Spatial Mapping of Tissue Nucleic Acids via Barcoded Oligonucleotide Probes
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Solution Overview
Problem
Current methods for spatial mapping of nucleic acids in tissue samples are limited by high costs and inefficiencies due to the need for extensive molecular testing, which can dilute tumor-specific DNA and RNA signals from surrounding cells, leading to loss of diagnostic information on tumor heterogeneity and tissue architecture.
Innovation Solution
A method using oligonucleotide probes with barcode sequences that bind specifically to nucleic acids in tissue samples, allowing for high spatial resolution mapping without the need for extensive probe sets, by identifying regions of interest and applying probes individually based on tissue information, enabling efficient multiplexing and cost-effective analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If regions of interest are removed from the slide for molecular analysis, then molecular diagnostic accuracy is improved, but spatial information and tissue architecture are lost
Solution Approach 1:
The tissue sample is divided into multiple discrete regions of interest (ROIs) that are spatially separated and individually analyzed. Each ROI is assigned a unique barcode identifier, allowing molecular analysis to be performed on separated regions while maintaining the ability to reconstruct the spatial map of the original tissue architecture.
Solution Approach 2:
Barcodes containing spatial location information are embedded within the molecular analysis workflow. The barcodes are incorporated into the nucleic acid samples during processing, nesting the spatial identification code within the molecular material itself, so that spatial information is preserved throughout the analysis process.
2Measurement precision
If extensive molecular testing is performed to achieve high spatial resolution mapping, then mapping precision is improved, but costs and analysis time increase significantly
Solution Approach 1:
A universal barcode system is implemented that can identify multiple regions of interest using a standardized set of barcode sequences. This single system serves multiple functions: spatial identification, sample tracking, and data integration, eliminating the need for separate identification systems for each region and reducing overall analysis complexity.
Solution Approach 2:
The system changes the parameter of spatial resolution by adjusting the density and distribution of barcoded ROIs rather than increasing the complexity of molecular testing. By optimizing the number and placement of barcoded regions, high spatial mapping precision is achieved with reduced molecular analysis requirements.
3Quantity of substance
If tumor-specific nucleic acids are analyzed in bulk tissue samples, then molecular signal detection is improved, but spatial heterogeneity information is diluted
Solution Approach 1:
Regions of interest containing tumor-specific nucleic acids are extracted and separated from the surrounding stromal and immune cells. By isolating specific ROIs and analyzing them individually with barcode identification, the tumor signal is enriched while spatial heterogeneity information is preserved through the barcode map that records the original location of each analyzed region.
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 provides a cost-effective and precise spatial mapping of nucleic acids, preserving diagnostic information on tumor heterogeneity and tissue architecture, while maintaining the multiplexing capabilities of next-generation sequencing, thus enhancing diagnostic accuracy.
Implementation Method 1
The method is based on the application of patterns of oligonucleotide probes comprising a barcode sequence that bind to the nucleic acids in the sample
Data Source
AI summary
A method is presented that enables the spatial mapping of nucleic acids of tissue samples with high resolution and without sacrificing the degree of multiplexing that is available from next-generation sequencing. The method is based on the application of patterns of barcoded oligonucleotides probes onto predefined locations in a region of interest in a tissue sample. Every nucleic acid analyzed can be allocated to a certain position inside the sample based on the barcode. Various printing technologies can be used and different ways of patterning can be employed, like a regular array with a certain pitch or alternatively an object-based patterning with defined regions of interest without shape constraints.