Dielectrophoretic Microwell Assay for Cell-Cell Interaction Sequencing
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Solution Overview
Problem
Existing technologies lack the ability to efficiently link genetic information of single cells with their phenotypic information, such as specific functional features, in a high-throughput manner, particularly in the context of cell-cell interactions.
Innovation Solution
A microfluidic device with a substrate featuring a microwell array and electrodes, where each microwell is coated with barcode molecules, allowing for the trapping and sequencing of individual cells to determine their interactions, utilizing a system with a flow channel for fluid communication and barcode-based nucleic acid sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If single cell sequencing is performed to obtain genetic information, then genetic information can be analyzed, but phenotypic information and functional features cannot be linked efficiently
Solution Approach 1:
The system segments cells into individual microwells, with each microwell containing a single cell and its associated barcode molecules. This segmentation enables independent analysis of each cell's genetic and phenotypic information while maintaining the ability to process many cells in parallel across the microwell array, thus resolving the contradiction between information linkage and high-throughput capability
Solution Approach 2:
Barcode molecules are pre-coated onto microwell surfaces before cell introduction. Each barcode contains both genetic identifiers and phenotypic feature information. When cells are trapped in microwells, they automatically associate with these pre-prepared barcodes, establishing the linkage between genetic and phenotypic information in advance of sequencing, enabling high-throughput analysis without losing information
2Measurement precision
If microwell array with barcode molecules is used, then cell trapping and identification can be achieved, but device complexity increases
Solution Approach 1:
The microwell array serves multiple functions simultaneously: it acts as a trapping structure for single cells, a platform for barcode molecule attachment, a sorting mechanism based on barcode sequences, and a reaction chamber for nucleic acid extraction. This multi-functionality reduces the need for separate devices for each operation, thereby managing device complexity while maintaining high measurement precision
Solution Approach 2:
Barcode molecules serve as intermediaries between the physical microwell structure and the cellular information. The barcodes are coated on microwells and mediate the association between cells and their genetic/phenotypic identifiers. This intermediary approach simplifies the device design by using molecular tags rather than complex mechanical identification systems, maintaining precision without excessive complexity
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 high-throughput analysis of cell-cell interactions by correlating genetic and phenotypic information, facilitating the identification of cells with specific functionalities for therapeutic applications.
Implementation Method 1
A space between the first signal electrode and the ground electrode in the microwell can be capable of trapping a first cell when a first signal is applied to the first signal electrode and the ground electrode. A space between the second signal electrode and the ground electrode in a microwell of the plurality of microwells can be capable of trapping a second cell when a second signal is applied to the second signal electrode and the ground electrode.
Data Source
AI summary
Disclosed herein include methods, devices, kits, and systems for nucleic acid sequencing, for example, to determine cell-cell interaction using a dielectrophoresis microfluidic device.