Digital Microfluidic Cell Trapping for On-Demand Droplet Sorting
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Solution Overview
Problem
Current methods for selecting and sorting edited cells are laborious, time-consuming, and difficult to standardize, leading to non-reproducible results, especially when dealing with phenotypically silent gene edits and low cell density cultures.
Innovation Solution
A microfluidic device with a layered structure and electrode configuration for on-demand droplet creation, mixing, incubation, and sorting, allowing for precise trapping and manipulation of cells and droplets using dielectrophoresis and electrowetting principles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional sorting methods (FACS, resistance screens) are used to select and sort edited cells, then high-purity single cells can be obtained, but cell viability after sorting is low to moderate and the process is laborious and time-consuming
Solution Approach 1:
The system segments the cell sorting process into discrete droplet-based operations, where individual cells are encapsulated in separate droplets and manipulated independently through digital microfluidic control, enabling high-purity sorting without the mechanical stress of traditional FACS methods
Solution Approach 2:
The patent replaces mechanical sorting mechanisms (flow cytometry, magnetic sorting) with electric field-based digital microfluidic manipulation, using electrowetting and dielectrophoresis to control droplet movement and cell positioning, thereby improving cell viability while maintaining sorting precision
2Manufacturing precision
If traditional sorting methods are used, then cell isolation can be achieved, but the process is difficult to standardize and integrate, resulting in non-reproducible results
Solution Approach 1:
The patent merges multiple sorting operations into a single integrated microfluidic device platform, combining cell encapsulation, droplet manipulation, and sorting functions in one system, which standardizes the process and improves reproducibility across experiments
Solution Approach 2:
The digital microfluidic platform provides universal control over droplet operations through programmable electrode patterns, allowing the same device to perform multiple sorting functions (isolation, enrichment, purification) with consistent results, eliminating the need for multiple specialized devices
3Manufacturing precision
If limited dilution is used to find right clones, then single cells can be obtained, but the technique relies heavily on chance and probability resulting in low purity single cells
Solution Approach 1:
The system performs preliminary cell encapsulation in droplets before sorting, allowing cells to be pre-positioned and isolated in individual compartments, which eliminates the need for probabilistic dilution methods and ensures high-purity clone isolation through deterministic droplet manipulation
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
Enables efficient, reproducible, and high-purity sorting of edited cells with improved viability, facilitating standardized and automated processes for isolating isogenic populations.
Implementation Method 1
directly coupled to a serpentine channel with traps. The device can perform on-demand operations on droplets in channels. These on-demand operations include for example on-demand droplet generation through a T-junction droplet generator, merging droplets, trapping of droplets, selectively releasing or keeping droplets on device and merging droplets
Implementation Method 2
A microfluidic device with a layered structure and electrode configuration for on-demand droplet creation, mixing, incubation, and sorting, allowing for precise trapping and manipulation of cells and droplets using dielectrophoresis and electrowetting principles
Data Source
AI summary
Microfluidic devices, systems and methods are described herein. The devices, systems and methods provide for trapping particles, including cells. Methods of generating a droplet in a microfluidic device and collecting droplets from microfluidic devices are also disclosed herein.