Motor-Controlled Nanopore Carriers for Multiplex Detection
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Solution Overview
Problem
Current detection techniques for biomarkers such as proteins and miRNAs are limited by low sensitivity, especially at low concentrations, and require extensive sample preparation, making them clinically inaccessible for multiplexed analysis in complex samples.
Innovation Solution
A method utilizing nanopore technology with carriers containing a single-stranded leader, identifier region, and molecule-binding region, controlled by a motor protein, allows for highly multiplexed detection of multiple molecules directly in unprocessed samples through optical or electrical measurements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If antibody-based detection techniques are used, then detection specificity is improved, but sensitivity at low concentrations deteriorates
Solution Approach 1:
The invention embeds multiple functional regions within a single carrier molecule: a leader region for nanopore translocation, an identifier region for target-specific binding (antibody/aptamer), and a payload region for signal generation. This nested structure allows the carrier to simultaneously achieve specific target recognition and enhanced detection sensitivity at low concentrations, resolving the contradiction between specificity and sensitivity.
Solution Approach 2:
The carrier is constructed as a composite molecular structure combining different functional elements: binding moieties (antibodies or aptamers) for specific target recognition, motor proteins for controlled translocation, and identifier regions for detection. This composite design enables the system to maintain high specificity while achieving superior sensitivity at low analyte concentrations compared to conventional antibody-based methods.
2Measurement precision
If mass-spectrometry-based technologies are used, then detection accuracy is improved, but sample preparation complexity increases
Solution Approach 1:
The carrier molecules are pre-assembled with all necessary functional components (binding regions, motor proteins, identifier regions) before sample analysis. This preliminary preparation eliminates the need for complex sample processing steps during actual detection, allowing direct analysis of crude samples while maintaining high detection accuracy comparable to mass-spectrometry methods.
Solution Approach 2:
The invention extracts and integrates the essential detection functions into a single carrier molecule, removing the need for extensive sample preparation steps required by mass-spectrometry. The carrier directly binds target molecules in crude samples and transports them through the nanopore for immediate detection, eliminating complex preprocessing while maintaining detection accuracy.
3Measurement precision
If DNA carriers are used for selective detection, then detection specificity is improved, but multiplexing capability deteriorates
Solution Approach 1:
The carrier is divided into distinct functional segments: a leader region for translocation, separate identifier regions for different target specificities, and a payload region. Each carrier type can be designed with specific identifier sequences for different targets, enabling a library of carriers to detect multiple analytes simultaneously through a single nanopore, thus achieving multiplexing while maintaining high specificity for each target.
Solution Approach 2:
The carrier design provides universal functionality for detecting multiple different targets using the same basic platform. By varying the identifier region sequences while maintaining the same carrier architecture and translocation mechanism, the system can detect multiple analytes (proteins, miRNAs, other molecules) simultaneously, achieving both high specificity and multiplexing capability.
4Device complexity
If conventional detection methods are used, then equipment simplicity is maintained, but detection sensitivity at low concentrations deteriorates
Solution Approach 1:
The carrier acts as an intermediary that amplifies the detection signal. Each carrier is designed to produce a measurable electrical signal as it translocates through the nanopore, and the presence of bound target molecules modifies this signal in detectable ways. This intermediary approach enables sensitive detection of low-concentration analytes using relatively simple nanopore equipment without requiring complex instrumentation.
Solution Approach 2:
The invention replaces complex mechanical/optical detection systems with an electrical measurement approach based on nanopore translocation. As carriers pass through the nanopore, they generate characteristic electrical current blockades that can be measured with simple electrophysiological equipment. This substitution maintains equipment simplicity while dramatically improving detection sensitivity at low concentrations compared to conventional methods.
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 sensitive detection of proteins and miRNAs at low concentrations with rapid read-out, achieving single-molecule sensitivity and multiplexed analysis in complex samples.
Implementation Method 1
a motor protein is bound to the carrier such that it can control the movement of the identifier region within the nanopore
Implementation Method 2
taking one or more optical or electrical measurements as a carrier moves within the nanopore to characterise the identifier region and to determine whether or not the molecule is bound to the molecule-binding region
Data Source
AI summary
A method for detecting multiple molecules in a sample, the method comprising: (a) contacting the sample with a carrier and a nanopore, wherein the carrier comprises a single-stranded leader, an identifier region and a molecule-binding region specific for a molecule to be detected, and wherein a motor protein is bound to the carrier such that it can control the movement of the identifier region within the nanopore; (b) taking one or more optical or electrical measurements as a carrier moves within the nanopore to characterise the identifier region and to determine whether or not the molecule is bound to the molecule-binding region.