Acoustic Force Spectroscopy for Cell Compressibility Measurement
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Solution Overview
Problem
Current methods for determining cell compressibility using acoustophoresis are complex, require precise knowledge of microfluidic flow channels, and are prone to errors due to assumptions, making them unsuitable for accurate, high-throughput characterization of heterogeneous cell populations.
Innovation Solution
A method using acoustic force spectroscopy that involves analyzing images of cellular bodies subjected to acoustic force pulses, tracking their trajectories, and determining densities and velocities to calculate compressibility without complex modeling, allowing for robust classification and sorting of cells based on size, density, and compressibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If acoustophoresis method with multi-frequency 3D acoustic force field is used to determine cell compressibility, then cell compressibility can be measured, but the method requires complex handling of cells, complex modeling and fitting, precise knowledge of microfluidic flow channel, and produces large computational effort
Solution Approach 1:
The patent segments the measurement process into two distinct phases: (1) sedimentation phase where cells settle under gravity without acoustic forces, and (2) acoustic force application phase where acoustic forces act on settled cells. This segmentation eliminates the need for complex multi-frequency 3D acoustic fields and allows independent measurement of sedimentation velocity and acoustic response, significantly reducing modeling and computational complexity while maintaining measurement precision
Solution Approach 2:
The patent applies preliminary action by first allowing cells to settle and attach to the substrate under gravity before applying acoustic forces. This preliminary sedimentation step simplifies the subsequent acoustic measurement by ensuring cells are in a known, stable position, eliminating the need for complex real-time tracking and modeling of cell positions during the measurement process
2Measurement precision
If acoustophoresis method with two horizontal acoustic fields is used, then cell compressibility can be determined, but precise knowledge of microfluidic flow channel and acoustic fields is required, introducing vulnerabilities to practical deviations and larger errors
Solution Approach 1:
The patent inverts the conventional approach by applying acoustic forces in the vertical direction (perpendicular to the substrate) rather than using horizontal acoustic fields. This inversion allows measurement of cell mechanical properties directly from the vertical displacement of settled cells, eliminating the need for precise knowledge of horizontal flow channel geometry and acoustic field distributions, thereby reducing vulnerability to practical deviations and improving reliability
3Productivity
If different cell parameters such as density and compressibility are determined by fitting a single measurement, then measurement can be performed, but entanglement results in reduced fitting precision
Solution Approach 1:
The patent segments the parameter determination process by measuring density through gravitational sedimentation velocity in the absence of acoustic forces, and measuring compressibility through the acoustic response of settled cells. This segmentation separates the determination of different cell parameters into independent measurements, eliminating the entanglement that reduces fitting precision while maintaining measurement efficiency
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
Enables accurate and efficient determination of cell compressibility and classification, reducing errors and computational complexity, and facilitating the sorting of cellular bodies in heterogeneous populations.
Implementation Method 1
manipulation including exerting one or more acoustic force pulses to the cellular bodies provided on the wall surface based on generating one or more acoustic field gradients in the holding space
Implementation Method 2
determining the size of the cellular bodies and tracking locations of the cellular bodies during each of the one or more acoustic force pulses and after each of the one or more acoustic force pulses
Data Source
Figure 1~2A
Figure 2B
Figure 3~3(E)
AI summary
Methods and systems for determining cell properties are described, wherein a method may comprise the steps of receiving images representing manipulating cellular bodies in a holding space, the holding space comprising a wall surface, the manipulating including exerting one or more force pulses to the cellular bodies provided on the wall surface, the force pulses having a direction away from the wall surface; analyzing the images, the analyzing including determining the size of the cellular bodies and tracking locations of the cellular bodies during each of the one or more force pulses and after each of the one or more force pulses, the tracking locations defining one or more first trajectories of the cellular bodies moving away from the wall surface and one or more trajectories of the cellular bodies moving towards the wall surface; determining densities of the cellular bodies based on the one or more second trajectories and a sedimentation model of the cellular bodies moving towards the wall surface and determining cellular body velocities based the one or more first trajectories and a velocity model of the cellular bodies moving away from the wall surface; and, determining a contrast factor for each of the cellular bodies based on the sizes and the densities of the cellular bodies, the force applied to the cellular bodies and the cellular body velocities and determining a compressibility for each of the cellular bodies based on the determined contrast factors.