Blocking-Strand Nucleic Acid Labels for Specific Proximity Detection
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Solution Overview
Problem
Existing biological sample analysis methods face challenges with cross-reactivity of affinity reagents, leading to false-positive events and reduced specificity, particularly in multiplex assays requiring large sets of distinguishable markers.
Innovation Solution
A Proximity Hybridization Assay (PHA) using a label comprising a first and second label part with nucleic acid backbones, where a blocking strand controls hybridization to form a duplex only when affinity reagents are in close proximity, allowing for controlled detection of analyte proximities and mitigating cross-reactivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If affinity reagents are used for detecting target analytes, then detection capability is provided, but cross-reactivity occurs leading to false-positive events and reduced specificity
Solution Approach 1:
The patent introduces a blocking strand as an intermediary element that mediates between the label parts and the target analyte. The blocking strand specifically binds to the target analyte and prevents the affinity reagent from binding to off-target molecules, thereby eliminating cross-reactivity while maintaining detection capability
Solution Approach 2:
The label is divided into multiple label parts (first label part and second label part) that are separated by a blocking strand. This segmentation allows each label part to be independently controlled, enabling the blocking strand to prevent false-positive binding while the label parts remain ready to detect the target when properly positioned
2Adaptability or versatility
If large sets of markers are assembled from individual components, then multiplexing capability is enhanced, but handling complexity increases
Solution Approach 1:
The patent creates a universal label structure that can function with multiple different affinity reagents and target analytes. The blocking strand and label parts form a modular system that can be adapted to various detection scenarios, enabling multiplexing while maintaining standardized handling procedures
Solution Approach 2:
The label parts are pre-assembled with blocking strands in a controlled manner before use. This preliminary assembly ensures that the complex multi-component system is pre-configured to minimize handling complexity during actual detection, while still providing the versatility needed for multiplexing
3Ease of operation
If label parts are kept separate to reduce complexity, then handling is simplified, but detection reliability decreases due to uncontrolled hybridization
Solution Approach 1:
The blocking strand acts as a mediator that controls the interaction between separated label parts. It prevents uncontrolled hybridization by physically blocking the binding interface, while still allowing the label parts to remain separate and easy to handle until detection is required
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
Enhances assay specificity by reducing false-positive events and enabling precise detection of analyte proximities, suitable for detecting protein-protein interactions and post-translational modifications with high spatial and temporal resolution.
Implementation Method 1
The first nucleic acid strand and the second nucleic acid strand are configured to form a duplex
Implementation Method 2
The label further comprises at least one blocking nucleic acid strand, which is at least partially complementary to one of the first nucleic acid strand and the second nucleic acid strand
Data Source
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AI summary
A label for analysing a biological sample is provided. The label comprises a first label part comprising a first nucleic acid strand (106) and a second label part comprising a second nucleic acid strand (110). The first nucleic acid strand (106) and the second nucleic acid strand (110) are configured to form a duplex. The label further comprises at least one first labelling moiety (108) and at least one second labelling moiety (112), and the label further comprises at least one blocking nucleic acid strand (126, 128). In further aspects, a marker (100, 500, 600) comprising the label and a respective method are provided.