Microelectrode Array for Deterministic Cell Electroporation
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Solution Overview
Problem
Existing methods for manipulating and electroporating single cells are inefficient and non-deterministic, often resulting in sub-optimal electroporation due to varying electric field intensities and cell positioning, leading to cell death or insufficient permeabilization.
Innovation Solution
The use of non-uniform, time-varying force fields characterized by stable points of equilibrium, such as negative or positive dielectrophoresis, electrophoresis, or electro-hydrodynamic motions, combined with integrated optical sensors, allows for deterministic control and selective electroporation of cells using an array of microelectrodes to create controlled permeabilization of cell membranes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to manipulate and electroporate single cells, then cell processing can be performed, but the electroporation efficiency is sub-optimal and cell positioning is non-deterministic
Solution Approach 1:
The system divides the electrode array into individually controllable elements, allowing separate manipulation of each cell position. This segmentation enables precise control over which cells receive electroporation treatment, improving both positioning precision and electroporation reliability.
Solution Approach 2:
Different regions of the electrode array are applied with different voltage patterns to create localized force fields. This allows specific zones to attract and hold cells at predetermined positions while other zones remain active for electroporation, achieving both precise positioning and reliable electroporation treatment.
2Ease of operation
If varying electric field intensities are applied during cell manipulation, then cell movement can be achieved, but cell viability decreases due to insufficient or excessive field strength
Solution Approach 1:
The system dynamically adjusts voltage patterns applied to different electrode regions based on real-time cell positioning and electroporation needs. This dynamic control allows the electric field intensity to be optimized for each specific cell, preventing both insufficient manipulation and excessive field strength that would cause cell death.
Solution Approach 2:
The system employs periodic voltage application with different patterns for different phases: first for cell attraction and positioning, then for electroporation. This periodic action allows the cell to experience appropriate field strengths for manipulation without sustained exposure to damaging intensities, maintaining cell viability while achieving effective electroporation.
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 enables effective and selective transformation of cells, including the introduction of exogenous genetic material, accurate purification, and rapid isolation of cells, while maintaining cell viability by optimizing electroporation conditions.
Implementation Method 1
a non uniform, time varying force fields... The force used for trapping in suspension particles in a fluid medium is the negative dielectrophoresis
Implementation Method 2
The force used for trapping in suspension particles in a fluid medium is the negative dielectrophoresis... AC electroosmosis... PCT WO 2004/071668 A1 discloses an apparatus for concentrating particles on some electrodes, by exploiting the so-called electro-hydrodynamic flows
Implementation Method 3
within the micro-chamber/s at least a force field (F) acting on the particles is activated, in order to cause a displacement of the particles only in a pre-fixed direction
Data Source
Figure 1(a)~3(b)
Figure 4~5b
AI summary
Method for the selection or the processing of first particles sensitive to the application of an external stimulus including the step of producing, through the application of the external stimulus, the permeabilization of at least a selected first particle, consisting in the organization of the first particles (CELL) through a first force field (FMAN), to generate a second force field (FZAP) substantially placed in proximity of at least a selected first particle to be permeabilized.