Bioactivated Nanopore Devices with Annular Overhangs
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Solution Overview
Problem
Current nanopore-based sensors face challenges in detecting molecular interactions at the single molecule level due to issues with nanopore size control, non-specific adsorption, and electrostatic interactions, which hinder precise detection and analysis of biomolecules.
Innovation Solution
The development of bioactivated nanopores with an annular overhang formed by sputtering a metal layer, reducing the nanopore diameter to less than 100 nm, and attaching a single probe molecule or multiple molecules within the overhang, allowing for monitoring of ionic current changes for analyte detection, and using an array of such apertures for enhanced sensitivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nanopore size is reduced to increase detection sensitivity, then single molecule detection capability is improved, but non-specific adsorption and electrostatic interactions increase
Solution Approach 1:
The patent applies local quality by creating an annular overhang structure at the nanopore opening with different properties than the bulk membrane. The overhang provides a localized region for probe molecule attachment that spatially separates the detection zone from the bulk flow region, reducing non-specific adsorption while maintaining high detection sensitivity through the confined geometry.
Solution Approach 2:
The patent uses probe molecules as intermediaries attached to the annular overhang. These probe molecules specifically bind to target analytes, mediating the detection process and reducing non-specific interactions between the nanopore surface and analyte molecules. The probe acts as a selective interface between the nanopore structure and the sample.
2Manufacturing precision
If metal layer is sputtered to form annular overhang, then nanopore diameter is reduced for better molecular discrimination, but fabrication complexity increases
Solution Approach 1:
The patent applies preliminary action by first forming the annular overhang structure through metal layer sputtering before attaching the probe molecules. This pre-formed structure provides a controlled platform for subsequent biochemical functionalization, enabling precise nanopore diameter control to be established before the more sensitive probe attachment step.
Solution Approach 2:
The patent uses composite materials by combining a metal layer (e.g., gold) with the membrane material to form the annular overhang. This composite structure provides both the mechanical stability of the metal and the biochemical functionality needed for probe attachment, achieving precise diameter control while enabling subsequent functionalization.
3Measurement precision
If array of nanopores is used to enhance sensitivity, then detection limit is improved, but signal-to-noise ratio may deteriorate
Solution Approach 1:
The patent merges multiple nanopores into an array structure where each pore contributes to the overall detection signal. By combining the signals from multiple independent nanopores, the detection limit is improved through increased statistical power, while the uniform annular overhang structure ensures consistent probe attachment across all pores, maintaining signal-to-noise ratio.
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 sensitive detection and analysis of molecular interactions with high sensitivity and dynamic range, comparable to ELISA, and is suitable for clinical testing, such as detecting biomarkers like hCG, and can quantify protein biomarkers and detect DNA hybridization.
Implementation Method 1
an annular overhang produced at one end of the aperture, e.g. by sputtering a metal such as gold onto the surface of the support
Implementation Method 2
electrodes and a current sensing device for measuring a change in current through the nanopores upon binding of the analyte
Data Source
AI summary
A nanopore device capable of single molecule detection is described. The nanopores are formed in thin, rigid membranes and modified by a sputtered metal that forms an overhang during application. The overhang causes the pore to be narrower in a certain region, allowing passage of only a single molecule through the pore at a time, or binding to a biomolecule on the pore to be detected by a change in ionic current flow through the nanopore. Embodiments include a silicon nitride membrane formed on a silicon substrate and having a nanopore drilled with a focused ion beam system, followed by gold sputtering onto the membrane. Devices are formed with one or more nanopores and chambers having electrodes on either side of the nanopore.