Cellular Sample Barcoding With Concatenates for Spatial Cell Indexing
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Solution Overview
Problem
Existing methods for analyzing cellular samples face challenges in distinguishing between different cell types and states, particularly in densely packed tissues, and managing large datasets from single-cell analysis, which complicates data interpretation and reproducibility.
Innovation Solution
Introduce a plurality of nucleic acid barcode elements into cells, generating a concatenate to index and track individual cells, using anchor elements for secure attachment and optical detection, and perform sequencing to associate spatial and genetic information.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional bulk analysis techniques are used, then the analysis process is simple, but the resolution between different cell types and states is lost
Solution Approach 1:
The patent applies segmentation by introducing individual barcode elements into separate cells, allowing each cell to be uniquely identified and tracked. This divides the bulk sample into individually identifiable units, enabling resolution of cell type distinctions while maintaining manageable analysis complexity through systematic indexing
Solution Approach 2:
The patent uses barcode elements as intermediary molecules that bridge the gap between physical cells and digital data. These barcodes serve as mediators that encode cell identity information, enabling precise cell type distinction without requiring complex direct observation methods
2Measurement precision
If single-cell analysis techniques are used, then the data resolution and cell type distinction are improved, but the computational complexity and data management difficulty increase
Solution Approach 1:
The patent applies preliminary action by pre-introducing and pre-indexing barcode elements into cells before analysis. This preliminary indexing step organizes cell identity information in advance, reducing the computational burden during subsequent analysis by providing pre-structured identification data rather than requiring complex real-time characterization
Solution Approach 2:
The patent uses barcode elements as informational copies that represent cell identity. Instead of directly analyzing complex cell states computationally, the system creates simplified digital copies through barcodes that encode cell information, reducing computational complexity while maintaining identification accuracy
3Reliability
If barcode elements are introduced into cells, then the cell identification and tracking accuracy are improved, but the sample preparation complexity increases
Solution Approach 1:
The patent merges the barcode element with the cell through introduction into the cell cytoplasm or nucleus. This combining approach integrates the identification function directly into the cell itself, improving tracking reliability while simplifying preparation by eliminating the need for separate labeling steps
Solution Approach 2:
The barcode elements are designed to be self-retaining within cells through their introduction and stabilization in the cellular environment. This self-service characteristic allows the barcodes to maintain their identification function without requiring external intervention or complex preparation protocols
Data Source
AI summary
A method for indexing a cellular sample is provided. The method includes introducing a plurality of nucleic acid barcode elements into at least one cell of the cellular sample. The method further includes generating a concatenate of at least some of the nucleic acid barcode elements in the at least one cell.