Nucleic Acid Nanopore Geometry for Analyte Binding
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Solution Overview
Problem
Current point-of-care diagnostic technologies face challenges in achieving high accuracy and reliability, particularly in detecting large biomolecular analytes like antibodies and pathogens, due to limitations in nanopore design and the risk of false negative or false positive results, which is exacerbated by the need for rapid and efficient testing during pandemics like SARS-CoV-2.
Innovation Solution
The development of novel nucleic acid nanopores with customized geometries that conform to the three-dimensional shape of specific analytes, incorporating an analyte binding moiety within the nanopore to enhance the sensitivity and specificity of electrical signal measurements upon analyte binding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional nanopore designs are used, then device complexity is reduced, but measurement precision and reliability deteriorate due to inability to accommodate large biomolecular analytes effectively
Solution Approach 1:
The nanopore is segmented into distinct functional regions: a cis-facing aperture for analyte entry, a trans-facing aperture for exit, and a central sensing region with binding moiety. This segmentation allows each region to be optimized for its specific function, improving measurement precision while maintaining manageable device complexity through modular design
Solution Approach 2:
The nanopore employs local quality by creating a geometry with different dimensions at different locations: wider apertures (3-20 nm) for analyte accommodation and a narrower central region (1-3 nm) for sensing. The binding moiety is locally positioned within the central lumen to maximize interaction with captured analytes, enhancing detection accuracy without requiring uniform complexity throughout the structure
2Measurement precision
If nanopore channel lumen is widened to accommodate large biomolecules, then measurement precision improves, but background noise increases reducing reliability
Solution Approach 1:
The nanopore structure implements local quality by having wider apertures (3-20 nm) for analyte capture while maintaining a narrower central lumen region (1-3 nm) for sensing. This geometric variation ensures high sensitivity through adequate analyte accommodation while the constricted sensing region reduces background noise, improving the signal-to-noise ratio and overall reliability
Solution Approach 2:
The binding moiety acts as an intermediary element positioned within the central lumen. It mediates the interaction between the nanopore structure and the analyte, ensuring specific and high-affinity binding. This intermediary mechanism enhances signal sensitivity while maintaining reliability through specific molecular recognition that reduces non-specific background signals
3Adaptability or versatility
If generic nanopore geometry is used, then ease of manufacture is improved, but adaptability to different analyte sizes deteriorates
Solution Approach 1:
The nanopore design employs parameter changes by allowing independent variation of key geometric parameters: aperture diameters (3-20 nm), central lumen dimensions (1-3 nm), and pore length. These adjustable parameters enable adaptation to different analyte sizes and shapes while maintaining ease of manufacture through systematic design rules and modular construction approaches
4Measurement precision
If binding moiety is positioned outside the nanopore, then device complexity is reduced, but measurement precision deteriorates due to reduced analyte capture efficiency
Solution Approach 1:
The binding moiety is nested within the central lumen of the nanopore structure. This nested configuration ensures that the binding moiety is positioned in direct proximity to the analyte capture zone, maximizing binding efficiency and measurement precision. The nested design integrates the binding function seamlessly into the nanopore structure without requiring separate external components, managing device complexity through compact integration
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
This approach enables improved sensitivity and reduced background noise in detecting analytes, leading to more accurate and reliable point-of-care diagnostics by optimizing the geometry of the nanopore to accommodate and bind analytes effectively, thereby enhancing the fidelity of signal readouts.
Implementation Method 1
the nanopore defines a central lumen passing therethrough and wherein the geometry of the nanopore is configured to accommodate all or a part of an analyte molecule within or proximate to the central lumen so as to optimize obstruction of the central lumen by the analyte molecule
Data Source
AI summary
A sensing nucleic acid nanopore is provided. The nanopore possesses a geometry and wherein the nanopore defines a central lumen passing therethrough. The geometry of the nanopore is configured to accommodate all or a part of an analyte molecule within, or proximate to, the central lumen so as to optimize obstruction of the central lumen by the analyte molecule. Methods for enhancing binding of an analyte molecule to a membrane-spanning nanopore are provided. Membranes, sensor devices and methods for molecular sensing comprising the sensing nucleic acid nanopores are also provided.