Carrier Molecule Nanopore Analyte Detection
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Solution Overview
Problem
Current methods for detecting ultra-small biomarker concentrations in complex clinical samples face challenges such as high translocation speeds of molecules through nanopores, resulting in weak signals and low signal-to-noise ratios, and difficulties in differentiating between similar protein signals, as well as issues with linear DNA carriers forming knots and kinks that cause false positives.
Innovation Solution
A carrier molecule with a molecular frame that defines a central void and a binding moiety specific for the target analyte, where the binding moiety is positioned to allow the analyte to bind within the void, enabling detection through a change in the ion current signature from a double peak to a single peak upon analyte binding, utilizing a nanopore for translocation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If linear DNA carriers are used to host the target molecule, then the mass of the carrier is increased and translocation speed is reduced, but the carriers are prone to forming knots and kinks which provide false positive signals
Solution Approach 1:
The linear DNA carrier is segmented into a closed circular structure by joining its ends, eliminating the free ends that can form knots and kinks. This topological transformation maintains the mass increase benefit while removing the harmful structural defects that cause false positives.
Solution Approach 2:
The invention uses a composite structure combining DNA with protein components to form a stable carrier complex. This composite approach provides structural rigidity that prevents knotting and kinking while maintaining the ability to host target molecules and modulate translocation signals.
2Productivity
If the diameter of the nanopore is larger than the size of the molecule, then translocation occurs, but the translocation speed is high resulting in weak signals and low signal-to-noise ratio
Solution Approach 1:
The invention changes the physical parameters of the carrier molecule by increasing its mass through DNA hosting and optimizing its size relative to the nanopore. This creates an optimal translocation speed range that generates strong, distinguishable signals while maintaining reasonable throughput.
Solution Approach 2:
The carrier molecule's translocation dynamics are optimized by adjusting its mass and interaction properties with the nanopore. The DNA-hosted target complex translocates at a controlled speed that balances signal strength with detection throughput, creating optimal measurement conditions.
3Quantity of substance
If ensemble-averaging immunoassays are used, then detection of biomarkers is achieved, but individual immuno-interactions cannot be identified and only manifest as an ensemble-averaged signal
Solution Approach 1:
The invention extracts the target molecule from the complex mixture and isolates it on an individual carrier molecule. This single-entity approach allows observation of individual binding events rather than ensemble averaging, preserving information about each specific interaction while maintaining detection capability.
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 allows for the reliable detection and quantification of target analytes by modulating the ion current signal, overcoming issues of false positives and signal differentiation, and providing clear evidence of analyte binding, even at low concentrations.
Implementation Method 1
a binding moiety which is specific for the target analyte, wherein the binding moiety is bound to the frame and positioned such that the target analyte, when bound to the binding moiety, is located in the central void
Implementation Method 2
the use of nanopores, where a voltage is applied across the nanopore and pulses in the time-varying electrochemical current, for detecting individual proteins
Data Source
AI summary
A carrier molecule for the detection of a target analyte comprises a molecular frame which defines a central void, and a binding moiety which is specific for the target analyte. The binding moiety is bound to the frame and positioned such that the target analyte, when bound to the binding moiety, is located in the central void. The carrier molecule finds use in the detection and/or quantification of target analytes in a sample.