Addressable Electrodes for Precise Polynucleotide Deprotection
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Solution Overview
Problem
There is a need for high-density, scalable, automated, and highly efficient systems for synthesizing biomolecules, particularly nucleic acids, with precise control over the deprotection process to enhance synthesis accuracy.
Innovation Solution
A method involving the application of voltage pulses to a solvent in contact with protected biomolecules or polynucleotides to achieve controlled deprotection, using devices with addressable solid supports and electrochemically generated reagents, and a configuration of electrodes and cathodes to manage the deprotection process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional chemical deprotection methods are used, then the deprotection process is simple to implement, but the synthesis accuracy and control over the deprotection process are insufficient
Solution Approach 1:
The patent replaces conventional chemical deprotection methods with electrochemical deprotection. Specifically, electrochemical cells with controlled voltage applications generate deprotection reagents (such as formic acid or hydrobromic acid) in situ at the electrode surface, enabling precise temporal and spatial control over the deprotection process while maintaining synthesis accuracy
Solution Approach 2:
The patent employs controlled voltage parameters (magnitude, duration, pulse frequency) to regulate the deprotection process. By adjusting these electrical parameters, the system achieves precise control over reagent generation rates and deprotection timing, thereby improving synthesis accuracy without requiring complex mechanical intervention
2Productivity
If high-density synthesis systems are implemented, then the productivity and output are improved, but the interference between adjacent synthesis sites increases
Solution Approach 1:
The patent divides the synthesis surface into discrete, addressable electrochemical cells or reaction zones. Each cell is independently controlled with its own electrode configuration, allowing deprotection to occur in isolated compartments. This segmentation prevents cross-contamination and interference between adjacent high-density synthesis sites while maintaining high overall productivity
Solution Approach 2:
The patent implements localized deprotection control where electrochemical reagents are generated only at specific electrode locations and times. By applying voltage selectively to individual cells or regions, the system ensures that deprotection occurs only where needed, eliminating harmful interference from neighboring sites while preserving high-density synthesis capacity
3Manufacturing precision
If multi-pulse voltage application is used, then the deprotection control and synthesis accuracy are enhanced, but the total processing time increases
Solution Approach 1:
The patent employs periodic voltage pulsing where multiple short voltage pulses are applied in sequence rather than a single continuous voltage. Each pulse generates a controlled amount of deprotection reagent, and the periodic nature allows for staged deprotection while maintaining precise control. This approach balances improved deprotection control with reasonable processing time by avoiding unnecessarily long continuous voltage application
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 high-density, efficient, and accurate synthesis of biomolecules by precisely controlling the deprotection process, reducing interference and enhancing synthesis efficiency.
Implementation Method 1
an electrochemical cell comprising: a working electrode configured to generate deprotection reagents when a voltage is applied
Implementation Method 2
the deprotection reagent deprotects at least some of the first plurality of polynucleotides in the first region
Data Source
AI summary
Provided herein are compositions, devices, systems and methods for electrochemical synthesis. Further provided are devices comprising addressable electrodes controlling polynucleotide synthesis (deprotection, extension, or cleavage, etc.) The compositions, devices, systems and methods described herein provide improved synthesis, storage, density, and retrieval of biomolecule-based information.