Barcode Diffusion Mapping for High-Resolution Spatial Omics
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Solution Overview
Problem
Current methods for capturing the spatial arrangement and conformation of biomolecules within cells and tissues are limited, as they often require specific biomolecules and are not generalizable for arbitrary biomolecular distributions.
Innovation Solution
The method involves providing node factories on a biological sample with node nucleic acids containing a node barcode region and flanking regions, amplifying these nucleic acids to generate concatemers, and allowing them to diffuse and concatenate with other node nucleic acids, forming unique barcode combinations that provide spatial mapping information.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If node factories with node nucleic acids are used for spatial mapping, then spatial mapping precision is improved, but device complexity increases
Solution Approach 1:
The spatial mapping system is segmented into discrete node factories, each containing specific node nucleic acids with unique barcodes. Each node factory acts as an independent spatial marker that can be individually tracked, allowing high-resolution spatial mapping through the collective information from multiple segmented nodes rather than requiring a single complex mapping system.
Solution Approach 2:
Node nucleic acids serve as intermediary molecules that bridge the gap between physical spatial locations and detectable signals. These nucleic acid-based intermediaries carry barcode information that encodes spatial position, enabling precise spatial mapping through sequence analysis rather than direct physical measurement, thus improving precision while managing system complexity.
2Area of stationary object
If concatemers diffuse away from node locations to provide spatial information, then spatial coverage is improved, but measurement precision deteriorates
Solution Approach 1:
The system employs local quality by assigning unique barcode sequences to node nucleic acids based on their specific spatial locations. Each node factory produces concatemers with barcodes that encode local spatial information, allowing the system to maintain high spatial resolution even as concatemers diffuse throughout the tissue. The local spatial identity is preserved through the barcode sequence rather than physical position.
Solution Approach 2:
Node nucleic acids are amplified into concatemers that carry copies of the original spatial information encoded in their barcodes. This copying mechanism allows the spatial information from a single node location to be distributed throughout the tissue via diffusion, improving spatial coverage while maintaining measurement precision through the fidelity of the barcode copy.
3Quantity of substance
If node nucleic acids are amplified to generate concatemers, then signal strength is improved, but loss of substance increases
Solution Approach 1:
The system changes the parameter of nucleic acid quantity by amplifying node nucleic acids into multiple concatemer copies through controlled amplification reactions. This parameter change increases the detectable signal strength by generating abundant concatemers from limited initial node nucleic acids, while the amplification is controlled to minimize excessive consumption of the original node nucleic acid pool.
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 high-resolution spatial mapping of biomolecules from the angstrom scale to the millimeter scale, providing a generalizable method for capturing complex molecular interactions within biological samples.
Implementation Method 1
amplifying the one or more node nucleic acids to generate concatemers of node nucleic acids, wherein the concatemers diffuse away from the node locations over time
Data Source
AI summary
Provided herein are compositions, kits, and methods for collection, integration and analysis of various facets of information from tissues at the cellular or subcellular level. Information includes spatial mapping from nucleic acid barcodes to reconstruct location of nodes of nucleic acid barcode generation in a sample. In some workflows, light-based technologies are incorporated for an additional layer of selective spatial tagging of regions. In further steps, such tags are optionally analyzed by high throughput imaging or Next Generation Sequencing.