Horizontal Nanochannel Architecture for Nanopore Sequencing
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Solution Overview
Problem
Current polynucleotide sequencing techniques face challenges in efficiently and accurately determining the sequence of biopolymers due to limitations in controlling and measuring the electrical currents through nanopores, particularly in maintaining ion and fluid flow without ion depletion and complex manufacturing processes.
Innovation Solution
A nanopore sequencing device with a horizontal architecture is developed, featuring a middle well with a sensing electrode, a cis well, and a trans well, where the nanochannel is formed on the substrate surface without through-holes, allowing for precise control of fluidic and electric resistance, and integration of active electronics to regulate flow, enabling efficient sequencing by varying electrical resistance in response to nucleotides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a vertical through-hole nanochannel architecture is used, then fluidic connection between wells is achieved, but manufacturing complexity increases and ion depletion occurs
Solution Approach 1:
The patent inverts the traditional vertical through-hole nanochannel architecture to a horizontal surface-level architecture. Instead of creating deep vertical channels through the substrate, the nanochannels are formed horizontally on the surface, connecting cis, middle, and trans wells laterally. This inversion eliminates the need for complex deep etching and through-hole fabrication while maintaining fluidic connectivity, thereby reducing manufacturing complexity and preventing ion depletion issues associated with vertical through-holes.
Solution Approach 2:
The patent transitions from a vertical (depth-oriented) nanochannel configuration to a horizontal (surface-oriented) configuration. By changing the dimensionality from vertical through-holes to horizontal surface channels, the design avoids the manufacturing challenges of deep substrate penetration while maintaining effective fluidic and ionic connectivity between wells.
2Measurement precision
If nanopore sequencing is performed, then polynucleotide sequence determination is achieved, but control and measurement of electrical currents becomes difficult
Solution Approach 1:
The patent introduces a middle well as an intermediary chamber between the cis well and trans well. This middle well contains a sensing electrode that serves as an intermediary measurement point, allowing precise monitoring and control of electrical currents during polynucleotide translocation. The intermediary well enables better signal detection and current control compared to direct cis-to-trans measurements, thereby improving sequence determination accuracy while facilitating electrical current management.
Solution Approach 2:
The patent segments the traditional two-well architecture into three separate wells (cis, middle, trans). This segmentation allows the middle well to function as a dedicated sensing and control zone, separating the measurement function from the fluid transport function. The segmented architecture enables independent optimization of each well's function, improving both measurement precision and electrical current control.
3Ease of manufacture
If horizontal nanochannel architecture is used, then manufacturing complexity is reduced and ion concentrations are maintained, but device structure becomes different from conventional designs
Solution Approach 1:
The patent inverts the conventional vertical nanochannel design to a horizontal configuration. This inversion simplifies manufacturing by eliminating the need for complex deep etching and through-hole formation, while the resulting horizontal surface-level structure provides adequate fluidic connectivity without requiring intricate three-dimensional arrangements.
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 enhances the accuracy and efficiency of sequencing by maintaining consistent ion concentrations, reducing manufacturing complexity, and allowing for precise control of nanochannel resistance, thereby improving the robustness and reproducibility of the sequencing process.
Implementation Method 1
a nanopore, which can provide a path for an ionic electrical current
Implementation Method 2
a nanochannel fluidically connecting the middle well and the trans well
Implementation Method 3
at least one sensing electrode on a surface of the dielectric layer... enabling efficient sequencing by varying electrical resistance in response to nucleotides
Data Source
AI summary
Devices for sequencing biopolymers, methods of manufacturing the devices, and methods of using the devices are disclosed. In one example, such a device has a nanopore and a horizontal nanochannel. In some embodiments, the horizontal nanochannel may take a tortuous path. In some embodiments, such a device includes gas or air bubble generators or pressure pulse generators to block or unblock the horizontal nanochannel.