Microfluidic Cell Deformation Using Viscoelastic Flow Focusing
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Solution Overview
Problem
Existing methods for studying cell deformations, such as atomic force microscopy and microfluidics-based approaches, suffer from low throughput and require contact with probes, leading to contamination and complex operation procedures.
Innovation Solution
A method utilizing a non-Newtonian viscoelastic fluid to focus cells in a focusing microchannel without a sheath flow, followed by deformation in a deformation microchannel without wall contact, enabling high-throughput cell deformation analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single cell measurement techniques (AFM, micropipette aspiration) are used to achieve accurate deformability values, then measurement precision is improved, but throughput remains very low and operation procedures become tedious
Solution Approach 1:
The invention segments the cell analysis process into parallel microfluidic channels, where each channel independently processes cells. This allows simultaneous measurement of multiple cells (high throughput) while maintaining the precision of individual cell analysis through controlled deformation in each channel segment.
Solution Approach 2:
The invention uses hydrodynamic flow fields in microfluidic channels to deform cells, replacing mechanical probes (AFM cantilevers, micropipettes) with fluid forces. This contactless approach maintains measurement accuracy while enabling parallel processing of many cells simultaneously, dramatically increasing throughput.
2Measurement precision
If probe-based methods (AFM cantilever, electrodes, microporous filters) are used to measure cell deformability, then measurement precision is improved, but cell contamination occurs due to contact with probes
Solution Approach 1:
The invention replaces solid probes (AFM cantilevers, electrodes, filters) with hydrodynamic flow fields that deform cells contactlessly. The cells are suspended in fluid and deformed by controlled flow patterns, eliminating direct contact with probe surfaces and thus preventing contamination while maintaining measurement precision.
Solution Approach 2:
The invention introduces a fluid medium as an intermediary between the measurement system and cells. Instead of direct probe-cell contact, the fluid transmits deformation forces to cells through hydrodynamic fields, acting as a non-contaminating mediator that preserves cell integrity.
3Productivity
If constriction-based deformability cytometry (cDC) is used to achieve high throughput, then productivity is improved, but cells contact the constriction walls causing potential contamination and measurement artifacts
Solution Approach 1:
The invention uses extensional flow fields generated by counterpropagating liquid flows to stretch cells in the center of the channel. This hydrodynamic approach creates a contactless deformation zone where cells are stretched by fluid forces rather than mechanical constrictions, eliminating wall contact while maintaining high throughput through parallel channel processing.
Solution Approach 2:
The invention transitions from 2D constriction-based deformation (cDC) to 3D extensional flow deformation (xDC). By using counterpropagating flows that create extensional stress fields throughout the channel volume, cells deform in the flow direction without needing to pass through narrow constrictions, eliminating wall contact while enabling parallel processing.
4Object-affected harmful factors
If extensional flow deformability cytometry (xDC) with counterpropagating flows is used to achieve contactless deformation, then cell contamination is reduced, but device complexity increases due to multiple flow control requirements
Solution Approach 1:
The invention merges multiple flow control functions into a single integrated microfluidic device. The counterpropagating flows are generated within the same device using built-in flow generators, eliminating the need for separate external flow control systems and reducing overall device complexity while maintaining contactless deformation capability.
Solution Approach 2:
The invention designs a universal microfluidic platform that performs multiple functions: cell injection, flow generation, cell deformation, and imaging. This multi-functional integration reduces the number of separate components and control systems needed, simplifying the overall device architecture while enabling contactless extensional flow deformation.
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 high-throughput cell deformation analysis with improved biocompatibility and reduced contamination, facilitating applications like rare event detection and therapeutic interventions.
Implementation Method 1
the suspending medium is a non-Newtonian fluid having viscoelastic properties such that cells that enter the focusing microchannel are focused towards a center of the focusing microchannel due to the viscoelastic properties of the suspending medium
Implementation Method 2
causing cells that have exited the focusing microchannel to flow through a deformation microchannel arranged downstream of the focusing microchannel to cause deformation of cells in the flow, the deformation being caused by a flow pattern created by interaction of the flow with the walls of the deformation microchannel
Data Source
AI summary
In a method of investigating cell deformations, a sample fluid including cells suspended in a suspending medium is provided. A flow of the sample fluid through a focusing microchannel is established. The suspending medium is a non-Newtonian fluid having viscoelastic properties such that cells that enter the focusing microchannel are focused towards a center of the focusing microchannel due to the viscoelastic properties of the suspending medium, causing the cells to exit the focusing microchannel in single file. Subsequently, the sample fluid that has exited the focusing microchannel is caused to flow through a deformation microchannel arranged downstream of the focusing microchannel to cause a deformation of cells that have exited the focusing microchannel and have entered the deformation microchannel, the deformation being caused by a flow pattern created by interaction of the fluid flow with the deformation microchannel.