Acoustic Cell Segregation With Differentiation Vectors for Label-Free Sorting
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Solution Overview
Problem
Existing cell segregation methods suffer from low throughput, limited scalability, potential cell damage, and inefficiencies such as cell loss and the need for label-based approaches, particularly in techniques like FACS, DGC, MACS, and mechanical methods.
Innovation Solution
A method using acoustophoresis with differentiation vectors that attach to cells, generating acoustic waves to separate cells based on modified properties, allowing label-free, high-throughput, and scalable cell isolation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If FACS method is used for cell segregation, then cell specificity is improved, but cell damage and time consumption increase
Solution Approach 1:
The patent replaces the mechanical and chemical stressors of FACS (high-pressure fluid flow, fluorescent labeling) with acoustic field manipulation. Acoustic waves generate radiation pressure that sorts cells based on their intrinsic mechanical properties (compressibility, density) without physical contact or chemical modification, thereby maintaining cell specificity while eliminating cell damage and fluorescent labeling requirements.
Solution Approach 2:
The patent utilizes differences in physical parameters (compressibility, density, size) of target cells versus non-target cells to achieve separation. By tuning acoustic frequency and amplitude, the system exploits these inherent parameter differences to selectively manipulate target cells through acoustic radiation pressure, enabling specific segregation without external labels or mechanical stress.
2Ease of manufacture
If DGC method is used for cell segregation, then label-free sorting is achieved, but processing time increases and cell activation occurs
Solution Approach 1:
The patent replaces the time-consuming centrifugal force application in DGC with acoustic radiation pressure. The acoustic field generates sufficient force to manipulate cell positions and achieve separation based on density and compressibility differences, eliminating the need for prolonged centrifugation while maintaining label-free operation and reducing cell activation risks.
Solution Approach 2:
The patent employs periodic acoustic waves (ultrasonic frequencies) to achieve cell separation. The oscillating acoustic field creates time-averaged radiation pressure that continuously pushes cells toward acoustic nodes or anti-nodes based on their physical properties, enabling rapid separation through cyclic mechanical action rather than sustained centrifugal force.
3Measurement precision
If MACS method is used for cell segregation, then targeted cell isolation is improved, but purity decreases and washing steps are required
Solution Approach 1:
The patent replaces magnetic nanoparticle labeling and magnetic field manipulation with direct acoustic field manipulation. Acoustic radiation pressure acts on cells based on their intrinsic mechanical properties, eliminating the need for magnetic labels and subsequent washing steps. This approach achieves both high targeting specificity and high purity by separating cells based on their natural physical characteristics without contaminating label residues.
4Productivity
If mechanical or gravitational methods are used for cell separation, then scalability is improved, but cell damage and lack of specificity occur
Solution Approach 1:
The patent replaces crude mechanical or gravitational separation methods with precisely controlled acoustic field manipulation. The acoustic radiation pressure can be spatially and temporally modulated to achieve specific cell targeting while maintaining gentle, contactless manipulation. This enables scalable processing through parallel acoustic channel operation while preserving cell integrity and achieving high specificity through tuned acoustic parameters.
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
Enhances cell segregation efficiency, purity, and reduces cell damage by leveraging acoustic forces to differentiate cells with attached differentiation vectors, enabling efficient separation of rare cells without the need for additional washing steps.
Implementation Method 1
applying an acoustic field by generating acoustic waves inside the chamber
Implementation Method 2
The Applicant has found that this need could be met with a method using acoustic waves coupled with attachment of the cells to a differentiation vector
Data Source
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AI summary
The present invention relates to a method for segregating cells (2) and an acoustophoresis device (1) for implementing said method.