Electrode Array Cell Sampling for Controlled RNA Capture
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Solution Overview
Problem
Existing methods for 2D RNA sequencing produce libraries of variable quality and complexity due to inefficient RNA migration and lack of control over RNA release from individual cells, leading to inaccurate representation and degradation of rare RNA species.
Innovation Solution
A system and method using an electrode array with controlled electrical lysis and electrophoresis to actively capture nucleic acids, allowing precise control over RNA release and capture, utilizing a chip with a unique primer array and control circuit for real-time assessment of capture efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If RNA is released from cells using conventional methods, then RNA can be captured for sequencing, but the RNA migration is inefficient and lacks control, leading to variable library quality
Solution Approach 1:
The patent replaces conventional mechanical or chemical lysis methods with electrical lysis using electrodes. Electrical lysis provides precise control over RNA release from individual cells, improving both the reliability of library quality and the productivity of RNA capture yield by enabling controlled electrophoresis of released RNA to specific locations.
Solution Approach 2:
The patent changes the physical state and movement control of RNA from passive diffusion to active electrophoresis by applying electrical parameters. This allows controlled migration of RNA molecules to specific capture locations, resolving the contradiction between reliable capture and efficient productivity.
2Measurement precision
If RNA is released without controlled lysis, then cells can be processed, but lateral migration occurs and rare RNA species are degraded
Solution Approach 1:
The patent segments the tissue section into individual cells or small groups, applying electrical lysis and electrophoresis at the single-cell level. This segmentation prevents lateral migration between cells and preserves rare RNA species by isolating their transcripts for targeted capture, thereby improving measurement precision and reducing substance loss.
Solution Approach 2:
The patent introduces an intermediary electrophoresis field as a mediator between cell lysis and RNA capture. This intermediary controlled electrical field guides RNA molecules directly to capture locations, preventing lateral migration and protecting rare RNA species from degradation while maintaining transcriptome profile accuracy.
3Ease of operation
If conventional RNA release methods are used, then processing is simple, but control over individual cell RNA release is lacking
Solution Approach 1:
The patent replaces complex multi-step mechanical and chemical lysis protocols with a single electrical lysis step using applied voltage. This substitution maintains ease of operation while dramatically improving manufacturing precision through controlled electrical parameters that enable individual cell RNA release without requiring multiple processing stages.
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
Enhances RNA capture yield and reduces lateral migration, providing a more accurate 2D transcriptome profile by ensuring precise RNA collection and library quality assessment before sequencing.
Implementation Method 1
A control circuit may be configured to apply an individually controllable voltage to each sampling electrode of the electrode array and measure an electrical property of the sampling electrode. In some examples, the control circuit may be configured to apply a lysis voltage to the sampling electrode... An electrophoresis voltage may be applied to the sampling electrode, if the lysis voltage was applied to the sampling electrode, to drive nucleic acids
Implementation Method 2
A control circuit may be configured to apply an individually controllable voltage to each sampling electrode of the electrode array and measure an electrical property of the sampling electrode. In some examples, the control circuit may be configured to measure a current for the sampling electrode
Data Source
AI summary
Methods, systems, and devices for sampling/isolating material from cells. An exemplary system may comprise a chip including an electrode array of sampling electrodes arranged along a surface of the chip. A cell-receiving area may be located adjacent the surface of the chip. The system also may comprise a tag array of tags supported by the chip and aligned with the electrode array. Each tag of the tag array may include an identifier that is unique to the tag within the tag array. Each tag may be configured to bind nucleic acids, or a capturing agent distinct from the tag may be aligned with each sampling electrode of the electrode array to capture a protein or other analyte of interest. The system further may comprise a control circuit configured to apply an individually controllable voltage to each sampling electrode of the electrode array and measure an electrical property of the sampling electrode.