Nucleic Acid Barcode Detection Molecules for High-Throughput T-Cell Analysis
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Solution Overview
Problem
Current methods for detecting and isolating antigen-specific T-cells are limited in their ability to handle the vast diversity of T-cell receptors and often require multiple samples for analysis, with existing technologies struggling to comprehensively analyze antigen-specific T-cell responses due to the limited number of fluorescence labels and the complexity of T-cell recognition.
Innovation Solution
A detection molecule comprising a binding molecule, a linker, and a nucleic acid label, specifically designed to enable the detection and identification of multiple antigen-specific cells in a single sample through the use of barcode sequences that can be revealed by sequencing, allowing for the identification of over 1000 different antigen-specific cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescent labels are used to detect T-cell specificity, then detection capability is improved, but the number of detectable T-cell populations is limited due to the limited number of available fluorescence labels
Solution Approach 1:
The patent uses nucleic acid barcodes as information copies that can be amplified and detected through sequencing. Each binding molecule carries a unique nucleic acid sequence that serves as a digital identifier, allowing thousands of different T-cell populations to be detected simultaneously without being limited by the number of detectable signals, thus resolving the contradiction between detection precision and adaptability
Solution Approach 2:
The patent transitions from using fluorescence intensity as the detection parameter to using nucleic acid sequence identity as the detection parameter. This parameter change enables the system to distinguish between different T-cell populations based on sequence variation rather than signal intensity, allowing for the detection of thousands of distinct populations with high precision
2Adaptability or versatility
If multiple fluorescence labels are used to expand T-cell detection complexity, then the number of detectable populations increases, but device complexity and cost increase
Solution Approach 1:
The patent replaces complex fluorescence detection systems with a simpler nucleic acid sequencing system. By copying the binding molecule's identity information into a nucleic acid barcode that can be amplified and sequenced, the system achieves high multiplexing capability using standard, widely available sequencing technology rather than requiring complex spectral unmixing instruments
Solution Approach 2:
The patent substitutes the optical detection mechanism (fluorescence detection requiring specialized flow cytometers or microscopes) with a biochemical detection mechanism (nucleic acid extraction and sequencing). This substitution dramatically reduces device complexity and cost while enabling detection of thousands of T-cell populations
3Measurement precision
If traditional MHC multimer methods are used, then T-cell specificity can be determined, but multiple samples are required for comprehensive analysis due to limited detection capacity
Solution Approach 1:
The patent merges multiple detection capabilities into a single sample analysis by combining binding molecules with different specificities, each carrying a unique nucleic acid barcode. All barcodes can be extracted and sequenced simultaneously from a single sample, enabling comprehensive analysis of multiple T-cell populations without requiring multiple separate samples or experiments
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 and identification of multiple antigen-specific cells in a single sample, overcoming the limitations of existing technologies by using nucleic acid labels as unique identifiers, thereby facilitating a high-throughput method for antigen-specific T-cell analysis.
Implementation Method 1
a binding molecule (BM), a linker (Li) and a label (La)... recognizing at least one entity or cell, binding at least one entity or cell
Data Source
AI summary
The present invention relates to detection molecules comprising at least one binding molecule, at least one linker and at least one label, and detection methods making use of same. The invention provides a high-throughput method for detection, isolation and/or identification of specific entities or cells.