Patterned Silane Surface for Low Error Oligonucleic Acid Synthesis
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Solution Overview
Problem
Current methods for chemical gene synthesis face challenges with scalability, automation, speed, accuracy, and cost, particularly in achieving high fidelity and low error rates for synthesizing long oligonucleic acids.
Innovation Solution
The development of a surface preparation method using silicon dioxide structures with specific silane molecules to create patterned regions with varying surface energies, allowing for the efficient synthesis of non-identical oligonucleic acids with low error rates by controlling the density of nucleoside-coupling agents and increasing surface area through textured features.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional chemical gene synthesis methods are used, then synthesis can be performed on small scale, but scalability and productivity are limited
Solution Approach 1:
The synthesis surface is divided into multiple discrete loci, each capable of independent oligonucleotide synthesis. This segmentation allows parallel synthesis of many different sequences simultaneously, dramatically increasing productivity while maintaining manageable system complexity through modular architecture
Solution Approach 2:
The invention uses identical loci structures repeated across the synthesis surface, where each locus is a copy of the functional design. This copying approach enables scalable parallel synthesis without increasing the complexity of individual locus design, as the same template can be replicated thousands of times
2Productivity
If high density of nucleoside-coupling agents is used, then synthesis efficiency increases, but error rates increase due to crowding
Solution Approach 1:
Each locus is designed with specific local properties including controlled density of nucleoside-coupling agents. The local quality of each locus can be optimized independently to balance synthesis efficiency and error rates, with surrounding regions having different properties to prevent cross-contamination and reduce crowding effects
Solution Approach 2:
The invention optimizes parameters such as the density and type of nucleoside-coupling agents at each locus to achieve optimal synthesis performance. By adjusting these parameters locally rather than using uniform high density throughout, the system maintains high efficiency while reducing error rates associated with molecular crowding
3Ease of manufacture
If uniform surface treatment is applied, then manufacturing is simple, but synthesis accuracy decreases due to lack of controlled regions
Solution Approach 1:
The surface is treated with different molecules in different regions to create loci with specific properties. Regions containing loci have nucleoside-coupling agents for synthesis, while surrounding regions have blocking molecules to prevent unwanted reactions. This local differentiation ensures high synthesis accuracy while using standardized manufacturing processes
Solution Approach 2:
The surface is pre-treated with blocking molecules in regions surrounding the loci before the actual synthesis begins. This preliminary action prevents potential cross-contamination and ensures that only the intended loci regions are active for synthesis, thereby improving accuracy without complicating the manufacturing process
4Productivity
If small scale synthesis is performed, then cost is reduced, but scalability is limited
Solution Approach 1:
The synthesis surface is segmented into multiple loci that can be independently activated and used for synthesis. This segmentation allows the system to scale from small numbers of loci for low-yield applications to thousands of loci for high-yield applications, providing scalability while maintaining cost-effectiveness by only activating the necessary number of loci for each specific 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 the rapid parallel synthesis of oligonucleic acids with reduced error rates and increased yields, facilitating the production of long sequences with high fidelity and scalability.
Implementation Method 1
depositing a first molecule on the surface at a first region, wherein the first molecule binds to the surface; depositing a second molecule on the surface at a second region, wherein the second molecule binds to the surface; and depositing a mixture on the surface at the second region, wherein the mixture comprises the second molecule and a third molecule, wherein the third molecule binds to the surface
Data Source
AI summary
Methods and devices are provided herein for surfaces for de novo nucleic acid synthesis which provide for low error rates. In addition, methods and devices are provided herein for increased nucleic acid mass yield resulting from de novo nucleic acid synthesis.