Hydrogel DNA-Barcode Antibody Method for Multifactorial Interaction Detection
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Solution Overview
Problem
Current methods are unable to conveniently analyze multifactorial interactions in biological samples, particularly in small amounts of cells or tissues, which are crucial for understanding complex interactions related to tumor growth and refractory conditions, as well as interactions among various cell types in tumor microenvironments.
Innovation Solution
A method involving DNA barcode-labeled antibodies, embedding the sample in a hydrogel, and performing a nucleic acid amplification reaction using specific primers to detect interactions by analyzing the nucleotide sequences of amplification products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional biochemical analysis or microscopic analysis is used to investigate multifactorial interactions, then interaction information can be obtained, but a large quantity of cells or tagged protein expression is required
Solution Approach 1:
The patent introduces DNA barcodes as intermediary molecules that bridge antibodies and sequencing technology. Each antibody is labeled with a unique DNA barcode, allowing interaction information to be captured and amplified through nucleic acid amplification reactions, thereby enabling detection in small sample quantities without requiring tagged protein expression
Solution Approach 2:
The patent replaces conventional biochemical analysis methods with a nucleic acid-based detection system. By converting antibody-antigen interaction information into DNA barcode sequences that can be amplified and sequenced, the method substitutes mechanical/biochemical detection with molecular biology-based detection that offers higher sensitivity for small samples
2Loss of information
If conventional methods are used to assess tumor tissues, then histological or genomic information can be obtained, but quantitative analysis of factor interactions is not possible
Solution Approach 1:
The patent creates a universal platform that can simultaneously detect multiple factor interactions by using different DNA barcodes for different antibodies. The same amplification and sequencing workflow can analyze various combinations of factors (e.g., PD-1/PD-L1, MYC interactions, tumor microenvironment cell interactions) without requiring separate specialized methods for each interaction type
Solution Approach 2:
The patent segments the complex interaction analysis into distinct components: unique DNA barcodes for each antibody, specific primers for amplification, and sequencing analysis. This segmentation allows systematic investigation of multiple interactions while maintaining quantitative capability and reducing overall analytical complexity
3Measurement precision
If existing sequencing-based antibody binding methods are used, then binding information can be obtained, but multifactorial interactions among multiple factors cannot be analyzed
Solution Approach 1:
The patent merges multiple single-factor detection methods into a unified multifactorial interaction analysis platform. By combining DNA barcode-labeled antibodies with multiplexed nucleic acid amplification using specific primers, the system can simultaneously detect and quantify interactions among multiple factors in the same sample, enabling comprehensive analysis of complex biological systems
Data Source
AI summary
The present invention provides a method for identifying multifactorial interactions in a biological sample, comprising (a) selecting a plurality of analytical target factors, (b) labeling antibody molecules against each of the selected factors with DNA barcodes, (c) contacting a biological sample containing the analytical target factors with the antibody molecules labeled with the DNA barcodes, (d) embedding the biological sample in a hydrogel after step (c), (e) performing, within the hydrogel, a nucleic acid amplification reaction using a plurality of primers designed such that, when two antibodies come in close proximity, the primers produce an amplification product containing both DNA barcode sequences from the antibodies, and (f) analyzing a nucleotide sequence of the produced amplification product to detect a presence of a factor that simultaneously interacts with two or more factors.