Nanopore Sensor With Synthetic Polymer Membrane
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Solution Overview
Problem
Existing nanopore technologies face challenges in developing a universal sensing strategy for detecting a wide range of target molecules, such as nucleic acids, proteins, and biomolecular complexes, due to the need for adapting pore chemistry and geometry for each class of analytes, and the difficulty in reliably releasing and detecting reporter hairpins.
Innovation Solution
A system comprising a housing with a divider element, structural elements, a chemical layer, and electrode pairs that generate an electric field to facilitate the passage of molecules through an aperture, allowing for the detection of reporter hairpins with varying base pairs or sequence mismatches, and using grayscale photolithography to fabricate stable lipid bilayer membranes that support high-voltage sensing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If a voltage bias is applied across the nanopore to generate ion current, then molecules can be driven through the pore for detection, but the lipid bilayer membrane becomes unstable and ruptures at high voltages
Solution Approach 1:
The patent changes the material parameter of the membrane from natural lipid bilayer to synthetic polymer membrane, which has different mechanical and electrical properties that allow it to withstand higher voltages without rupturing
Solution Approach 2:
The patent uses a composite structure combining synthetic polymer membrane with nanopore, creating a material that integrates the benefits of both components - the durability and voltage resistance of synthetic polymers with the selective transport capability of nanopores
2Measurement precision
If the pore chemistry and geometry are adapted for each class of analytes, then detection accuracy is improved, but the device complexity and assay development time increase
Solution Approach 1:
The patent makes the nanopore system universal by using a synthetic polymer membrane that can detect multiple classes of analytes (nucleic acids, proteins, metabolites, drugs) without requiring pore adaptation, allowing a single pore geometry to serve multiple detection functions
3Speed
If high bandwidth measurement is used to detect short nucleic acids, then detection speed is improved, but the system requires very high bandwidth electronics that increase complexity
Solution Approach 1:
The patent changes the timescale parameter by using synthetic polymer membranes that allow longer observation times for molecule translocation, enabling detection of fast-translocating short nucleic acids at lower bandwidths through extended measurement duration
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 the discrimination of different hairpin molecules based on their electrical signatures, achieving reliable detection and multiplexing capabilities, even at nanomolar concentrations, with improved membrane stability and voltage endurance.
Implementation Method 1
When energized, the electrode pair generates an electric field at a level sufficient to cause the molecules to pass from the first chamber via the aperture to the second chamber
Implementation Method 2
The sensor is configured to sense the molecule as it passes through the aperture
Data Source
AI summary
An apparatus is provided for sensing a molecule in a sample. The apparatus utilizes an electric field to draw molecules from a first chamber through an aperture, defined by a chemical layer, into a second chamber. The apparatus can detect a DNA molecule with, for example, 4, 5, or 6 unique base pairs. As molecules pass through the aperture, a sensor detects or measures a change in an electric parameter used to generate the electric field, thereafter translating the change in the electric parameter into information about the molecule. A divider element separates the first and second chambers and supports a chemical layer defining the aperture. The apparatus enables detection or measurement of molecules over prolonged time at a higher electric field strength than other nanopores, due to a combination of the shape of the divider, structural elements thereon, and thickness of the chemical layer at the aperture.