Microfluidic Cell Compression for Intracellular Delivery
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Solution Overview
Problem
Current methods for delivering small molecules, proteins, DNA, or RNA into cells are hindered by the difficulty of crossing the cellular membrane, and existing techniques are often inefficient, specific, and not suitable for clinically important cell types like stem cells and immune cells.
Innovation Solution
A microfluidic device with a flexible and rigid layer structure is used to compress cells, inducing temporary membrane perturbations for efficient uptake of agents, allowing for the delivery of a wide range of biological materials, including DNA-staining dyes, proteins, and nucleic acids, into various cell types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If chemical or electrical pulses are used to breach the membrane for intracellular delivery, then delivery efficiency is improved, but cell viability deteriorates
Solution Approach 1:
The invention changes the physical parameter of membrane permeability by applying controlled mechanical compression force through the microfluidic device. This mechanical compression temporarily increases membrane permeability to allow agent entry while avoiding the harmful effects of chemical or electrical methods, thus improving delivery efficiency while preserving cell viability.
2Productivity
If existing delivery methods are used, then delivery into some cell types is achieved, but adaptability to different cell types deteriorates
Solution Approach 1:
The microfluidic device is designed with a universal compression mechanism that can handle multiple cell types including stem cells and immune cells. The device applies mechanical compression force that is effective across different cell types without requiring method modification, thus achieving both delivery capability and adaptability to various cell types.
3Productivity
If mechanical compression is applied to induce membrane perturbation, then agent uptake is improved, but membrane integrity may deteriorate
Solution Approach 1:
The microfluidic device applies periodic or controlled mechanical compression to the cells as they pass through the flow channel. This controlled compression is sufficient to induce temporary membrane perturbations for agent uptake while being brief and localized, allowing membrane integrity to be maintained after the compression event.
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 method enables robust and precise intracellular delivery of agents, improving cell viability and efficiency, particularly for cell types previously difficult to target, with high throughput and versatility in handling different cell types and agents.
Implementation Method 1
pressurizing a control channel formed in the flexible layer of the microfluidic device such that the flexible layer physically compresses at least one of the first type of cell in the first flow fluid against the rigid layer
Implementation Method 2
causing a portion of the first agent to be taken up by the at least one of the first type of cell through the at least one temporary perturbation in the membrane
Data Source
AI summary
Described herein are methods inducing the uptake of an agent by a cell. Aspects of the invention relate to physically compressing the cell to induce perturbations (e.g., holes) in the cell membrane or wall. An agent is taken up by the cell through induced perturbations.