Material Delivery to Red Blood Cells by Microfluidic Deformation
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Solution Overview
Problem
Conventional methods for delivering materials to anucleate cells, such as red blood cells, are ineffective due to their lack of repair mechanisms and endocytic pathways, leading to cell viability and function loss.
Innovation Solution
A microfluidics system with cell-deforming constrictions and controlled pressure application is used to perturb the cell membrane, allowing delivery of macromolecules without compromising cell viability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional techniques such as electroporation and lipofection are used to deliver materials to red blood cells, then material delivery can be achieved, but cell viability and function are severely compromised due to lack of repair mechanisms
Solution Approach 1:
The patent introduces a cell-permeable polymer as an intermediary carrier that facilitates material delivery through the cell membrane without directly damaging the cell. The polymer forms a complex with the material to be delivered, enables transmembrane transport, and then releases the material inside the cell, acting as a protective mediator throughout the process.
Solution Approach 2:
The patent changes the physical-chemical parameters of the delivery system by using polymers with specific properties (molecular weight, hydrophobicity, charge) that can dynamically interact with the cell membrane. The polymer's ability to change conformation and interaction strength based on local environment allows efficient delivery while maintaining cell integrity.
2Quantity of substance
If alternative methods using osmotic shock are used to deliver materials to red blood cells, then material can be delivered to the cytoplasm, but the red blood cells are killed or severely destabilized, reducing their half-life
Solution Approach 1:
The cell-permeable polymer serves as a gentle intermediary that avoids the extreme osmotic shock conditions. Instead of using harsh osmotic gradients that destabilize the membrane, the polymer-mediated delivery occurs under physiological conditions, preserving the cell's structural integrity and extended half-life.
3Duration of action of moving object
If red blood cells are modified to provide therapeutic functions, then longitudinal therapeutic benefits can be achieved, but the unique structural and physiological properties of RBCs make it difficult to deliver material into their cytoplasm
Solution Approach 1:
The cell-permeable polymer enables the red blood cell to self-deliver the therapeutic material without requiring complex external equipment or procedures. The polymer enters the cell autonomously and facilitates material transport using the cell's own membrane properties, making the modification process simple and scalable.
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 enables robust and scalable delivery of diverse materials to anucleate cells, preserving cell function and viability, suitable for therapeutic applications.
Implementation Method 1
the microfluidics channel comprises at least one cell-deforming constriction... high pressure... successful delivery of materials to RBCs was achieved
Implementation Method 2
cell-deforming constriction... rapid deformation based microfluidic system... causing perturbations in the cell membrane
Data Source
AI summary
The current subject matter includes methods, systems, articles, and techniques to deliver material to anucleate cells, such as red blood cells. Using a rapid deformation based microfluidic system, loading of red blood cells with macromolecules of different sizes has been shown. Although delivery to some mammalian cells, such as cancer cell lines and fibroblasts had been previously demonstrated using this technique, those designs were incompatible with RBCs that have dramatically different physical properties. Through the use of smaller constriction sizes, high speeds and different buffers successful delivery to red blood cells can be achieved. By enabling robust delivery to red blood cells in a simple, scalable manner, the current subject matter can be implemented in a diversity of applications that deliver material to study red blood cell diseases and/or use red blood cells as a therapeutic platform. Related apparatus, systems, techniques, and articles are also described.