Electrical Cell-Trapping Array for Single-Cell Nucleic Acid Sequencing
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Solution Overview
Problem
Current methods for high-throughput sequencing of nucleic acids at the single-cell level are not cost-effective and efficient in characterizing individual cells and identifying nucleic acids.
Innovation Solution
A method involving a solid surface with an array of identical features, where each feature has a library of oligonucleotides with unique molecular identifiers and sequences complementary to nucleic acids of interest, using an electric field to immobilize cells, release and hybridize nucleic acids, and sequence them for identification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If droplet microfluidic platforms are used for high throughput sequencing of nucleic acids with single-cell resolution, then sequencing throughput is improved, but cost and operational efficiency deteriorate
Solution Approach 1:
The device segments the sample processing into distinct functional zones: a loading zone for cell introduction, multiple trapping arrays for parallel cell capture, and sequencing zones for nucleic acid analysis. This segmentation enables high-throughput processing while using simpler, lower-cost components in each zone rather than requiring complex integrated microfluidic systems.
Solution Approach 2:
The electrode array serves multiple functions: it traps cells via dielectrophoresis, releases cells through controlled electric field application, and facilitates nucleic acid extraction. This multi-functionality reduces the need for separate specialized components, lowering overall system cost while maintaining high throughput capability.
2Productivity
If droplet microfluidic platforms are used for high throughput sequencing of nucleic acids with single-cell resolution, then sequencing throughput is improved, but operational efficiency deteriorates
Solution Approach 1:
The device enables self-service operation through automated cell trapping and processing. The dielectrophoretic trapping automatically concentrates and holds cells in designated positions without manual intervention, and the electric field-controlled release automatically transfers cells to sequencing zones, reducing operational complexity while maintaining high throughput.
Solution Approach 2:
Cells are pre-trapped and positioned in the trapping arrays before sequencing begins. This preliminary action organizes the sample in advance, allowing subsequent sequencing operations to proceed efficiently without manual sample preparation during the sequencing process itself.
3Manufacturing precision
If electrode arrays are used for deposition of DNA oligonucleotides of defined sequence and position, then positioning precision is improved, but device complexity increases
Solution Approach 1:
The patent combines oligonucleotide deposition and cell trapping functions into a single electrode array system. The same electrodes that generate dielectrophoretic fields for cell manipulation also serve as the substrate for oligonucleotide attachment, eliminating the need for separate precision deposition equipment and reducing overall device complexity while maintaining positioning accuracy.
4Reliability
If cell capture arrays using dielectrophoresis are used for detection of circulating tumor cells, then cell capture efficiency is improved, but versatility for nucleic acid characterization deteriorates
Solution Approach 1:
The electrode array is designed as a universal platform that performs both cell capture via dielectrophoresis and subsequent nucleic acid characterization. After cells are trapped, the same device can release cells, extract nucleic acids, and perform sequencing, providing versatile single-cell analysis capability while maintaining high capture efficiency.
Solution Approach 2:
The device dynamically transitions between different operational modes: cell trapping mode, cell release mode, and nucleic acid sequencing mode. The electric field parameters are dynamically adjusted to enable each function, allowing a single device to perform multiple functions that would otherwise require separate specialized systems.
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, low-cost, high-capture efficiency for identifying nucleic acid sequences of single cells, allowing for analysis of all or part of the transcriptome, genome, or exome with single-cell resolution.
Implementation Method 1
immobilizing single cells at the identical features on the array on the solid surface by application of an electric field
Data Source
AI summary
Provided herein are methods, systems, kits and compositions for identifying nucleic acids of interest from individual cells. The methods include isolating single cells on electrodes and identifying nucleic acids of interest from the isolated cells by sequencing.