Nanopore-Matched Protein Shuttle for Stable Molecular Trapping
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Solution Overview
Problem
Existing nanopore-based systems face challenges in stably trapping protein shuttles due to complex geometrical and electrical charge structures, leading to instability and noise in molecular trapping and monitoring.
Innovation Solution
A nanopore sensor system comprising a support structure with a nanopore connecting two fluidic chambers, where a protein shuttle with an electrically charged protein molecule is drawn into the nanopore using a voltage bias, allowing for stable trapping and measurement of ionic current changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a voltage-biased nanopore is used to trap protein shuttles, then molecular monitoring capability is improved, but trapping stability deteriorates due to complex geometrical and electrical charge structures of protein molecules
Solution Approach 1:
The patent introduces a protein shuttle as an intermediary component that mediates between the nanopore and the target molecule. The shuttle consists of a protein molecule with specific geometrical and electrical properties that enable stable trapping in the nanopore, while carrying the target molecule for monitoring. This intermediary structure resolves the contradiction by providing a stable platform that maintains both trapping stability and molecular monitoring capability.
Solution Approach 2:
The patent optimizes specific parameters of the protein shuttle, including its size (comparing molecular dimensions to nanopore aperture), charge characteristics, and structural configuration. By carefully selecting proteins with dimensions slightly larger than the nanopore aperture and appropriate charge properties, the system achieves stable trapping while maintaining the ability to monitor target molecules through the nanopore.
2Manufacturing precision
If artificially reproduced nanopores are used, then nanopore sizing control is improved, but bond stability between nanopore and protein molecule deteriorates
Solution Approach 1:
The protein shuttle acts as an intermediary that bridges the nanopore and target molecule, providing stable interactions through optimized protein-nanopore interfaces. The shuttle's protein structure is selected to complement the nanopore's geometrical and electrical characteristics, ensuring stable bonding while maintaining precise nanopore sizing control.
Solution Approach 2:
The patent applies local quality optimization by selecting protein shuttles with specific local characteristics (charge distribution, surface properties, dimensional features) that match the nanopore's interface properties. This localized matching at the interaction interface enhances bond stability without compromising the overall nanopore sizing precision.
3Measurement precision
If protein shuttles with complex structures are used for molecular monitoring, then monitoring capability is improved, but trapping stability deteriorates
Solution Approach 1:
The system segments the molecular monitoring function into two distinct components: the protein shuttle (for stable trapping) and the target molecule (for monitoring). The shuttle handles the trapping function with optimized stability, while the attached target molecule provides the monitoring capability. This segmentation resolves the contradiction by separating the conflicting requirements into different functional components.
Solution Approach 2:
The protein shuttle serves as an intermediary that carries the target molecule while maintaining stable trapping. The shuttle's structure is optimized for stability, and it provides a platform for attaching target molecules that need to be monitored. This intermediary approach allows the system to achieve both stable trapping and effective monitoring without requiring the trapped molecule itself to have complex structures.
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
The system enables stable trapping and analysis of protein shuttles, allowing for precise monitoring of ionic current changes and facilitating the study of target molecules attached to the protein shuttle.
Implementation Method 1
The electrically charged protein molecule can have a radial extent that is at least as large as a smallest diameter of a lumen of the at least one nanopore
Implementation Method 2
The at least one nanopore can be disposed in the support structure... configured to apply a voltage between the first fluidic chamber and the second fluidic chamber
Implementation Method 3
The circuit can be configured to measure ionic current flow through the at least one nanopore between the first fluidic chamber and the second fluidic chamber
Data Source
AI summary
Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.