An international team of scientists has transformed a conventional silicon chip into a miniature DNA synthesis platform, paving the way for faster, cleaner, and more sustainable biotechnology applications.
Developed by researchers led by Harvard University and reported in Nature Electronics, the new technology uses electricity and water instead of the hazardous organic solvents required by conventional DNA synthesis methods. The chip can simultaneously produce 64 different DNA sequences, setting a new benchmark for enzyme-based DNA manufacturing.
A greener way to manufacture DNA
Synthetic DNA is an essential tool in modern medicine, genetic engineering, molecular diagnostics, and cancer research. Today, most synthetic DNA is produced using phosphoramidite chemistry, a highly reliable technique that depends on large volumes of organic solvents and centralized manufacturing facilities.
The newly developed system replaces this process with an enzyme driven reaction carried out entirely in water, closely mimicking the way living cells naturally build DNA. The researchers believe this approach could eventually enable compact, safer, and environmentally friendly DNA synthesizers.
How the chip “writes” DNA
DNA synthesis proceeds by adding one nucleotide at a time. Before each new nucleotide can be incorporated, a temporary protective chemical group must be removed through a process known as deprotection, which requires a localized acidic environment.
The silicon chip achieves this with remarkable precision using microscopic electrodes. Each of its 64 DNA synthesis sites is surrounded by two concentric ring-shaped electrodes. When activated, the inner electrode generates protons that lower the pH only around the growing DNA strand, allowing the next nucleotide to be added.
At the same time, the outer electrode removes excess protons before they spread to neighboring sites, ensuring that each DNA sequence grows independently. By selectively activating different locations during successive synthesis cycles, the chip can simultaneously assemble dozens of unique DNA sequences.
From brain research to DNA engineering
Interestingly, the chip was not originally designed for DNA synthesis. It was first developed to record electrical activity from thousands of neurons simultaneously and map complex neural connections.
The researchers realized that the same precision electronics could be repurposed to control chemical reactions at the molecular level by redesigning the chip’s electrode architecture.
“The defining feature of the chip was its ability to inject electrical current with exceptional precision. We wondered whether that capability could be redirected from neurons to DNA molecules by generating localized acidic environments for DNA synthesis and it worked,” said Professor Donhee Ham of Harvard’s John A. Paulson School of Engineering and Applied Sciences.
Applications beyond biotechnology
The platform could support a wide range of future applications, including synthetic biology, molecular diagnostics, gene engineering, and personalized medicine.
As a proof of concept, the researchers also demonstrated DNA based digital storage by encoding a 169-byte text file into the 64 synthesized DNA sequences. Although still an early demonstration, the experiment highlights DNA’s enormous potential as an ultra-high-density data storage medium.
Because large-scale DNA data storage would require massive quantities of synthetic DNA, environmentally sustainable manufacturing technologies such as this one could become increasingly important.
The next challenge
After successfully synthesizing 64 DNA sequences, the team attempted to increase the density of synthesis sites on the chip. While the electronic control system continued to function as intended, the researchers encountered a different limitation—the chemistry itself.
They found that the deprotection reaction generates intermediate molecules capable of diffusing into neighboring synthesis sites, causing unintended reactions even though the acidic regions remain tightly confined.
“The chip performed exactly as designed. The remaining limitation lies not in silicon electronics but in the chemistry of deprotection. Developing a more direct chemical strategy will be the key to unlocking the platform’s full potential,” said Han Sae Jung, one of the study’s authors.