Harvard scientists have constructed a silicon chip that writes DNA utilizing electrical energy and water, pointing towards a cleaner future for DNA manufacturing and biotechnology.
Silicon chips have pushed the computing revolution for greater than 50 years. Now, researchers are discovering new methods to make use of them in biology, together with monitoring massive teams of neurons, sequencing DNA, and even manufacturing DNA itself.
A Harvard-led analysis crew has developed a silicon chip that may synthesize 64 completely different DNA sequences on the identical time. The work, printed in Nature Electronics, replaces the solvent-heavy chemistry generally utilized in customized DNA manufacturing with a water-based enzymatic methodology.
Rather than controlling DNA synthesis with typical laboratory gear, the chip makes use of exactly regulated electrical currents to activate chemical reactions at particular person places throughout its floor. The analysis was led by Donhee Ham, the John A. and Elizabeth S. Armstrong Professor of Engineering and Applied Sciences on the John A. Paulson School of Engineering and Applied Sciences (SEAS).
A Chip That Writes DNA in Water
Synthetic DNA performs a central position in lots of areas of contemporary science and drugs, together with diagnostics, genome engineering, and most cancers analysis.
Most artificial DNA is presently produced by phosphoramidite chemistry. This well-established course of can create thousands and thousands of sequences in parallel, however it depends on hazardous natural solvents and is often carried out in massive, centralized services.
Enzymatic DNA synthesis affords a gentler various. It takes place in water and extra carefully resembles the way in which dwelling cells naturally assemble DNA. In the longer term, this method might make DNA-writing gadgets smaller, safer, and simpler to make use of.
Until now, nevertheless, enzymatic strategies have lagged far behind typical chemistry within the variety of DNA sequences they will produce concurrently. Previous methods had created not more than about a dozen sequences directly.
The Harvard crew raised that quantity to 64 distinct sequences, with every one reaching a size of as much as 39 nucleotides. The outcome establishes a new benchmark for parallel enzymatic DNA synthesis.
How the Chip Controls DNA Growth
DNA is constructed one nucleotide at a time. After every nucleotide is added, a short-term blocking group prevents the strand from persevering with to develop. Before the following nucleotide may be connected, that blocking group should be eliminated.
This elimination course of is called deprotection. In water, it may be initiated by creating an acidic atmosphere with a low pH.
The problem in parallel DNA synthesis is controlling precisely the place and when that acidity seems. During every cycle, solely the websites which can be prepared for the following nucleotide ought to expertise a drop in pH.
The Harvard chip solves this downside utilizing electrical energy. Its floor incorporates 64 DNA synthesis websites, every geared up with two concentric ring electrodes surrounding DNA strands mounted on the heart.
When a specific website must obtain a nucleotide, the chip sends present into the interior ring. This produces protons and lowers the pH instantly across the DNA strands, permitting enzymatic development to proceed.
At the identical time, the outer ring attracts present in the other way and consumes protons that start to unfold away from the location. This prevents the acidic area from reaching neighboring DNA strands.
By activating completely different websites throughout every synthesis cycle, the chip creates a altering sample of low-pH zones. Over repeated cycles, these localized reactions construct 64 separate DNA sequences.
From Recording Neurons to Manufacturing DNA
The silicon chip was initially developed in Ham’s laboratory by former PhD scholar Jeffrey Abbott for large-scale intracellular recording from neurons.
Researchers initially used the system to document exercise from hundreds of neurons and map a whole lot of synaptic connections. Later variations captured tens of hundreds of connections.
By redesigning the electrodes on the chip’s floor, Ham’s crew tailored the identical digital basis for a wholly completely different function: directing DNA synthesis.
“A defining feature of the chip was precision current injection, which we used to permeabilize neuronal membranes for intracellular access,” Ham stated. “At a certain point, we wondered whether that same current control could be redirected from cells to molecules – replacing the neuron-facing electrodes with ring-electrode pairs that could localize pH for DNA synthesis. It worked.”
A Possible Route to DNA Data Storage
The know-how might ultimately have purposes in artificial biology and medical diagnostics. The researchers additionally demonstrated a extra futuristic chance through the use of the 64 DNA sequences to encode a 169-byte textual content.
That experiment supplied a small-scale instance of DNA-based information storage, a idea through which digital info is saved inside DNA molecules.
DNA storage stays a long-term aim as a result of it could require the manufacturing of huge portions of DNA. Yet that demand might make water-based enzymatic synthesis particularly invaluable.
As the amount of manufactured DNA will increase, the environmental influence of solvents and different chemical waste turns into a larger concern.
“DNA data storage asks DNA synthesis to operate at a scale far beyond today’s needs,” stated Woo-Bin Jung, co-first writer of the research and now an assistant professor of chemical engineering on the Pohang University of Science and Technology (POSTECH), who carried out the work as a postdoctoral researcher in Ham’s lab. “That is why enzymatic synthesis in water can matter. 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.”
Chemistry Becomes the Next Obstacle
After demonstrating 64-sequence synthesis, the researchers wished to find out whether or not the know-how might help much more DNA strands packed into a smaller space.
They fabricated extra carefully spaced synthesis websites on the identical silicon chip, however the denser design didn’t work as supposed. Although the experiment failed, it revealed one of many research’s most vital conclusions.
At first, the researchers have been confused as a result of the electronics have been efficiently maintaining the low-pH areas confined to the chosen websites.
Further experiments confirmed that the issue got here from the deprotection chemistry slightly than the chip.
Low pH doesn’t instantly take away the blocking group from the rising DNA strand. Instead, the acidic situations produce intermediate molecules that perform the deprotection step.
Those molecules can drift into close by synthesis websites. As a outcome, they escape the tightly managed pH zones and trigger reactions to unfold past their supposed boundaries.
“The chip did what we asked it to do: it localized low pH at selected sites,” stated Han Sae Jung, co-first writer of the research and a former graduate scholar and present postdoctoral researcher at Harvard. “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.”
Reference: “Parallel enzymatic DNA synthesis using a semiconductor chip” by Woo-Bin Jung, Han Sae Jung, Jun Wang, Henry Hinton, Seok Joo Kim, Yuchang Zhang, Suyue Chen, Young-Ha Hwang, Maxime Fournier, Manon Boul, Kevin Grosselin, Adrian Horgan, Xavier Godron, Robert Nicol and Donhee Ham, 17 June 2026, Nature Electronics.
DOI: 10.1038/s41928-026-01662-9
The challenge introduced collectively researchers from Harvard, the Broad Institute, DNA Script, and later POSTECH.
Harvard’s Office of Technology Development has filed mental property associated to the platform.
This analysis is predicated upon work supported partly by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), by way of 2019-19081900002, Horizon Europe, Hyperion challenge ID: 101115253, and Samsung Research Funding & Incubation Center for Future Technology of Samsung Electronics beneath Project Number SRFC-IT2402-09.
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