Spatial Barcodes for Single Cell Sequencing Position Encoding
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Solution Overview
Problem
Current single cell sequencing technologies lack the ability to encode and retain spatial information about the origin of cells within a tissue or specimen, limiting the understanding of cellular interactions and tissue function.
Innovation Solution
The Single Cell Spatial Analysis System encodes spatial position information by using spatial barcodes attached to beads or surfaces, integrating this information into DNA or RNA sequencing, allowing for the decoding of cellular origin and spatial relationships within the tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If single cell sequencing is performed without spatial encoding, then sequencing throughput and analysis capability are improved, but spatial position information is lost
Solution Approach 1:
The patent applies preliminary action by encoding spatial position information into barcodes before the cells undergo sequencing analysis. Spatial barcodes are assigned to cells or cell groups prior to sequencing, allowing the spatial data to be preserved through the sequencing process without interfering with the sequencing throughput. This preliminary encoding ensures that spatial information is not lost during high-throughput processing.
Solution Approach 2:
The patent uses spatial barcodes as intermediary elements that carry spatial position information independently of the sequencing data. These barcodes act as mediators between the physical spatial location of cells and the digital sequencing results, enabling simultaneous high-throughput sequencing while preserving spatial context through the barcode intermediary.
2Loss of information
If spatial barcodes are added to cells, then spatial position information is retained, but sample processing complexity increases
Solution Approach 1:
The patent merges the spatial encoding function with existing single-cell sequencing workflows by integrating spatial barcodes into the standard library preparation process. The spatial barcodes are incorporated alongside cellular barcodes and molecular identifiers, combining multiple functions into a unified sequencing workflow that does not significantly increase processing complexity despite adding spatial information capability.
Solution Approach 2:
The patent designs spatial barcodes to serve multiple functions: they encode spatial position information, are compatible with existing sequencing platforms, and can be integrated with cellular and molecular barcoding systems. This multi-functionality reduces the need for separate processing steps and minimizes the increase in sample processing complexity.
3Loss of information
If manual cell collection methods are used, then spatial information can be captured, but throughput is limited
Solution Approach 1:
The patent replaces manual mechanical cell collection methods with automated microfluidic systems that can rapidly dispense cells or cell groups in controlled sequences. This mechanical substitution enables high-throughput spatial encoding by automatically positioning and collecting cells according to their spatial location in the tissue, eliminating the bottleneck of manual collection while preserving spatial information through automated tracking.
Data Source
AI summary
A system, methods, and apparatus are described to collect and prepare single cells and groups of cells from microsamples of specimens and encode spatial information of the physical position of the cells in the specimen. In some embodiment, beads or surfaces with oligonucleotides containing spatial barcodes are used to analyze DNA or RNA. The spatial barcodes allow the position of the cell to be defined and the nucleic acid sequencing information, such as target sequencing, whole genome, gene expression, used to analyze the cells in a microsample for cell type, expression pattern, DNA sequence, and other information, in the context of the cell's physical position in the specimen. In other embodiment, markers such as isotopes are added to a microsample to encode spatial position with mass spectoscopy or other analysis. The spatial encoded information is then readout by analysis such as DNA sequencing, mass spectrometry, fluorescence, or other methods.