Flow-Through Electroporation for Automated Cell Editing
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Solution Overview
Problem
Current methods for genome editing with engineered nucleases are not compatible with automation due to low efficiencies and challenges with cell transformation, growth measurement, and cell selection, limiting the complexity and nature of cell populations that can be created.
Innovation Solution
The development of automated multi-module cell editing instruments and systems that utilize flow-through electroporation (FTEP) devices for introducing nucleic acids into cells, enabling recursive genome editing and the creation of libraries of living cells with desired genomic changes through nuclease-directed techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Extent of automation
If traditional benchtop devices are used for cell transformation, then manual operation is possible, but automation compatibility is poor and efficiency is low
Solution Approach 1:
The patent replaces manual mechanical cell transformation methods with an automated flow-through electroporation device that uses electrical fields to introduce nucleic acids into cells. The device features automated fluid handling, electrical pulse delivery, and cell processing, eliminating manual intervention while achieving high transformation efficiencies of 10^-2 to 10^0 transformations per cell
Solution Approach 2:
The invention changes the physical parameters of cell transformation by using controlled electrical pulses (electroporation) instead of traditional mechanical methods. The device applies specific voltage pulses (e.g., 10-500 V/cm) for defined durations (microseconds to milliseconds) to create temporary membrane permeability, enabling efficient nucleic acid uptake while being fully automatable
2Productivity
If manual cell processing methods are used, then flexibility is maintained, but transformation efficiency and scalability are limited
Solution Approach 1:
The patent merges multiple functions (cell suspension, nucleic acid delivery, electroporation, and cell recovery) into a single integrated flow-through device. The device combines fluidic channels, electrodes, and processing chambers in one unit, achieving high transformation efficiency while maintaining manageable complexity through functional integration
Solution Approach 2:
The flow-through electroporation device is designed to handle multiple cell types and nucleic acid preparations universally. It can process bacteria, yeast, and mammalian cells using the same basic platform, adjusting only electrical parameters and flow rates, thereby achieving high productivity without proportionally increasing device complexity
3Adaptability or versatility
If recursive genome editing is implemented, then complexity of cell populations increases, but automation compatibility decreases
Solution Approach 1:
The device enables continuous recursive genome editing by maintaining automated flow-through processing through multiple editing cycles. Cells can be subjected to sequential electroporation events with different nucleic acid preparations without manual intervention, allowing complex multi-step genome editing while preserving full automation compatibility
Solution Approach 2:
The system performs preliminary preparation of multiple nucleic acid constructs before cell processing, storing them in automated dispensing units. This allows recursive editing to be pre-programmed and executed automatically through multiple flow-through cycles, increasing cell population complexity while maintaining automation
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
These systems achieve high efficiency in cell transformation, allowing for the generation of large libraries of edited cells with precise genomic edits, improving the scalability and complexity of cell populations that can be created, and enabling further experimentation outside of the automated instrument.
Implementation Method 1
a flow-through electroporation (FTEP) device for introducing an exogenous material into cells in a fluid
Data Source
AI summary
In an illustrative embodiment, automated multi-module cell editing instruments comprising one or more flow-through electroporation devices or modules are provided to automate genome editing in live cells.