Automated Nucleic Acid Synthesis and Purification System
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Solution Overview
Problem
Current methods for synthesizing and processing nucleic acids at a nano-scale for information processing systems face challenges in achieving high purity and efficient conjugation, which are crucial for applications in disease diagnosis and treatment.
Innovation Solution
A system comprising multiple instruments and computer programs that automate the synthesis, purification, and conjugation of nucleic acids, including peptide nucleic acids, by measuring and optimizing reaction conditions for single base-resolution chromatography, and facilitating the formation of covalent bonds between different biomolecule products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If automated synthesis and purification systems are implemented, then productivity and purity are improved, but device complexity increases
Solution Approach 1:
The automated system is divided into distinct functional modules: synthesis module, purification module (with HPLC system), conjugation module, and quality control module. Each module performs a specific function and can be independently optimized, allowing high productivity through parallel processing while managing complexity through functional decomposition.
Solution Approach 2:
The automated system integrates multiple functions into a single platform that can perform synthesis, purification, conjugation, and quality control operations. The HPLC system serves both purification and analytical functions, while the robotic handling system manages multiple sample types and reaction conditions, reducing the need for separate specialized equipment.
2Manufacturing precision
If high-purity nucleic acid production is achieved through automated purification, then manufacturing precision is improved, but loss of substance increases
Solution Approach 1:
The system incorporates real-time monitoring and feedback control during the HPLC purification process. UV detectors monitor the elution profile, and the system automatically adjusts flow rates and detection parameters to optimize purification while maximizing recovery. Quality control data feeds back into the synthesis and purification parameters for continuous optimization.
Solution Approach 2:
The HPLC purification process uses dynamic parameter changes including gradient elution (changing mobile phase composition over time), variable flow rates, and temperature control to optimize separation. These parameter adjustments allow high purity recovery by precisely controlling the separation conditions to match the specific nucleic acid properties being purified.
3Manufacturing precision
If multiple instruments and automated processes are used, then manufacturing precision and purity are improved, but loss of time increases
Solution Approach 1:
The automated system operates continuously through integrated workflows where synthesis, purification, and conjugation steps proceed without interruption. The HPLC purification runs continuously with automated sample injection and fraction collection, and the robotic system maintains continuous handling of samples and reagents, eliminating idle time between operations while maintaining single-base resolution purity.
Solution Approach 2:
The system performs preliminary actions including pre-equilibration of HPLC columns, pre-warming of reagents, and pre-programming of purification gradients before actual processing begins. Quality control protocols are built into the workflow in advance, allowing verification without stopping the main production stream, thus maintaining high precision while minimizing time loss.
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-purity nucleic acid production with high recovery rates and efficient conjugation, reducing human intervention and optimizing output, thereby enhancing the capability of nano-scale information processing systems for complex disease applications.
Implementation Method 1
subject the synthesized biomolecule product from each reaction to chromatography under conditions suitable for achieving single base-resolution for the synthesized biomolecule product
Implementation Method 2
measure, for each sample, the volume of the sample and/or the concentration of the synthesized biomolecule product
Data Source
AI summary
A fabrication process for producing, annealing, and conjugating nucleic acid molecules is implemented, under the direction of one or more computer programs, on two or more instruments, for carrying out the process. The process can include: (a) synthesizing, on a solid support and in a plurality of reactions, at least one of a nucleic acid and a peptide nucleic acid, and cleaving the synthesized biomolecule product from the support, providing a sample of synthesized biomolecule product from each reaction of the plurality; (b) measuring, for each sample, the volume of the sample and/or the concentration of the product; (c) subjecting the product from each reaction to chromatography under conditions suitable for achieving single-base-resolution for the product, the conditions being a function of the volume and/or concentration measured in (b); and then (d) collecting and pooling, from the chromatography of (c) for each sample, peaks that correspond to the product.