Harvard Scientists Repurpose Silicon Chips for Parallel Enzymatic DNA Synthesis

Researchers at Harvard University have developed a silicon chip capable of synthesizing 64 unique DNA sequences simultaneously, representing a major expansion of semiconductor utility into biotechnology. This water-based enzymatic approach replaces traditional, solvent-intensive chemical methods with localized electrical currents to control molecular assembly. The breakthrough offers a more sustainable and scalable path for synthetic biology, diagnostics, and the emerging field of DNA-based data storage.

Led by Professor Donhee Ham at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), the research team successfully synthesized 64 different DNA sequences in parallel, each 39 nucleotides long. The device utilizes a silicon chip surface featuring 64 synthesis sites, each equipped with concentric ring electrodes. By applying precise electrical currents, the inner electrode generates protons to lower the local pH, triggering the enzymatic reactions necessary to add nucleotides to a DNA strand. Simultaneously, the outer electrode removes protons to prevent them from spreading, ensuring the acidic environment remains confined to a single site. This method marks a significant milestone, as previous enzymatic synthesis attempts were limited to roughly a dozen sequences at once.

The technology behind the chip was originally engineered by Jeffrey Abbott for recording electrical activity within large populations of neurons. The researchers realized that the precision current injection used to permeabilize neuronal membranes could be adapted to control the chemical conditions required for DNA synthesis. By redesigning the surface electrodes into ring pairs, the team transitioned the hardware from a biological sensor to a molecular manufacturer. To demonstrate the chip's practical potential for the computing sector, the researchers used the 64 synthesized sequences to encode a 169-byte text, illustrating a viable path toward large-scale DNA data storage that avoids the environmental hazards of organic solvents used in conventional phosphoramidite chemistry.

Despite the success of the 64-site chip, the team encountered challenges when attempting to further increase the density of synthesis sites. While the silicon hardware accurately localized the low pH levels, the chemical intermediates involved in the deprotection process drifted into neighboring sites, causing cross-contamination. This finding suggests that the current bottleneck for scaling DNA writing on silicon is not the semiconductor architecture itself, but rather the underlying chemistry. The study, which involved collaboration with the Broad Institute, DNA Script, and Samsung Electronics, concludes that developing more direct acid-driven deprotection chemistry will be the next critical step in leveraging silicon's massive scaling potential for biotechnology applications.