Spatial Genomic Analysis via Barcoded Oligonucleotide Transfer
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Solution Overview
Problem
Current methods for analyzing mRNA and DNA in complex tissue samples, such as next-generation sequencing, lose spatial context and require laborious steps, making it difficult to detect genes in specific locations within cells effectively.
Innovation Solution
A system and method for transferring genetic material from a tissue or cell sample to a surface with spatially specific oligonucleotides, allowing for high-resolution analysis and detection of genetic modifications by hybridization and imaging, using a device with a high-density oligonucleotide array for precise localization and sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Difficulty of detecting and measuring
If next-generation sequencing methods are used to analyze mRNA and DNA, then gene detection capability is improved, but spatial context is lost
Solution Approach 1:
The patent creates a spatial map by transferring genetic material to a surface that replicates the original tissue architecture. Barcoded oligonucleotides are deposited at locations corresponding to their original spatial positions, creating a copy that preserves both genetic information and spatial context for subsequent sequencing analysis
Solution Approach 2:
The patent introduces a spatial mapping surface with barcoded oligonucleotides as an intermediary between the tissue sample and sequencing analysis. This intermediary captures and preserves spatial information that would otherwise be lost during nucleic acid extraction, enabling both gene detection and spatial context retention
2Difficulty of detecting and measuring
If laborious separation steps are performed to extract nucleic acids from tissue, then gene detection is enabled, but spatial information is lost and processing time increases
Solution Approach 1:
The patent performs preliminary spatial mapping by depositing barcoded oligonucleotides at tissue-corresponding locations before sequencing. This preliminary action preserves spatial information in advance, eliminating the need for complex post-extraction spatial reconstruction and reducing overall processing time
Solution Approach 2:
The spatial architecture of the tissue is copied onto a solid surface through precise deposition of barcoded oligonucleotides. This copying process creates a permanent spatial record that simplifies subsequent analysis and eliminates time-consuming spatial reconstruction steps
3Measurement precision
If high resolution spatial analysis is achieved through transfer to surface, then spatial context is maintained, but device complexity increases
Solution Approach 1:
The patent segments the complex task of spatial genomic analysis into distinct functional modules: tissue imaging for spatial mapping, oligonucleotide deposition for barcode assignment, genetic material transfer for nucleic acid capture, and sequencing for gene detection. This segmentation manages device complexity by organizing functions into manageable, independent components
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 detection of all genes and genetic modifications in specific cells within a tissue section at high resolution, maintaining spatial context and allowing for precise mapping of genetic signatures back to their original location, facilitating improved diagnostic decision-making.
Implementation Method 1
A system and method for transferring genetic material from a tissue or cell sample to a surface with spatially specific oligonucleotides, allowing for high-resolution analysis and detection of genetic modifications by hybridization and imaging
Data Source
AI summary
Provided are devices and methods for capturing template sample nucleic acids in a spatially specific manner that is coordinated with the original location of the templates in a tissue sample. By preserving spatial information regarding a given sample, the disclosed technology allows for improved diagnostics as well as improved therapeutic decision making for patient care and therapy.