicate cells.
2Quantity of substance
If centrifugation is used to concentrate cells, then concentration is achieved, but operator variability increases and automation is difficult
Solution Approach 1:
The patent replaces manual mechanical operations (centrifugation requiring manual rotor handling, tube positioning) with an automated acoustic field generation system. The acoustic transducers can be precisely controlled and automated to concentrate particles consistently without operator intervention, eliminating variability and enabling full automation of the concentration process.
3Measurement precision
If immuno-labeled particles are used to target CTCs, then specific binding is achieved, but only cells expressing target ligands in sufficient numbers can be targeted
Solution Approach 1:
The patent replaces ligand-based specific binding with acoustic field-based separation. Acoustic radiation pressure and acoustic streaming forces enable separation of cells based on physical properties (size, density, compressibility) rather than surface ligand expression, allowing targeting of cells regardless of their ligand expression levels and expanding versatility to rare cell types.
Solution Approach 2:
The patent changes the separation parameter from biochemical (ligand-receptor binding) to physical (acoustic response properties). By manipulating acoustic parameters (frequency, amplitude, waveform) and cell physical properties (compressibility, density), the system can target diverse cell types including rare CTCs that may not express sufficient surface ligands for immuno-labeling approaches.
4Measurement precision
If negative selection protocols are used to purify target populations, then purity is improved, but greater concentration is required and protocol time increases
Solution Approach 1:
The patent replaces time-consuming dilutive concentration processes with rapid acoustic field-based concentration. Acoustic radiation pressure and acoustic streaming enable fast concentration of particles in the fluid stream without requiring extended dilutive steps, thereby reducing protocol time while achieving the necessary concentration for high-purity target population isolation.
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 enables efficient and high-resolution concentration of target particles or cells, reducing sample loss and operator variability, and allows for the isolation of rare cells like CTCs from whole blood, improving the sensitivity and efficiency of downstream analysis.
Implementation Method 1
a field generator configured to focus particles within the fluid sample into a focused stream
Implementation Method 2
generate a pressure node within the flow channel such that the particles accumulate in the pressure node
Implementation Method 3
a magnetic field generator configured to accumulate magnetic particles or magnetic materials associated with the particles at the channel wall within the analysis region
Implementation Method 4
laminar flipping flow geometries to focus and trap particles within a flow channel
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3C
AI summary
The present disclosure provides devices, systems and methods for concentrating particles after application of a field and flipping the direction of the particles. The field applied to the particles can be an acoustic field. The particles can be flipped from a first flow stream at a higher speed into a second flow stream at a lower speed to aid in concentrating the particles, including concentration within an analysis region.