Droplet Trapping Site for Co-encapsulation
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Solution Overview
Problem
Conventional droplet-based microfluidic systems face low co-encapsulation efficiency of distinct particles due to Poisson statistics, leading to high sample loss and reduced throughput in biological assays, especially when requiring one-to-one pairing of cells or particles.
Innovation Solution
A system comprising a substrate with trapping sites that capture and merge droplets of different sizes, ensuring each site traps one larger and one smaller droplet, allowing for precise pairing and merging of droplets containing desired components like cells or barcoded beads, using demulsifiers or electrical pulses for merging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional co-flowing scheme is used for droplet encapsulation, then the process is simple to implement, but the co-encapsulation efficiency is low due to Poisson statistics
Solution Approach 1:
The system performs preliminary sorting of droplets containing target particles before encapsulation. By pre-separating and concentrating target particles into individual droplets, the system ensures that subsequent co-encapsulation events involve only droplets with desired components, thereby achieving high co-encapsulation efficiency while maintaining operational simplicity
Solution Approach 2:
The patent introduces an intermediary sorting mechanism between droplet generation and co-encapsulation. This intermediary step uses sorting devices to act as a mediator that selects and prepares droplets with target particles, enabling efficient one-to-one pairing without requiring complex simultaneous multi-particle encapsulation
2Manufacturing precision
If low concentration cell suspension is used to avoid multiple cells per droplet, then single-cell occupancy is improved, but the pairing efficiency of distinct particles is reduced
Solution Approach 1:
The system performs preliminary concentration of target particles into individual droplets at low concentration, then sorts and selects droplets containing target particles. This preliminary action allows the system to maintain low concentration for accurate single-cell occupancy while subsequently achieving high pairing efficiency through selective sorting and merging of pre-prepared droplets
Solution Approach 2:
The patent segments the encapsulation process into distinct stages: (1) generation of droplets at low concentration for accurate single-cell occupancy, (2) sorting of droplets containing target particles, and (3) merging of sorted droplets. This segmentation allows each stage to optimize for its specific goal without compromising the others
3Measurement precision
If active sorting is used to enrich positive droplets, then the precision of particle pairing is improved, but the system complexity increases
Solution Approach 1:
The patent introduces an intermediary sorting device that acts as a mediator between simple droplet generation and the final co-encapsulation process. This intermediary component provides the necessary sorting functionality with minimal added complexity, enabling accurate particle pairing while maintaining overall system simplicity through modular design
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 significantly increases the co-encapsulation efficiency of desired particles, reducing sample loss and improving assay throughput by ensuring precise one-to-one pairing within droplets, overcoming the limitations of Poisson statistics.
Implementation Method 1
trapping sites... configured to trap one or more droplets floating in a flow channel
Implementation Method 2
collected larger and smaller droplets are merged (e.g., via a demulsifier or electricity)
Implementation Method 3
collected larger and smaller droplets are merged (e.g., via a demulsifier or electricity)
Data Source
AI summary
Provided herein are systems, methods, and articles of manufacture for collecting and merging two different size droplets using a substrate comprising a plurality of trapping sites. In certain embodiments, provided herein are systems composed of a plurality of larger droplets and smaller droplets and a substrate comprising a plurality of trapping sites where each trapping site is configured to trap only one of the larger droplets and only one of the smaller droplets when the larger droplet is already present at the trapping site. In particular embodiments, the larger and/or smaller droplets are sorted prior to being contacted with the substrate to ensure they contain the desired component (e.g., cell or barcoded bead). In other embodiments, each trapping site is composed of one or multiple fluidically linked capture wells. In some embodiments, collected larger and smaller droplets are merged (e.g., via a demulsifier or electricity).