Dielectrophoretic Microwell Barcoding 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, particularly in high-throughput single cell sequencing, and fail to correlate genetic information with specific functional features.
Innovation Solution
A microfluidic device with a microwell array and electrodes is used to trap and barcode cells, allowing for the sequencing of nucleic acids to determine cell-cell interactions, featuring a substrate with ground and signal electrodes and barcode molecules attached to microwells, enabling high-throughput analysis of cell functionality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high-throughput single cell sequencing is implemented, then the quantity of cells analyzed increases, but the ability to link genetic information with phenotypic information remains insufficient
Solution Approach 1:
The device segments cells into individual microwells, with each microwell containing a unique barcode that identifies the well's position. This segmentation allows simultaneous processing of many cells while maintaining individual cell identity and enabling linkage of genetic and phenotypic data through the barcode system.
Solution Approach 2:
The invention uses barcode copies (nucleic acid sequences) attached to each microwell to represent and track cell identity. These barcode copies are captured along with cellular material during lysis, creating a permanent link between the physical cell location and its genetic/phenotypic information that can be processed in parallel.
2Measurement precision
If single cell genetic information is analyzed individually, then measurement precision is improved, but productivity decreases
Solution Approach 1:
The invention merges individual cell analysis with high-throughput processing by combining multiple cells in a single microwell array, where each cell maintains individual barcode identification. This allows simultaneous sequencing of many cells while preserving single-cell resolution through the unique barcode assigned to each well.
Solution Approach 2:
The microwell array serves multiple functions: it physically contains individual cells, provides unique identification through barcodes, enables parallel processing, and facilitates both genetic and phenotypic analysis in a single platform, thereby achieving high throughput without sacrificing single-cell precision.
3Manufacturing precision
If cells are trapped using electrodes in microwells, then cell positioning precision is improved, but device complexity increases
Solution Approach 1:
The invention replaces complex mechanical positioning systems with an electrical field-based trapping mechanism. Electrodes generate dielectrophoretic forces that automatically position and hold cells in designated microwell locations, achieving precise cell positioning without complex mechanical actuators or moving parts.
Solution Approach 2:
The electrode system automatically positions cells into the correct microwells through dielectrophoretic trapping without requiring manual intervention or complex external positioning mechanisms. The system self-regulates cell placement based on the applied electrical fields and the physical structure of the microwell array.
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
Data Source
Figure 1A~1D
Figure 1E
Figure 2A~2B
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.