Harvard scientists turn a silicon chip into a DNA writing machine

Silicon chips have been the foundation of modern computing for decades. Now, researchers are giving them an entirely new role in biotechnology.

Silicon chips have been the foundation of modern computing for decades. Now, researchers are giving them an entirely new role in biotechnology. In addition to processing information, these chips are increasingly being used to study living systems by recording activity from neurons, reading DNA, and now even creating DNA.

In a new study published in Nature Electronics , a Harvard led research team unveiled a silicon chip capable of synthesizing 64 different DNA sequences at the same time. Instead of relying on the solvent intensive chemical process commonly used to manufacture synthetic DNA, the device uses a water based enzymatic approach. Carefully controlled electrical currents trigger DNA building reactions at specific locations across the chip.

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).

Synthetic DNA is essential for many areas of modern science and medicine, including diagnostics, genome engineering, and cancer research. Today, most custom DNA is produced using phosphoramidite chemistry, a well established method that can manufacture millions of DNA sequences in parallel. However, that process depends on hazardous organic solvents and typically requires specialized centralized facilities.

Scientists have been exploring enzymatic DNA synthesis as a gentler alternative because it uses water and more closely resembles the way living cells naturally build DNA. The approach could eventually enable smaller, safer, and more widely available DNA synthesis systems.

Until now, though, enzymatic methods have lagged far behind conventional manufacturing in the number of DNA sequences they can produce simultaneously. Previous demonstrations had been limited to about a dozen sequences at once. The Harvard team's chip successfully synthesized 64 different DNA sequences in parallel, each as long as 39 nucleotides, establishing a new milestone for the technology.

DNA is assembled one nucleotide at a time. After each nucleotide is added, a temporary blocking group prevents additional growth. Before the next nucleotide can be attached, that blocking group must be removed through a process called deprotection, which is triggered by acidic conditions, or low pH, in water.

Producing many different DNA sequences at the same time requires lowering the pH only at selected locations during each synthesis cycle. The Harvard chip accomplishes this using tiny electrical currents.