Nanoelectronic Mesh for Single-Cell Electrophysiology and Transcriptomics
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Solution Overview
Problem
Current methods for probing cellular electrophysiological and transcriptional states in 3D tissues face limitations in throughput, accessibility, and longevity, particularly in integrating data at single-cell resolution and tracing long-term activities across tissues.
Innovation Solution
The development of 'tissue-like' electronics with nanoelectronic sensing units embedded in a flexible mesh network for seamless integration with 3D tissues, combined with in situ single-cell RNA sequencing techniques like STARmap, enables continuous profiling of multimodal physiological activity and gene expression at high resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Patch-seq approach is used to probe cellular transient electrical states and transcriptional states, then single-cell resolution is achieved, but throughput is limited
Solution Approach 1:
The tissue is divided into multiple regions with embedded nanoelectronic sensors, each capable of independent recording. This segmentation allows parallel processing of multiple cells simultaneously, increasing throughput while maintaining single-cell resolution through individual sensor identification via electronic barcodes.
Solution Approach 2:
The patent replaces mechanical patch-clamp techniques with nanoelectronic sensors embedded in the tissue. These sensors continuously monitor electrophysiological activity without requiring mechanical intervention, enabling high-throughput, long-term recording while maintaining single-cell resolution through spatial mapping and electronic barcodes.
2Productivity
If optical mapping combined with scRNAseq is used, then high throughput interrogation is achieved, but integration at single-cell resolution cannot be integrated
Solution Approach 1:
The patent merges nanoelectronic sensing with optical imaging by embedding fluorescently-labeled nanoelectronic units within the tissue. This combination allows simultaneous electrical recording and optical visualization, enabling high-throughput interrogation while maintaining single-cell resolution through the unique barcode identification system that links both modalities to specific cells.
Solution Approach 2:
Fluorescent barcodes are embedded with nanoelectronic sensors, allowing optical detection and identification of specific sensors and their associated cells. This color-based coding system enables high-throughput multiplexed recording while maintaining precise single-cell resolution through unique fluorescent signatures for each sensor-cell unit.
3Duration of action of moving object
If long-term tracing of single-cell activities is performed, then developmental processes can be studied, but accessibility and longevity in 3D tissue are challenging
Solution Approach 1:
Nanoelectronic sensors are embedded within the 3D tissue matrix, nesting the recording apparatus inside the biological structure. This integration allows long-term tracing of single-cell activities throughout the tissue volume while maintaining accessibility through the flexible mesh design that can be introduced and maintained within the tissue without disrupting its 3D architecture.
Solution Approach 2:
The nanoelectronic sensors are integrated into a flexible mesh structure that can be embedded within 3D tissue. This flexible architecture maintains tissue accessibility and structural integrity while enabling long-term recording, as the flexible mesh can accommodate tissue growth and deformation without compromising sensor access or signal quality.
Data Source
AI summary
Disclosed herein are methods and systems for correlating continuous physiological processes (e.g., electrophysiological activity) and biomolecular processes (e.g., gene expression) in cells within a tissue. Also disclosed herein are methods for preparing a tissue for continuous electrophysiological recording. Further disclosed herein are systems comprising nanoelectronic devices within cells in a tissue, wherein each nanoelectronic device comprises a unique electronic barcode. The methods and systems described herein comprise any tissue with electrical activity (e.g., brain tissue, heart tissue, nervous system tissue, muscle tissue, pancreas tissue, or gastrointestinal tract tissue). Additionally disclosed herein are methods for disease modeling, methods for discovering a target for treating a disease, and methods for drug screening.