DNA Origami Nanopore for Wide-Channel Biomolecule Sensing
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Solution Overview
Problem
Current nanopores fail to meet the criteria of being sufficiently wide, structurally defined, and adaptable for sensing large biomolecules like folded proteins, and are not compatible with hydrophobic membrane formats used in portable analytical devices.
Innovation Solution
A membrane-spanning nanopore composed of at least one scaffold polynucleotide strand, a plurality of staple polynucleotide strands, and hydrophobically-modified polynucleotide strands, with a central channel width of at least 5 nm, formed via DNA origami techniques, allowing for tailored dimensions and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If conventional nanopores are used, then the channel width is limited, but the ability to sense large biomolecules like folded proteins is insufficient
Solution Approach 1:
The nanopore is constructed from multiple discrete DNA components (scaffold strand and staple strands) that self-assemble to form a segmented structure with a wide central channel. This segmentation allows the channel width to be independently optimized for large biomolecule passage while maintaining structural integrity through the modular DNA component architecture.
Solution Approach 2:
The patent utilizes DNA origami techniques to precisely control and adjust the geometric parameters of the nanopore, particularly the channel width. By modifying the DNA sequence design and staple strand configurations, the channel dimensions can be tuned to achieve optimal width for sensing folded proteins while maintaining structural definition and stability.
2Length of moving object
If nanopores are made wider to accommodate large biomolecules, then the structural definition and stability may be compromised
Solution Approach 1:
The nanopore employs a composite DNA structure where scaffold strands provide the overall framework and staple strands reinforce specific regions. This composite architecture distributes mechanical stress and maintains structural definition even as channel width increases, preventing collapse or deformation of the pore structure.
Solution Approach 2:
The patent transitions from considering only channel width (one dimension) to incorporating vertical wall thickness and lateral reinforcement (additional dimensions) in the nanopore design. The DNA double-helix structure provides vertical reinforcement while staple strands add lateral structural support, creating a three-dimensionally optimized structure that maintains stability at wider dimensions.
3Manufacturing precision
If nanopores are designed for specific biomolecule sizes, then the adaptability for different biomolecule sizes is reduced
Solution Approach 1:
The nanopore design incorporates adjustable parameters through DNA sequence modification, allowing the same fundamental structure to be dynamically reconfigured for different channel widths. This dynamic design approach enables the nanopore to be adapted for sensing various biomolecule sizes by simply adjusting the DNA staple strand configurations rather than requiring completely different pore structures.
Solution Approach 2:
The patent creates a universal nanopore platform based on DNA origami that can serve multiple sensing applications. The modular DNA component system allows a single design framework to be applied across different biomolecule detection scenarios by adjusting specific sequence parameters, achieving multi-functionality without sacrificing manufacturing precision.
4Reliability
If traditional nanopore materials are used, then compatibility with hydrophobic membrane formats for portable devices is limited
Solution Approach 1:
The patent modifies the surface properties of the DNA nanopore by controlling its charge distribution and hydrophilicity/hydrophobicity characteristics. By adjusting DNA sequence composition and adding appropriate chemical modifications, the nanopore achieves optimal interaction with hydrophobic membrane formats, enabling reliable integration into portable analytical devices while maintaining ease of manufacture through standardized DNA synthesis protocols.
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 nanopore enables effective sensing of large biomolecules by providing a stable, wide channel for ion flow measurement, enhancing sensitivity and adaptability for different biomolecule sizes, and can be integrated into both biological and synthetic membranes.
Implementation Method 1
at least one hydrophobically-modified polynucleotide strand, wherein the hydrophobically-modified polynucleotide strand comprises a polynucleotide strand and a hydrophobic moiety
Implementation Method 2
each of the plurality of staple polynucleotide strands hybridises to the or each at least one scaffold polynucleotide strand to form the three-dimensional structure of the membrane-spanning nanopore
Data Source
AI summary
A membrane-spanning nanopore is provided that comprises:i. at least one scaffold polynucleotide strand;ii. a plurality of staple polynucleotide strands; andiii. at least one hydrophobically-modified polynucleotide strand, wherein the at least one hydrophobically-modified polynucleotide strand comprises a polynucleotide strand and a hydrophobic moiety; wherein each of the plurality of staple polynucleotide strands hybridises to the at least one scaffold polynucleotide strand to form the three-dimensional structure of the membrane-spanning nanopore, and wherein the at least one hydrophobically-modified polynucleotide strand hybridises to a portion of the at least one scaffold polynucleotide strand, the membrane-spanning nanopore defining a central channel with a minimum internal width of at least about 5 nm.