Spatially Barcoded Nucleic Acid Probes for Localized Multiplex Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current genomic analysis tools lack the ability to distinguish spatial information of nucleic acids within biological specimens, leading to loss of important differences between individual cells and subpopulations of cancer cells, which can result in ineffective cancer treatments.
Innovation Solution
A method for spatially tagging nucleic acids by attaching probes with unique barcode sequences to a solid support, hybridizing them with target nucleic acids, and extending these probes to include both barcode and target sequences, thereby preserving spatial information.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If conventional genomic analysis tools are used to analyze nucleic acids, then nucleic acid detection is achieved, but spatial information of nucleic acids is lost
Solution Approach 1:
The solid support is divided into multiple discrete locations or regions, each capable of preserving spatial information about nucleic acids detected at specific positions. This segmentation allows different areas of the support to maintain distinct spatial data, resolving the contradiction between achieving comprehensive nucleic acid detection and preserving spatial information.
Solution Approach 2:
The solid support acts as an intermediary carrier that simultaneously holds nucleic acid probes and preserves their spatial positions. By using the solid support as a mediator between nucleic acid detection and spatial information storage, the system achieves both detection capability and spatial preservation without requiring entirely separate systems.
2Adaptability or versatility
If nucleic acid probes are randomly located on solid support, then multiplex detection capability is improved, but spatial precision of detection is reduced
Solution Approach 1:
Different regions or locations on the solid support are assigned different functions - some locations hold probes for specific target nucleic acids while maintaining their spatial coordinates. This local differentiation allows the system to achieve both multiplex detection (through diverse probe types) and spatial precision (through location-based identification).
Solution Approach 2:
The system adds a spatial dimension to the nucleic acid detection data by recording the physical location of each probe on the solid support. This dimensional addition allows random probe distribution for multiplex capability while simultaneously providing precise spatial information through coordinate tracking, resolving the contradiction between versatility and precision.
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
Preserves spatial information of nucleic acids within biological specimens, allowing for localized detection and characterization of cells, including identification of specific alleles, epigenetic signatures, and gene expression levels, enhancing cancer treatment efficacy by identifying resistant cell populations.
Implementation Method 1
hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen that are proximal to the randomly located probes
Data Source
Figure 1A~1B
Figure 2A~2C
Figure 3
AI summary
A method for spatially tagging nucleic acids of a biological specimen, including steps of (a) providing a solid support comprising different nucleic acid probes that are randomly located on the solid support, wherein the different nucleic acid probes each includes a barcode sequence that differs from the barcode sequence of other randomly located probes on the solid support; (b) performing a nucleic acid detection reaction on the solid support to locate the barcode sequences on the solid support; (c) contacting a biological specimen with the solid support that has the randomly located probes; (d) hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen; and (e) modifying the randomly located probes that are hybridized to the target nucleic acids, thereby producing modified probes that include the barcode sequences and a target specific modification, thereby spatially tagging the nucleic acids of the biological specimen.