Scientists at Harvard have repurposed silicon chip technology to build DNA sequences faster and cleaner than current industrial methods allow. The breakthrough, published in Nature Electronics, demonstrates that the same electronics used to monitor brain activity can be adapted to synthesize genetic material.
The chip successfully manufactured 64 different DNA strands in parallel, each containing 39 nucleotides. That marks a significant jump from previous enzymatic synthesis attempts, which topped out at around a dozen sequences simultaneously. The achievement opens a path toward decentralized, safer DNA manufacturing that avoids the toxic solvents required by today's dominant production method.
Most synthetic DNA is currently made using phosphoramidite chemistry, a proven but solvent-intensive process that demands specialized industrial facilities. Scientists have long sought an alternative using enzymatic synthesis, which relies on water and mimics how living cells naturally build DNA. The water-based approach is gentler on the environment and could eventually be deployed in smaller, local facilities. Until now, it simply couldn't produce sequences fast enough to compete with conventional methods.
Donhee Ham, the John A. and Elizabeth S. Armstrong Professor of Engineering at Harvard's School of Engineering and Applied Sciences, led the research team. The innovation came partly by accident. Jeffrey Abbott, a former graduate student in Ham's lab, had originally designed the silicon electronics to record electrical signals from neurons. When researchers modified the surface electrodes, they realized the same precision current injection that penetrated cell membranes could control chemical conditions needed for DNA synthesis.
The chip works by assembling DNA one building block at a time. After each nucleotide attaches, a chemical blocker prevents further growth until it's removed. Removing that blocker requires acidic conditions. The Harvard chip uses tiny electrical currents to lower pH only at selected locations across its surface. The device contains 64 synthesis sites, each ringed by concentric electrodes. When activated, the inner electrode generates protons that acidify the local area, allowing DNA to grow. The outer electrode simultaneously removes protons that drift outward, keeping the acidic zone confined to that single spot.
By cycling this process repeatedly, the chip independently constructs 64 unique DNA sequences across its surface, each precisely controlled and spatially isolated from its neighbors.
The Next Frontier: Scale and Chemistry
Researchers tested whether they could push the technology further by placing synthesis sites closer together. The experiment failed, but it revealed something important. The chip itself worked perfectly, accurately localizing low pH exactly where needed. The real bottleneck lay in the chemistry itself.
During the deprotection step, low pH creates intermediate molecules that strip away the blocking groups. These intermediates can diffuse into neighboring synthesis sites, contaminating reactions even though pH remains tightly controlled. Han Sae Jung, a co-first author and Harvard graduate student, noted that the problem belonged to the deprotection chemistry, not the silicon.
"The chip did what we asked it to do: it localized low pH at selected sites," Jung said. "The limitation came from the deprotection chemistry, not from the silicon. That leaves a clear next step for the field: develop a more direct acid-driven deprotection chemistry that can keep pace with the chip."
The research team also demonstrated a potential future application. They used the 64 synthesized sequences to encode a 169-byte text message, hinting at the possibility of DNA data storage. Such storage would require manufacturing DNA at massive scale, but enzymatic synthesis in water could become increasingly attractive as production volumes grow. Lower solvent consumption would substantially reduce the environmental footprint of large-scale DNA manufacturing.
Woo-Bin Jung, now an assistant professor of chemical engineering at Pohang University of Science and Technology, noted that DNA data storage currently demands scale far beyond today's capabilities. "If far more than 64 sequences can be synthesized in parallel, it could offer an environmentally friendly route toward writing DNA at very large scale," he said.
The project involved collaboration among researchers at Harvard, the Broad Institute, DNA Script, and Pohang University. Harvard's Office of Technology Development has filed intellectual property related to the platform. Funding came from the Office of the Director of National Intelligence, the Intelligence Advanced Research Projects Activity, Horizon Europe, and Samsung Research Funding and Incubation Center.
Author Jessica Williams: "This is what happens when you let scientists cross disciplines: brain-recording electronics become DNA-writing machines. The chemistry is now the puzzle piece, and that's exactly where innovation should go next."
Comments