Researchers at Harvard University have developed a semiconductor chip that can synthesize 64 different DNA sequences in parallel using electric currents and a water-based enzymatic process, potentially offering an alternative to conventional DNA manufacturing methods.

The chip uses localized electrical control to trigger DNA synthesis at selected sites on its surface. The team says the approach avoids the solvent-heavy phosphoramidite chemistry widely used to produce synthetic DNA today.

Synthetic DNA is a key tool in modern biotechnology, supporting applications ranging from diagnostics and genome engineering to cancer research. While enzymatic DNA synthesis has emerged as a more environmentally friendly alternative, it has struggled to match the scale of conventional methods.

According to the researchers, enzymatic approaches have so far been limited to producing about a dozen DNA sequences simultaneously. In the new study, the chip generated 64 distinct DNA sequences in parallel, with each sequence reaching up to 39 nucleotides in length.

Electricity guides DNA

DNA synthesis occurs one nucleotide at a time. After each addition, a temporary blocking group must be removed before the next nucleotide can be attached.

To control this process, the Harvard team designed a chip with 64 synthesis sites. Each site contains two concentric ring electrodes surrounding DNA strands anchored at the center.

When activated, the inner electrode generates protons that lower the pH around a selected DNA strand. This acidic environment enables enzymatic DNA growth. At the same time, the outer electrode consumes diffusing protons, preventing the low-pH region from spreading to neighboring sites.

By repeating this process across selected locations during each synthesis cycle, the chip can build many different DNA sequences simultaneously.

The work builds on a semiconductor platform originally developed for neuroscience applications.

“A defining feature of the chip was precision current injection, which we used to permeabilize neuronal membranes for intracellular access,” said Donhee Ham, John A. and Elizabeth S. Armstrong Professor of Engineering and Applied Sciences at Harvard.

“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.”

Data storage potential

Beyond biological applications, the researchers explored whether the technology could support DNA-based data storage.

Using the 64 synthesized DNA sequences, the team encoded a 169-byte text message, demonstrating the platform’s potential for storing digital information in DNA molecules.

The researchers believe a water-based synthesis approach could become increasingly important if DNA production scales dramatically in the future.

“DNA data storage asks DNA synthesis to operate at a scale far beyond today’s needs,” said Woo-Bin Jung, co-first author of the study.

“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.”

The team also attempted to increase the density of synthesis sites on the chip. While those experiments failed, they revealed that the main limitation came from the chemistry used to remove blocking groups rather than from the chip’s electronic architecture.

“The chip did what we asked it to do: it localized low pH at selected sites,” said Han Sae Jung, co-first author of the study. “The limitation came from the deprotection chemistry, not from the silicon.”

The study was published in Nature Electronics.

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