Open Chamber Acoustic Device for Cell Binding Force Measurement
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Solution Overview
Problem
Current methods for profiling cell-matrix adhesion, such as atomic force microscopy and hydrodynamic-flow-based microfluidics, are limited in their ability to accurately measure cell detachment forces and kinetics for large populations of cells, particularly for rare cell events and heterogeneous cell subsets, and often require physical contact or induce variable shear forces.
Innovation Solution
An acoustic device with open chamber microfluidics that utilizes localized and uniform acoustic streaming to detach cells, allowing for precise control of forces and real-time imaging, enabling parallel profiling of cell-matrix adhesion at the single-cell level by adjusting pulsed acoustic power to apply forces ranging from hundreds of piconewtons to tens of nanonewtons.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If hydrodynamic-flow-based microfluidics or shear-spinning disks are used to measure large cell populations, then throughput is improved, but measurement precision and accurate force control deteriorate due to variable shear forces and lack of real-time imaging
Solution Approach 1:
The patent replaces hydrodynamic flow-based mechanical systems with an acoustic field-based system. Acoustic radiation pressure and acoustic streaming provide controlled forces on cells without the variable shear forces inherent in flow-based systems. This substitution enables both high throughput (measuring hundreds of cells) and high precision (accurate force measurement) simultaneously, resolving the contradiction between productivity and measurement precision.
Solution Approach 2:
The system incorporates real-time imaging feedback to monitor cell detachment events as acoustic power is increased. The imaging system provides continuous visual feedback on cell status, allowing precise determination of detachment forces. This feedback mechanism ensures measurement precision while maintaining high throughput through automated real-time monitoring of multiple cells.
2Measurement precision
If AFM or micropipette aspiration is used to achieve high measurement precision at single-cell level, then measurement precision is improved, but productivity deteriorates due to inability to measure large populations simultaneously
Solution Approach 1:
The patent segments the measurement system into multiple independent acoustic fields that can operate in parallel. Each acoustic field can independently measure cells, and multiple fields can function simultaneously to measure hundreds of cells in parallel. This segmentation maintains the single-cell measurement precision of AFM while achieving the high throughput previously only possible with bulk methods.
Solution Approach 2:
The acoustic device serves multiple functions: it can measure single cells with high precision, measure large populations in parallel, provide real-time imaging, and maintain cells in a physiological state without physical contact. This multi-functionality allows the system to achieve both high measurement precision and high productivity that were previously mutually exclusive.
3Quantity of substance
If closed chamber microfluidics is used to contain cells, then cell retention is improved, but device complexity and ease of operation worsen due to difficulty in accessing and manipulating cells
Solution Approach 1:
The patent uses a thin bottom surface of the chamber that is acoustically transparent, allowing acoustic fields to penetrate and interact with cells while maintaining chamber containment. This thin film structure enables both cell retention within the chamber and easy access for imaging and manipulation from below, resolving the contradiction between quantity retention and operational ease.
Solution Approach 2:
The acoustic field acts as an intermediary that can interact with cells through the chamber bottom without requiring physical access to the cells. This intermediary approach allows manipulation and measurement of cells while they remain contained in the chamber, maintaining both cell retention and ease of operation.
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 acoustic device achieves high-throughput, precise measurement of cell detachment forces and kinetics, suitable for various cell types, including cancer cells, with compatibility for real-time imaging and low sample consumption, overcoming limitations of existing technologies.
Implementation Method 1
one or more acoustic generators disposed in the plurality of open chambers, wherein the one or more acoustic generators are configured to create surface acoustic waves or bulk acoustic waves within the open chamber and produce a stream of the suspension liquid contained within the open chamber
Implementation Method 2
the Stokes drag force induced by the streaming ruptures the cell-matrix junction and detaches cells from the fibronectin-functionalized substrate
Data Source
AI summary
Disclosed is an apparatus, such as an acoustic for parallel profiling cell-matrix adhesion at single-cell level via the introduction of localized and uniform acoustic streaming into an open chamber microfluidic device. The adherent cells within the open chamber can be detached by the streaming-induced Stokes drag force, thereby allowing an accurate determination of the relevant forces and kinetics. The current device and method includes the digital regulation of acoustic streaming from a low level to high levels, and a large number of adherent cells can be ruptured from the substrate, and the particular adhesive forces and kinetics can be determined by the applied power. The acoustic device and the associated detachment technique can characterize the adhesion dynamics and kinetics of cells, such as mammalian cells and bacterial cells. And because fibronectin mimics cells and/or cell matrices, the acoustic device and the corresponding method has broad application in determining the force(s) required to detach cells from other types of cells and/or cell matrices.