Single-Cell Polyomics Analysis via Spatial Barcoding
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Solution Overview
Problem
Current technologies are unable to simultaneously sequence over 10,000 single cells, effectively handle low-input samples, and measure polyomics information to correlate gene expression with regulatory elements, limiting their use in clinical settings and understanding cellular heterogeneity.
Innovation Solution
A high-throughput single-cell polyomics analysis method using deterministic molecular barcodes in a spatially-defined array, allowing for the processing of tens of thousands of single cells by linking multiple 'omics' information to their spatial location, enabling the analysis of low cell number/quality samples and reducing sequencing costs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current sequencing technologies are used, then sequencing can be performed, but the throughput is limited to less than 10,000 single cells
Solution Approach 1:
The system divides the sequencing process into separate functional modules: cell capture in microwells, barcode assignment, and sequencing. Each microwell contains a unique barcode that segments the identification of individual cells, enabling parallel processing of thousands of cells simultaneously while maintaining single-cell resolution through the one-to-one mapping between microwells and barcodes.
Solution Approach 2:
The patent introduces a spatial dimension by assigning physical locations (microwell positions) to biological entities (cells). This spatial coding allows multiple cells to be processed in parallel across different locations while maintaining individual identification, thereby increasing throughput without sacrificing single-cell measurement precision.
2Quantity of substance
If traditional methods are used, then sequencing can be performed, but low-input samples with low cell numbers cannot be effectively handled
Solution Approach 1:
The system performs preliminary actions by pre-assigning unique barcodes to microwells before cell input. This allows the system to track and identify cells from the outset, even when starting with low cell numbers. The barcodes are prepared in advance and linked to spatial locations, enabling reliable detection and analysis of rare cells without requiring large input quantities.
3Adaptability or versatility
If multiple omics measurements are performed, then comprehensive molecular information can be obtained, but the complexity of the system increases
Solution Approach 1:
The microwell array system serves multiple functions simultaneously: cell capture, spatial coding, barcode assignment, and preparation for various omics measurements (transcriptomics, proteomics, epigenomics). The same physical platform and barcode system can be used for different types of molecular analyses, making the system universal and adaptable without requiring separate complex systems for each measurement type.
Solution Approach 2:
The molecular barcode acts as an intermediary that links different omics measurements to the same cell. The barcode serves as a common reference point that can be used to associate transcriptomic data, proteomic data, and epigenomic data across different experimental conditions and measurement techniques, thereby managing system complexity through a unifying identifier.
4Productivity
If high-throughput processing is implemented, then tens of thousands of cells can be processed in parallel, but the cost per cell increases
Solution Approach 1:
The system recovers and reuses the barcode information across multiple measurement steps. The barcodes are designed to be read and interpreted without consuming the physical barcode itself, allowing the same barcode to be used for initial cell identification, subsequent omics measurements, and data analysis. This recovery and reuse of barcode information reduces the effective cost per cell by eliminating the need for expensive repeated sequencing of identification markers.
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
This approach enables unprecedented access to molecular regulation mechanisms, improves resolution for rare cell detection, and reduces sequencing costs per cell, facilitating clinical applications and understanding biological complexity.
Implementation Method 1
the nucleic acid strands of the first set are bound to nucleic acid strands of the second set to form a unique nucleic acid barcode
Data Source
AI summary
Provided herein, in some embodiments, are devices, systems and methods for high-throughput single-cell polyomics (e.g., genomic, epigenomic, proteomic and/or phenotypic profile) analyses.