Multiplexed Spatial Capture of Analytes in Biological Samples
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Solution Overview
Problem
Current multiplex methods struggle to determine the presence and spatial location of multiple analytes in biological samples, such as tissue sections, due to the different experimental conditions required for capturing different types of analytes, like nucleic acids and proteins.
Innovation Solution
The method involves using an array with capture probes that include spatial barcodes and capture domains, antigen-binding complexes with oligonucleotide barcodes, and capture oligonucleotides to identify and locate analytes, allowing for simultaneous or sequential capture of multiple analytes while maintaining their spatial context.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If different experimental conditions are used to capture different types of analytes, then capture efficiency for each analyte type is improved, but the complexity of the multiplex method increases
Solution Approach 1:
The method segments the capture process into distinct phases: first capturing nucleic acids under optimized nucleic acid capture conditions, then capturing proteins under optimized protein capture conditions. Each analyte type is captured in its own phase with dedicated reagents and conditions, ensuring high capture efficiency for each while managing overall complexity through structured segmentation
Solution Approach 2:
The method performs preliminary capture of nucleic acids before protein capture. By first capturing nucleic acids and removing them from the sample, the system prepares the sample for subsequent protein capture under different conditions. This preliminary action prevents interference between the two capture processes and maintains optimal conditions for each analyte type
2Productivity
If multiple analytes are captured simultaneously, then productivity is improved, but measurement precision deteriorates
Solution Approach 1:
The method uses spatial barcodes as intermediaries to link captured analytes to their original spatial locations. Each capture probe contains a spatial barcode that records the position information. This intermediary mechanism allows simultaneous capture of multiple analytes while preserving precise spatial location data through the barcode system, preventing loss of spatial information in multiplexed assays
Solution Approach 2:
The method creates copies of spatial information through spatial barcodes. Instead of directly measuring the physical location of multiple analytes simultaneously, the system captures analytes and creates barcode copies that encode their original positions. This copying approach enables multiplexed capture while maintaining measurement precision through the encoded spatial information
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
This approach enables the determination of the location and abundance of multiple analytes at high spatial resolution, providing comprehensive data on analyte distribution within biological samples while retaining native spatial context.
Implementation Method 1
a first capture probe of the plurality of capture probes includes: (i) a first spatial barcode, and (ii) a first capture domain that hybridizes to a first analyte capture sequence
Implementation Method 2
an antigen-binding complex of the plurality of antigen-binding complexes includes: (1) an antigen-binding moiety that binds a first analyte
Implementation Method 3
a capture oligonucleotide of the plurality of capture oligonucleotides includes: (1) a sequence substantially complementary to the analyte-binding moiety barcode, or a portion thereof
Implementation Method 4
a first probe of the plurality of first probes includes a sequence substantially complementary to a sequence of a second analyte and hybridizes to the second analyte
Data Source
AI summary
Provided herein are methods, compositions, and kits for multiplex spatial detection of analytes in a biological sample.