Lipid-Bilayer Microchannels for High-Throughput Cell Delivery
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Solution Overview
Problem
Current methods for intracellular delivery of biomolecules, such as gene-editing constructs, face challenges with fouling and clogging in microfluidic devices, limiting their scalability and reliability for clinical applications, particularly when processing large numbers of cells.
Innovation Solution
A microfluidic system with lipid bilayer-coated microchannels and constrictions that temporarily increase cell permeability, using lipid bicelles to form a conformal lipid bilayer on the channel surfaces, preventing fouling and enabling high-throughput delivery of molecules into cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If microfluidic channels are used for intracellular delivery, then delivery precision and control are improved, but fouling and clogging occur rapidly when processing large numbers of cells
Solution Approach 1:
The patent applies a lipid bilayer coating on the microchannel surfaces, which acts as a flexible thin film barrier. This lipid bilayer prevents direct interaction between cells and the microchannel surface, thereby reducing fouling and clogging while maintaining the precision of intracellular delivery through the controlled constriction geometry.
Solution Approach 2:
The lipid bilayer serves as an intermediary layer between the microchannel surface and the cells. This mediator prevents direct contact that would cause fouling, while still allowing the mechanical constriction to effectively permeabilize cells for biomolecule delivery, thus resolving the contradiction between precision and reliability.
2Productivity
If microfluidic channels process large numbers of cells rapidly, then productivity is improved, but fouling and clogging increase
Solution Approach 1:
The lipid bilayer coating on microchannel surfaces prevents fouling and clogging during high-throughput cell processing. By acting as a protective barrier, it enables sustained operation at high cell fluxes without the rapid degradation of device reliability that would otherwise occur.
Solution Approach 2:
The patent modifies the surface properties of the microchannel by coating with lipid bilayer, changing the physical-chemical parameters of the channel surface. This parameter change reduces cell adhesion and fouling, enabling high productivity while maintaining device reliability over extended operation periods.
3Productivity
If constriction is applied to increase cell permeability, then delivery efficiency is improved, but cell damage and fouling increase
Solution Approach 1:
The lipid bilayer coating on the microchannel constriction surface reduces direct mechanical stress and shear forces on cells during permeabilization. This protective layer allows efficient biomolecule delivery through the constriction while minimizing cell damage and membrane rupture that would otherwise occur.
Solution Approach 2:
The lipid bilayer acts as a mediator between the constriction geometry and the cell membrane. It facilitates the permeabilization process for efficient delivery while buffering the mechanical stresses, thereby reducing harmful effects on cell integrity and viability.
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 system effectively delivers biomolecules into large numbers of cells with high efficiency and viability, reducing clogging and extending device lifespan, capable of processing billions of cells in a clinically relevant timeframe.
Implementation Method 1
lipid bicelles to form a conformal lipid bilayer on the channel surfaces
Implementation Method 2
constrictions that are dimensioned to induce a transient increase in the permeability of cells that pass through the constrictions
Data Source
AI summary
A microfluidic device is disclosed that is used to process cells for the intracellular delivery of molecules or other cargo. The device includes one or more microchannels disposed in a substrate or chip and is fluidically coupled to an inlet configured to receive a solution containing the cells and the molecules or other cargo to be delivered intracellularly to the cells. Each of the one or more microchannels has one or more constriction regions formed therein, wherein the inner surface(s) of the microchannels and the one or more constriction regions have a lipid bilayer disposed thereon. In some embodiments, multiple microfluidic devices operating in parallel are used to process large numbers of cells. The device and method have particularly applicability to delivering gene-editing molecules intracellularly to cells.