Nucleic Acid Synthesis Device Using Segmented Reaction Chambers
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Solution Overview
Problem
Current methods for synthesizing oligonucleotides are inefficient, costly, and lack scalability, failing to provide high-quality oligonucleotides rapidly and inexpensively for various applications in molecular biology and diagnostics.
Innovation Solution
A device and method for synthesizing polynucleotides on a solid support, utilizing a plurality of features with oligonucleotides having predetermined subunit sequences, allowing for microfluidic communication and controlled temperature to facilitate annealing, chain extension, and ligation reactions, enabling the production of high-quality oligonucleotides with diverse sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional oligonucleotide synthesis methods are used, then oligonucleotides can be produced, but the synthesis is inefficient, costly, and lacks scalability
Solution Approach 1:
The synthesis device is divided into multiple independent reaction chambers arranged in a spatial array, with each chamber capable of performing complete synthesis cycles independently. This segmentation enables parallel processing of multiple oligonucleotide sequences simultaneously, dramatically improving productivity while keeping each individual chamber relatively simple in design
Solution Approach 2:
Each reaction chamber is designed as a universal module capable of performing all necessary synthesis operations (annealing, extension, denaturation, washing) for any oligonucleotide sequence. This multi-functionality allows the same device structure to synthesize diverse polynucleotide products without requiring complex reconfiguration, resolving the contradiction between versatility and device complexity
2Productivity
If rapid oligonucleotide production is achieved, then throughput increases, but cost-effectiveness and quality may compromise
Solution Approach 1:
The device implements continuous cycling through annealing, extension, denaturation, and washing steps in each reaction chamber without interruption. This continuous operation maintains high throughput while ensuring that each synthesis cycle completes fully, preserving oligonucleotide quality. The automated progression through standardized cycles prevents errors that could compromise manufacturing precision
Solution Approach 2:
The device incorporates detection mechanisms to monitor synthesis progress and product quality in real-time. This feedback allows the system to adjust parameters or repeat cycles as needed, ensuring high-fidelity oligonucleotide production even at high throughput. The feedback loop maintains quality standards while enabling rapid production by identifying and correcting issues immediately
3Adaptability or versatility
If diverse polynucleotide sequences are synthesized, then versatility improves, but synthesis cost and complexity increase
Solution Approach 1:
The device uses universal reaction chambers and standardized protocols that can synthesize any oligonucleotide sequence without requiring different hardware configurations. This universality enables diverse sequence synthesis while maintaining cost-effectiveness, as the same inexpensive, modular components are reused across all synthesis tasks rather than requiring specialized equipment for each sequence type
Solution Approach 2:
The device achieves sequence diversity by varying biochemical parameters (primers, nucleotides, temperature cycles) rather than changing physical device components. This approach allows synthesis of diverse polynucleotide sequences using the same hardware platform, keeping manufacturing costs low while maximizing versatility. Parameter changes are inexpensive compared to hardware modifications
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
The solution enhances the accuracy, yield, throughput, and cost-efficiency of nucleic acid synthesis, enabling the rapid production of high-fidelity polynucleotides with desired sequences, addressing the limitations of existing technologies.
Implementation Method 1
The device can include a microfluidic member for providing a droplet to a first spot having a first oligonucleotide having a first predetermined subunit sequence to substantially cover the first spot, and the droplet can include one or more reagents that allow one or more of annealing, denaturing, chain extension reaction, ligation, and digestion reaction
Implementation Method 2
a microfluidic member for providing a droplet to a first spot having a first oligonucleotide
Data Source
AI summary
Disclosed are devices and methods to synthesize polynucleotides and libraries of polynucleotides such as libraries of oligonucleotides. In exemplary embodiments, the device includes a support having a plurality of features. Each feature contains a plurality of oligonucleotides. Within each feature, each of the plurality of oligonucleotides includes an identical predetermined subunit sequence of X nucleosides and a degenerate sequence of Y nucleosides. A predetermined combination of a subset of the features can be used to produce a polynucleotide having a predetermined sequence of Z nucleosides.