Nanopore Biosynthesis via Electrochemical Deprotection
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Solution Overview
Problem
Current biosynthesis systems are limited by speed, flexibility, cost, and form factor, and lack efficient use of multi-channel nanofluidic arrays for high-throughput biomolecule synthesis, with a need for plug-and-play capability and scalability.
Innovation Solution
The development of nanopore-based biosynthesis systems using 2D or 3D nanofluidic arrays with independently addressable electrodes and electrolyte solutions, where primers are coupled to nanopore channels, and voltage is applied to produce acids for removing protecting groups and coupling nucleotides, enabling efficient synthesis of oligonucleotides through repeated cycles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional biosynthesis systems are used, then synthesis can be performed, but speed, flexibility, cost, and form factor are limited
Solution Approach 1:
The biosynthesis system is segmented into multiple independent nanopore channels arranged in arrays, where each channel can perform synthesis reactions independently. This segmentation enables parallel processing of multiple biomolecule synthesis reactions simultaneously, dramatically increasing overall productivity while maintaining manageable device complexity through modular architecture
Solution Approach 2:
The invention transitions from conventional two-dimensional microarray formats to three-dimensional nanofluidic arrays with vertically stacked nanopore channels. This dimensional change increases the density of reaction channels per unit area, enabling higher throughput synthesis while reducing the physical footprint and improving reagent utilization efficiency
2Productivity
If multi-channel nanofluidic arrays are used, then throughput is improved, but manufacturing cost and form factor increase
Solution Approach 1:
The nanopore channel structure serves multiple functions simultaneously: it acts as a reaction chamber for biosynthesis, provides fluidic pathways for reagent delivery, enables electrical addressing for individual channel control, and facilitates product collection. This multi-functionality reduces the need for separate components, simplifying manufacturing and reducing overall system cost while maintaining high throughput
Solution Approach 2:
The invention merges the reaction chamber, fluidic network, and electrode integration into a unified nanopore array structure. By combining these previously separate system elements into a single integrated platform, manufacturing steps are reduced and assembly complexity is minimized, thereby lowering production costs while achieving high-throughput parallel synthesis
3Productivity
If larger systems are used, then synthesis capacity increases, but form factor and sample/reagent requirements increase
Solution Approach 1:
The invention utilizes porous membrane structures containing multiple nanopore channels to provide large synthesis capacity within a compact form factor. The porous architecture maximizes the surface area and channel density within a small volume, enabling high-throughput parallel synthesis without requiring large system size or excessive sample and reagent volumes
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 rapid, flexible, and cost-effective synthesis of biomolecules with improved control and scalability, reducing the system size and sample/reagent requirements, while minimizing manufacturing costs and form factor.
Implementation Method 1
applying a voltage to an electrode of the plurality of electrodes that corresponds to the nanopore channel to produce an acid from the electrolyte solution at the electrode
Data Source
AI summary
A method of synthesizing an oligonucleotide using a nanofluidic device including a plurality of nanopore channels, a plurality of electrodes, and an electrolyte solution, includes coupling a primer to an inner wall of a nanopore channel of the plurality of nanopore channels, the primer having a protecting group. The method also includes applying a voltage to an electrode of the plurality of electrodes that corresponds to the nanopore channel to produce an acid from the electrolyte solution at the electrode. The electrode includes an anode and a cathode disposed at opposite sides of the nanopore channel. The method further includes the acid removing the protecting group from the primer. Moreover, the method includes coupling a nucleotide to the primer with the protecting group removed to form an intermediate product. In addition, the method includes repeating the steps on the intermediate product until the oligonucleotide is synthesized.