Optically-Mediated Electrowetting Microdroplet Merging
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Solution Overview
Problem
Existing microfluidic systems face challenges in culturing adherent cells, particularly in controlling the attachment and detachment of cells to microbeads, which is crucial for optimal growth and viability, and in efficiently handling adherent cells in a high-throughput environment, as they require precise control over the number of cells exposed to microbeads and suffer from reduced viability due to repeated transitions between adherent and suspension states.
Innovation Solution
A method and system using optically-mediated electrowetting (oEWOD) to manipulate microdroplets, allowing for the controlled merging and agitation of microdroplets containing microbeads and adherent cells, ensuring precise attachment of cells to microbeads, and enabling efficient handling and growth of adherent cells by maintaining them in their native adherent state throughout the process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional droplet platforms are used to combine solid microbeads with adherent cells, then high-throughput processing is enabled, but precise control over the number of beads each cell is exposed to cannot be achieved
Solution Approach 1:
The system divides the microbead population into separate compartments (microbead reservoirs) and the cell population into separate compartments (cell-containing droplets), then systematically combines them through controlled droplet merging operations. This segmentation allows independent control of bead and cell numbers, enabling precise control over the final bead-to-cell ratio while maintaining high-throughput processing capability.
Solution Approach 2:
The system performs preliminary sorting and grouping of microbeads into separate reservoirs based on size or other characteristics before the actual cell-bead combination step. This preliminary action enables precise control over the number of beads that will be exposed to each cell, as the bead composition is predetermined before droplet merging occurs.
2Adaptability or versatility
If adherent cells are taken between adherent and suspension states for recovery and expansion, then cell recovery for genetic analyses is enabled, but cell viability is reduced and expression profile changes
Solution Approach 1:
The system uses microbeads as an intermediary carrier that maintains cells in a stable adherent state throughout the recovery process. Instead of transitioning cells between adherent and suspension states, the microbeads serve as a portable substrate that allows cells to remain adherent while being transported and processed, thereby maintaining cell viability and expression profiles while enabling recovery for genetic analyses.
Solution Approach 2:
The system replaces the mechanical process of cell detachment and re-attachment with a passive transport mechanism where cells remain adherent to microbeads throughout the recovery process. This substitution eliminates the stresses associated with mechanical detachment and re-attachment, maintaining cell viability and preventing expression profile changes while still enabling cell recovery.
3Ease of manufacture
If fixed electrodes are used for actuation in lab-on-a-chip platforms, then mammalian cell culturing is enabled, but the number of cells that can be manipulated simultaneously is limited
Solution Approach 1:
The system divides the electrode structure into multiple independently controllable segments or zones, each capable of manipulating small groups of cells. This segmentation allows parallel manipulation of many cell groups simultaneously, greatly increasing productivity while maintaining the ability to perform mammalian cell culturing.
Solution Approach 2:
The system transitions from a single-layer fixed electrode configuration to a multi-dimensional electrode arrangement that can simultaneously actuate multiple cell groups in parallel. This dimensional expansion enables manipulation of a much larger total number of cells while maintaining control over each group, thus increasing productivity without compromising culturing capability.
4Ease of manufacture
If fixed electrode locations and sizes are used, then device fabrication is simplified, but flexibility and adaptability of the system is limited
Solution Approach 1:
The system employs dynamically reconfigurable electrode patterns that can be adjusted during operation to match different cell densities, assay requirements, and experimental designs. This dynamic adaptability allows the same fabricated device to serve multiple purposes and adapt to varying conditions, greatly enhancing versatility while maintaining fabrication simplicity through standardized electrode patterns that can be electronically reconfigured.
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 allows for efficient and scalable control of adherent cell attachment and detachment, promoting cellular attachment and proliferation, and maintaining high cell viability by avoiding the stresses associated with transitioning between adherent and suspension states, thus enabling controlled growth in a high-throughput environment.
Implementation Method 1
A method and system using optically-mediated electrowetting (oEWOD) to manipulate microdroplets
Implementation Method 2
agitating each of the merged microdroplets to cause the first and second fluids in each of the merged microdroplets to move
Data Source
AI summary
A method of handling an adherent cell in a microdroplet assaying system by conjugating an adherent cell to a microbead is provided. The method 50 comprises the steps of: loading a first plurality of microdroplets into a microfluidic space, wherein each of the first microdroplet 5 contains a microbead 52 and a first fluid; loading a second plurality of microdroplets into the microfluidic space, wherein each of the second microdroplet contains an adherent cell and a second fluid 54; merging the first plurality of microdroplets and the second plurality of microdroplets to form a plurality of merged microdroplets 56, each merged microdroplets containing the first and second fluids, at least one microbead and at least one adherent cell; and10 agitating each of the merged microdroplets 58 to cause the first and second fluids in each of the merged microdroplets to move such that at least one adherent cell adhere to the at least one microbead. [FIG. 1]15