Multistage Microfluidic Device for Intracellular Delivery
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Solution Overview
Problem
Existing microfluidic systems for intracellular delivery face challenges in achieving high efficiency and maintaining cell viability due to their specificity to cargo size or cell properties, leading to decreased efficiency, throughput, and viability issues across different cell types.
Innovation Solution
A microfluidic device with constrictions of varying cross-sections applies both hydrodynamic and contact-based compression forces to cells, allowing for progressive deformation and enhanced pore creation in the cell membrane, enabling efficient delivery of cargo molecules regardless of cell elasticity and size.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional microfluidic systems use single-constriction design for intracellular delivery, then the device structure is simple, but delivery efficiency is low and cell viability decreases
Solution Approach 1:
The microfluidic channel is segmented into multiple constrictions with progressively decreasing cross-sectional areas. This segmentation allows cells to undergo staged deformation - first experiencing hydrodynamic forces in larger constrictions, then contact-based compression in smaller constrictions - achieving high delivery efficiency while maintaining cell viability through controlled progressive mechanoporation
Solution Approach 2:
Different regions of the microfluidic channel are designed with locally optimized properties: upstream constrictions have larger cross-sections to apply gentle hydrodynamic forces, while downstream constrictions have smaller cross-sections for stronger contact-based compression. This local quality variation enables differentiated force application along the flow path, optimizing both delivery efficiency and cell survival
2Reliability
If microfluidic systems apply high shear stress for short duration, then cell membrane permeabilization is achieved, but loading efficiency is low
Solution Approach 1:
Cells are pre-deformed by hydrodynamic forces in larger upstream constrictions before entering smaller downstream constrictions. This preliminary action prepares the cell membrane for subsequent compression, creating optimal conditions for cargo loading while maintaining high membrane permeabilization efficiency
Solution Approach 2:
The multi-constriction design enables continuous useful action by maintaining cell deformation throughout the entire flow path. Cells experience sustained mechanoporation effects across multiple constrictions rather than a single brief event, continuously enhancing cargo loading efficiency while preserving membrane permeability
3Productivity
If contact-based compression is applied through narrow constrictions, then delivery efficiency increases, but cell viability decreases significantly
Solution Approach 1:
Larger upstream constrictions provide a cushioning effect by applying gradual hydrodynamic forces that prepare cells for the stronger compression in downstream constrictions. This beforehand cushioning reduces mechanical shock to cells, maintaining viability while enabling efficient cargo delivery through the narrower downstream constrictions
4Productivity
If microfluidic devices are designed for high throughput, then processing speed increases, but delivery efficiency and cell viability are compromised
Solution Approach 1:
The multi-constriction microfluidic device achieves universality by simultaneously optimizing for high throughput, high delivery efficiency, and high cell viability. The staged constriction design allows the single device to perform multiple functions: rapid cell processing through parallel flow paths, precise cargo delivery through optimized deformation zones, and cell survival protection through gradual mechanoporation
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 achieves high delivery efficiency for both small and large cargo molecules across various cell types without compromising cell viability, improving upon previous methods by using iterative cell deformation and controlled force application.
Implementation Method 1
one of said constrictions has a cross-section that is larger than the average cross-section of said cell and adapted to apply hydrodynamic forces to said cell
Implementation Method 2
a second of said constrictions has a cross-section that is equal to or smaller than the average cross-section of said cell and adapted to apply contact-based compression forces to said cell
Implementation Method 3
Mechanoporation i.e. mechanical manipulation relies on mechanical forces to deform cells in suspension allowing for transient plasma membrane permeabilization
Data Source
AI summary
The present invention relates to a microfluidic device for introducing pores into and/or enhancing the diameter of pores in the cell membrane of a cell by cell deformation for delivery of cargo molecules into said cell, the device comprising: an inlet and an outlet; and at least one microfluidic channel positioned between said inlet and said outlet, defining a lumen, adapted to allow a cell and cargo molecules in a suspension solution to pass therethrough; wherein the at least one microfluidic channel comprises at least two constrictions with different cross-sections, wherein one of said constrictions has a cross-section that is larger than the average cross-section of said cell and adapted to apply hydrodynamic forces to said cell and a second of said constrictions has a cross-section that is equal to or smaller than the average cross-section of said cell and adapted to apply contact-based compression forces to said cell, while allowing said cell to pass through said constrictions.