Since its initial development in the 1980s traditional chemical synthesis of DNA has been relatively unchanged despite successes in miniaturization and automation. Because of high error rates in traditional chemical syntheses, longer DNA strands are often created using short oligonucleotide strands that are synthesized individually and then pieced together. This process is laborious, expensive, and slow. While electrochemical approaches for oligonucleotide synthesis offer the potential for lower error rates and longer strand synthesis, the apparatus designs present complications with proton localization and significant cross-talk.
Researchers at the Biodesign Institute of Arizona State University have developed a novel apparatus and electrochemical methods for rapid and efficient oligonucleotide synthesis. This system uses a specially-designed apparatus, with no moving parts, to control the synthesis schemes. A consistent proton concentration is introduced into the apparatus to provide stable step yield with longer sequence synthesis. The nucleotide bases are delivered globally, but are controlled such that only certain strands will allow DNA synthesis to occur. The parameters and surface properties of the apparatus are combined with specific synthesis schemes to optimize the localization of reactions, the purity of the synthesized DNA, as well as the yield of the oligonucleotide synthesis. A 12mer DNA oligomer has been successfully synthesized and verified by hybridization as proof of concept.
This optimized, direct on-chip apparatus and methodology provide for a fast throughput and high-efficiency system that could revolutionize de novo oligonucleotide synthesis.
• Synthetic biology
o Personalized medicine
• DNA storage/computing
• DNA microarrays
Benefits and Advantages
• Stable step yield and synthesis speed even with long sequences
• Spatial resolution of better than 30 µm between individual sites
o This allows device density of ~1000 sites per mm square, or ~100K sites per cm square
o Current efforts focus on getting >1M sites per cm square
• Localized and controlled activation of the chain of reactions of DNA synthesis
• Fast throughput and high efficiency
• No mechanical moving parts are utilized
• Lower cross-talk
• Improved fabrication methods for creating consistent and accurate parameters
For more information about the inventor(s) and their research, please see