Microfluidic Cell Deformability Measurement via Ultrasonic Acoustic Radiation
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Solution Overview
Problem
Current methods for measuring cellular deformability are time-consuming, unable to process large numbers of cells in real-time, and are not suitable for point-of-care solutions, as they require high-speed imaging and cannot sort cells effectively.
Innovation Solution
A microfluidic device with a cell probing chamber that uses ultrasonic waves to deform cells, allowing for slower imaging systems and the ability to sort cells post-deformation testing, reducing costs and enabling real-time analysis of individual cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high-speed imaging systems are used to measure cellular deformability, then measurement precision is improved, but device complexity and cost increase
Solution Approach 1:
The patent replaces high-speed mechanical/optical imaging systems with an acoustic field-based measurement approach. By using acoustic radiation force to deform cells and measuring the resulting oscillations through simpler optical means, the system achieves accurate deformability measurements without requiring complex high-speed imaging infrastructure
Solution Approach 2:
The patent changes the measurement parameter from direct high-speed imaging of cell deformation to measurement of oscillation frequency and damping characteristics. This parameter transformation allows using slower, simpler imaging systems while maintaining measurement precision through analysis of temporal oscillation patterns rather than spatial deformation rates
2Measurement precision
If traditional rheological phenotyping methods are used, then measurement accuracy is maintained, but productivity decreases due to inability to process large numbers of cells in real-time
Solution Approach 1:
The patent implements a high-throughput workflow where cells are processed individually through a microfluidic channel one at a time, with each cell trapped, measured, and released in sequence. This segmentation approach maintains measurement accuracy for each cell while enabling continuous processing of large cell populations, achieving both precision and productivity
Solution Approach 2:
The patent establishes continuous cell processing through automated trapping and release cycles. The acoustic trap continuously captures cells, performs measurements, and releases them for collection, creating an uninterrupted workflow that processes cells in real-time without batch processing delays, thereby maintaining both accuracy and high throughput
3Measurement precision
If current deformability measurement methods are used, then single-cell analysis is possible, but loss of time increases due to inability to sort cells effectively
Solution Approach 1:
The patent performs preliminary sorting of cells based on deformability characteristics during the measurement process itself. By trapping and measuring cells sequentially, the system identifies cells of interest (e.g., circulating tumor cells) and directs them to appropriate collection channels before final processing, eliminating the need for time-consuming post-analysis sorting
Solution Approach 2:
The patent introduces an acoustic radiation force trap as an intermediary mechanism between cell detection and cell sorting. This acoustic trap serves as a temporary holding and classification station that can selectively retain or release cells based on their deformability measurements, enabling rapid sorting decisions without physical manipulation delays
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 cost-effective rheological phenotyping of cells, allowing for the analysis of large cell populations in a timely manner and facilitating point-of-care applications by using slower imaging systems and integrating cell sorting mechanisms.
Implementation Method 1
By applying a standing pressure wave to the cell within the cell probing chamber
Implementation Method 2
The apparatus may include a plurality of piezoelectric elements disposed on opposing sides of the lateral fluidic channel
Data Source
AI summary
An example method for measuring deformability of a cell, consistent with the present disclosure, includes detecting a single cell of a biologic sample in a cell probing chamber of a microfluidic device. The method includes isolating the cell in the cell probing chamber of the microfluidic device by terminating the flow of the biologic sample through the microfluidic device. The method further includes causing deformation of the cell by introducing ultrasonic waves into the cell probing chamber, and measuring deformability of the cell responsive to the introduction of the ultrasonic waves.