Adjustable Microfluidic Cell Traps for Real-Time Pair Interaction
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Solution Overview
Problem
Current microfluidic devices are unable to efficiently trap and analyze the naturally occurring physical interactions and behaviors of primary cells in a non-artificial environment, immobilize a high number of cell pairs without affecting viability, and separate cells after interaction, particularly for different-sized cells like lymphocytes and cancer cells, while also failing to study early signaling dynamics and correlate them to functional cellular events.
Innovation Solution
A microfluidic device with adjustable traps and actuators that accommodate different cell sizes, allowing real-time trapping, interaction analysis, and separation of cell pairs or triplets, featuring a unidirectional flow and actuators to adjust trap sizes and release cells without reversing flow, combined with sensors for real-time interaction data acquisition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If fixed-size trapping sites are used in microfluidic devices, then device structure is simple, but cells of different sizes cannot be efficiently paired
Solution Approach 1:
The patent implements adjustable trap sizes through actuators that can dynamically modify the trapping site dimensions to accommodate different cell sizes. This dynamic adjustment capability allows the device to adapt to various cell types (lymphocytes, cancer cells, etc.) without requiring multiple fixed-size traps, thus resolving the contradiction between adaptability and device complexity
Solution Approach 2:
The microfluidic device is designed with universal trapping sites that can be reconfigured for different cell types and interaction scenarios. The same trap structure serves multiple functions by adjusting its size parameters, enabling it to handle diverse cell pairing requirements (single-cell pairing, multi-cell interactions, different cell size ratios) within a single device platform
2Ease of operation
If flow reversal is used to release trapped cells, then cell release is achieved, but flow direction control becomes complex and time-consuming
Solution Approach 1:
The patent employs dynamic trap size adjustment through actuators to release cells, replacing the static flow reversal method. By dynamically modifying the trap dimensions to be larger than the cell size, cells are automatically released while maintaining unidirectional flow, thus simplifying flow control and improving ease of operation
Solution Approach 2:
The patent replaces the mechanical flow reversal system with an actuator-based trap size adjustment mechanism. This substitution eliminates the complexity of bidirectional flow control while achieving the same cell release function through dimensional modification of the trapping sites
3Quantity of substance
If bulk co-cultures are used to study cell interactions, then large number of cells can be analyzed, but single-cell heterogeneity is masked
Solution Approach 1:
The patent segments the bulk cell population into individual single-cell trapping sites within the microfluidic device. Each trap isolates specific cell pairs or small groups, enabling independent analysis of single-cell interactions while maintaining the ability to process large numbers of cells through parallel operation of multiple traps
Solution Approach 2:
The patent transitions from analyzing cells in a bulk three-dimensional suspension to organizing cells in a two-dimensional array of discrete microfluidic traps. This dimensional change enables simultaneous high-throughput processing while maintaining single-cell resolution, as each trap acts as an independent analysis compartment
4Ease of operation
If cells are trapped in fixed-size sites, then trapping is simple, but post-synapse cell isolation and separation is difficult
Solution Approach 1:
The patent uses dynamic trap size adjustment to facilitate post-synapse cell isolation. After interaction studies, the trap dimensions are modified to release cells individually or in controlled groups, enabling easy cell recovery for downstream applications such as single-cell omics or in vivo transfer while maintaining simple trap structure
Data Source
AI summary
The invention relates to a device for trapping at least one cell pair in a solution containing at least one first cell (C1) of a first type and at least one second cell (C2) of a second type, comprising: —a microfluidic channel (3) adapted for a unidirectional flow (F) of the solution; —a first trap (1) comprising a pair of first fingers (10a, 10b) arranged in the microfluidic channel (3), at least one of said first fingers (10a, 10b) being coupled to a respective first actuator (11a, 11b), said first actuator being configured to adjust the first trap (1) along a direction transversal to the flow (F) between an open position allowing passage of the first cell between the first fingers (10a, 10b) and a closed position adapted to a size of the first cell to allow trapping the first cell between the first fingers (10a, 10b); 15—a second trap (2) comprising a pair of second fingers (20a, 20b) arranged in the microfluidic channel (3), at least one of said second fingers (20a, 20b) being coupled to a respective second actuator (21a, 21b), said second actuator being configured to adjust the second trap (2) along a direction transversal to the flow (F) between an open position allowing passage of the second cell between the second fingers (20a, 20b) and a closed position adapted to a size of the second cell to allow trapping the second cell between the second fingers (20a, 20b); wherein the first trap (1) is arranged relative to the second trap (2) so as to form, when the first and second traps are in the closed position, a cell pair comprising the trapped first and second cells such that the second cell is in physical or chemical interaction with the first cell.