Deconvolved Spatial Barcode Arrays for Tissue Feature Localization
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Solution Overview
Problem
Existing methods for studying spatial heterogeneity in tissues fail to provide comprehensive data on the position of single cells within biological samples, limiting the understanding of cell morphology, differentiation, and analyte levels.
Innovation Solution
A method involving spatially resolved arrays with barcoded oligonucleotides is used to determine the location of features on arrays by aligning and hybridizing barcoded oligonucleotides, allowing for the identification of specific features and their positions, and correlating analytes with spatial locations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If spatially resolved measurements are performed to assess spatial heterogeneity, then information on cell position and morphology is obtained, but difficulty in correlating captured analytes with specific spatial locations arises
Solution Approach 1:
The method segments the spatial information by assigning unique barcoded oligonucleotides to specific locations on the array. Each barcode acts as a discrete identifier that divides the continuous spatial information into separable, detectable units that can be independently tracked and correlated with captured analytes.
Solution Approach 2:
Barcoded oligonucleotides serve as intermediary elements that bridge the captured analytes and their spatial locations. The barcodes are incorporated into the captured material and then used as mediators to map back to the original spatial position on the array through sequence determination, solving the correlation difficulty.
2Measurement precision
If barcoded oligonucleotides are used to track spatial locations, then spatial resolution is improved, but the complexity of the array system increases
Solution Approach 1:
Instead of physically marking each spatial location with complex structures, the method creates information copies in the form of barcoded oligonucleotide sequences. These sequence-based copies encode spatial location information that can be read and decoded without adding physical complexity to the array structure itself.
Solution Approach 2:
The patent replaces potential mechanical or physical marking systems with a biochemical information system. Spatial location is encoded through nucleic acid sequences rather than physical tags or markers, allowing for high-resolution tracking through sequence determination rather than mechanical detection 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 high-resolution spatial analysis of analytes within tissues, providing detailed information on cell morphology and function, and aiding in treatment selection and disease mechanism understanding.
Implementation Method 1
hybridizing the first barcoded oligonucleotide to the second barcoded oligonucleotide, thereby producing a combined nucleic acid comprising the first and second spatial barcodes
Data Source
AI summary
Methods for determining a location of a feature on an array include: (a) providing a first array with a first plurality of features immobilized on a first substrate; (b) providing a second array with a second plurality of features immobilized on a second substrate; (c) aligning the first array with the second array; (d) hybridizing a first barcoded oligonucleotide of the first array to a second barcoded oligonucleotide of the second array, thereby producing a combined nucleic acid that includes first and second spatial barcodes; (e) determining all or a portion of the sequence of the combined nucleic acid; and (f) identifying the second barcoded oligonucleotide associated with the first barcoded oligonucleotide in the combined nucleic acid, and determining the location of a second feature in the second array.