Continuous Nucleic Acid Synthesis Apparatus
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Solution Overview
Problem
Current methods for synthesizing oligonucleotides are limited by batch process constraints, which restrict the length of oligonucleotides that can be produced and hinder the ability to efficiently manufacture longer sequences.
Innovation Solution
A continuous process and device for nucleic acid synthesis that includes multiple units for deprotection, coupling, oxidation/thiolation, and washing, allowing for simultaneous processing of multiple reaction vessels through a conveyor system, thereby overcoming batch process limitations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If batch process synthesis is used, then equipment complexity is reduced, but oligonucleotide length is limited and productivity is low
Solution Approach 1:
The synthesis system is divided into multiple independent reaction vessels (e.g., 6 vessels) that can be processed simultaneously in a continuous flow manner. Each vessel handles a specific stage of oligonucleotide synthesis, allowing longer sequences to be produced by distributing the synthesis load across multiple segments rather than attempting to synthesize the entire sequence in a single batch reactor.
Solution Approach 2:
Multiple reaction vessels are prepared in advance with different reagents and conditions before the continuous synthesis process begins. This preliminary preparation allows the system to immediately start continuous production without sequential setup, enabling longer oligonucleotide synthesis while maintaining streamlined operations.
2Productivity
If batch process synthesis is used, then device complexity is reduced, but production time increases
Solution Approach 1:
The system implements continuous synthesis where reactants flow continuously through multiple reaction vessels in sequence. This eliminates the stop-start nature of batch processing, maintaining continuous productive action throughout the synthesis process. Multiple vessels operate simultaneously at different stages, dramatically reducing total production time for long oligonucleotides compared to traditional batch methods.
Solution Approach 2:
The system uses dynamic control of fluid flow rates and timing to optimize the synthesis process. Flow rates are adjusted to match reaction kinetics, and the continuous movement of reactants through multiple vessels allows real-time optimization of production speed while maintaining product quality.
3Manufacturing precision
If continuous processing with multiple vessels is used, then oligonucleotide length and productivity are improved, but device complexity and mass transfer requirements increase
Solution Approach 1:
The system employs hydraulic or pneumatic actuation to control fluid flow through the multiple reaction vessels. This allows precise control of reactant delivery and mixing without complex mechanical pumping systems, achieving efficient mass transfer while keeping the overall device architecture relatively simple and maintainable.
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 the synthesis of longer oligonucleotides and polypeptides by allowing for continuous processing, improving mass transfer, and reducing production time and costs while maintaining high quality and yield.
Implementation Method 1
A deprotectant, acting through a detritylation mechanism, is added to remove the DMT from the nucleoside
Implementation Method 2
The phosphorus in the amidites bonds with the oxygen in the hydroxyl, thus providing support-bound nucleotides
Implementation Method 3
An oxidizing agent can then be added to convert the trivalent phosphorous to pentavalent
Data Source
AI summary
A method and apparatus for nucleic acid synthesis. The method employs a device including at least one deprotection unit to carry out a step of deprotection, at least one coupling unit to carry out a step of coupling, at least one oxidation/thiolation unit to carry out a step of oxidation or thiolation, at least one capping unit to carry out a step of capping, and at least one washing unit to carry out a step of washing. A plurality of reaction vessels for nucleic acid synthesis are moved to the units in accord with a synthesis scheme for a desired nucleic acid sequence and at least two reaction vessels are simultaneously acted upon at several of the units in series.