Silicon chips have driven the computing revolution for more than 50 years. Now, researchers are finding new ways to use them in biology, including monitoring large groups of neurons, sequencing DNA, and even manufacturing DNA itself.

A Harvard-led research team has developed a silicon chip that can synthesize 64 different DNA sequences at the same time. The work, published in Nature Electronics, replaces the solvent-heavy chemistry commonly used in custom DNA production with a water-based enzymatic method.

Rather than controlling DNA synthesis with conventional laboratory equipment, the chip uses precisely regulated electric currents to activate chemical reactions at individual locations across its surface. The research was led by Donhee Ham, the John A. and Elizabeth S. Armstrong Professor of Engineering and Applied Sciences at the John A. Paulson School of Engineering and Applied Sciences (SEAS).

A Chip That Writes DNA in Water
Synthetic DNA plays a central role in many areas of modern science and medicine, including diagnostics, genome engineering, and cancer research.

Most synthetic DNA is currently produced through phosphoramidite chemistry. This well-established process can create millions of sequences in parallel, but it relies on hazardous organic solvents and is usually carried out in large, centralized facilities.

Enzymatic DNA synthesis offers a gentler alternative. It takes place in water and more closely resembles the way living cells naturally assemble DNA. In the future, this approach could make DNA-writing devices smaller, safer, and easier to use.

Until now, however, enzymatic methods have lagged far behind conventional chemistry in the number of DNA sequences they can produce simultaneously. Previous systems had created no more than about a dozen sequences at once.

The Harvard team raised that number to 64 distinct sequences, with each one reaching a length of up to 39 nucleotides. The result establishes a new benchmark for parallel enzymatic DNA synthesis.