Spatial Mapping of Cells Using Localization Nucleic Acid Arrays
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Solution Overview
Problem
Current technologies for single-cell analysis in tissues lack the ability to correlate molecular signals with the spatial localization of cells within the original tissue, limiting the understanding of cellular interactions and tumor adaptation mechanisms.
Innovation Solution
A method involving nucleic acid arrays with localization nucleic acids attached to a substrate, allowing for the labeling of individual cells or organelles with a localisation nucleic acid sequence, enabling their dissociation while maintaining positional information, which can be mapped and sequenced to correlate molecular data with original tissue location.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single-cell dissociation is performed to enable individual cell sequencing, then molecular signal measurement capability is improved, but spatial localization information is lost
Solution Approach 1:
The patent applies preliminary action by depositing localization nucleic acids onto the tissue section surface before cell dissociation. These nucleic acids bind to cell surface receptors in advance, establishing positional tags that will persist through subsequent dissociation and sequencing steps, thereby preserving spatial information that would otherwise be lost.
Solution Approach 2:
The patent uses localization nucleic acids as intermediaries between the tissue spatial structure and the dissociated cells. These nucleic acids act as mediators that carry spatial position information from the original tissue location to the individual cells after dissociation, enabling correlation of molecular data with spatial origin.
2Loss of information
If spatial resolution is maintained in tissue sections, then spatial localization information is preserved, but single-cell molecular analysis capability is limited
Solution Approach 1:
The patent applies segmentation by dissociating the tissue into individual cells after preliminary labeling, while maintaining the spatial information through attached localization nucleic acids. This allows separate analysis of each cell's molecular content while preserving its original spatial context, combining the benefits of both spatial and single-cell analysis.
Solution Approach 2:
The localization nucleic acids serve as intermediaries that bridge the spatial tissue architecture and the dissociated single cells. They enable the transfer of spatial information to individual cells, allowing high-resolution molecular analysis of single cells while maintaining correlation with their original spatial positions in the tissue.
3Measurement precision
If current spatial transcriptomics methods are used, then spatial resolution is achieved, but single-cell resolution and complete transcriptome access are limited
Solution Approach 1:
The patent applies preliminary action by pre-labeling cells with localization nucleic acids that contain positional information before performing single-cell sequencing. This preliminary tagging enables the subsequent reconstruction of spatial maps from dissociated cells, achieving both spatial resolution and complete transcriptome access at single-cell level.
Solution Approach 2:
The patent combines segmentation of tissue into individual cells with preliminary spatial labeling. This approach enables analysis of complete transcriptomes at single-cell resolution while preserving spatial information through the attached localization nucleic acids, overcoming the limitations of traditional spatial transcriptomics methods.
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 the accurate mapping and sequencing of individual cells, allowing for the correlation of molecular data with spatial localization, thereby improving the understanding of cellular interactions and tumor mechanisms.
Implementation Method 1
binding of the released nucleic acids comprising the localisation sequence or its complementary sequence, to cells or organelles of the tissue sample via a ligand bound to a receptor or receptors of cells or organelles in the tissue sample
Data Source
AI summary
Method for determining tissue positions using an array, which comprise location sequences, the location sequences bind to the tissue samples via ligands. The tissue section which allows localisation tags to be assigned to areas of the tissue comprising a single or plurality of cells or organelles, e.g. about two to ten cells. By triangulation of the localisation tags it is possible to assign a unique relative position in the tissue per cell or organelle.