Harvard scientists turn a silicon chip into a DNA writing machine
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- Donhee Ham's Harvard team unveiled a silicon chip in Nature Electronics that simultaneously synthesizes 64 distinct DNA sequences — each up to 39 nucleotides long — by running tiny electrical currents through concentric ring electrodes that locally lower pH to drive enzymatic DNA building at each of 64 anchored sites.
- The approach replaces phosphoramidite chemistry, the solvent-heavy industry standard, with a water-based enzymatic process that uses the same low-pH deprotection mechanism living cells rely on, sidestepping the hazardous organic solvents and centralized facilities conventional DNA synthesis requires.
- The leap in scale is explicit: prior enzymatic DNA synthesis demonstrations topped out around a dozen sequences at once, so the 64-sequence parallel run is framed in the paper as a new milestone for the field.
- The chip was repurposed, not purpose-built: it originated as silicon electronics for recording electrical activity inside large populations of neurons, and the team only realized the same precision current injection could localize pH for DNA synthesis after redesigning the surface electrodes into ring pairs.
- To prove the data-storage angle, the researchers encoded a 169-byte text across the 64 synthesized sequences — a proof-of-concept the team believes becomes more attractive as production volumes grow, since water-based synthesis could cut the environmental footprint of DNA manufacturing at scale.
- The next bottleneck is chemistry, not silicon: when the team tried packing synthesis sites closer together to scale higher, the pH stayed confined as intended, but intermediate deprotection molecules drifted into neighboring sites and cross-contaminated reactions — a signal that direct acid-driven deprotection chemistry is now the field's clear next step.
- The work was a cross-institution collaboration among Harvard, the Broad Institute, DNA Script, and POSTECH (where co-first author Woo-Bin Jung is now faculty), with funding from IARPA, Horizon Europe's Hyperion project, and Samsung Research.
Why it matters: Synthetic DNA underpins diagnostics, genome engineering, and cancer research, and phosphoramidite synthesis — the only method that scales to millions of sequences — depends on hazardous organic solvents and centralized facilities. By quintupling the prior parallel-sequencing ceiling for water-based enzymatic synthesis to 64, the Harvard chip makes a solvent-free, potentially portable alternative technically credible, though the team itself shows the real scaling wall is now the deprotection chemistry, not the electronics.
