Spatial Capture Probe Arrays With Barcoded Analyte Localization
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Solution Overview
Problem
Existing methods fail to provide spatial information on analyte distribution within biological samples, particularly at the single-cell level, and do not account for the position of cells within tissues.
Innovation Solution
The development of spatial arrays using oligonucleotides with 3' ends attached to a substrate, extended with primers, and ligated with capture domains to capture specific analytes, allowing for the determination of their spatial location.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If traditional analyte detection methods are used, then analyte data can be obtained, but spatial information and cell position information within tissue are lost
Solution Approach 1:
The tissue sample is divided into multiple discrete locations or regions, each assigned a unique spatial barcode. Capture probes are positioned at specific locations and tagged with barcodes corresponding to their spatial coordinates, enabling reconstruction of the spatial map from the segmented data
Solution Approach 2:
Spatial barcodes serve as intermediary elements that link the physical location in tissue to the detected analyte. The barcodes are incorporated into capture probes or oligonucleotides, acting as mediators that carry spatial information through the detection process without interfering with analyte binding
2Quantity of substance
If single-cell analyte data is collected, then detailed analyte information is obtained, but the position of cells within the parent tissue sample is not provided
Solution Approach 1:
The method combines single-cell analyte detection capabilities with spatial mapping by integrating barcode sequences into the capture probe structure. Each capture probe simultaneously performs analyte capture and spatial identification, merging two functions into a single system
Solution Approach 2:
The invention adds a spatial dimension to traditional analyte detection by incorporating barcode sequences that encode positional information. This transforms the detection from a one-dimensional analyte measurement to a multi-dimensional data set including spatial coordinates
3Productivity
If capture probes are designed to capture substantial population of analytes, then high analyte capture efficiency is achieved, but specific gene analyte capture capability is reduced
Solution Approach 1:
The capture probe array implements local quality by assigning different capture specificities to different spatial locations. Some regions use probes optimized for capturing abundant analytes, while other regions use probes with high specificity for rare or specific gene analytes, allowing both goals to be achieved in different parts of the system
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 precise identification and localization of analytes, such as RNA, DNA, and proteins, within biological samples, providing detailed spatial information about their distribution and interaction within tissues.
Implementation Method 1
providing a splint oligonucleotide that hybridizes to the 3' end of the first oligonucleotide
Data Source
AI summary
The present disclosure relates to compositions and methods for generating capture probes on a substrate for identifying the location of analytes in a biological sample.