Big leap forward for DNA computing

Caltech researchers have built the most complex biochemical circuit ever, creating a DNA computer that can calculate square roots.

Previous lab-made biochemical circuits have worked less reliably and predictably when scaled to larger sizes, probably because they need various molecular structures to implement different functions, making large systems more complicated and difficult to debug.

The Caltech approach, however, involves components that are simple, standardized, reliable, and scalable, meaning that even bigger and more complex circuits can be made and still work reliably.

“You can imagine that in the computer industry, you want to make better and better computers,” says senior postdoctoral scholar Lulu Qian.

“This is our effort to do the same. We want to make better and better biochemical circuits that can do more sophisticated tasks, driving molecular devices to act on their environment.”

To build their circuits, the researchers used pieces of DNA to make  logic gates. In a conventional computer, they’re made with electronic transistors, which are wired together to form circuits on a silicon chip.

Biochemical circuits, however, consist of molecules floating in a test tube of salt water. Instead of depending on electrons flowing in and out of transistors, DNA-based logic gates receive and produce molecules as signals. The molecular signals travel from one specific gate to another, connecting the circuit as if they were wires.

The Caltech logic gates are made from pieces of either short, single-stranded DNA or partially double-stranded DNA. The single-stranded DNA molecules act as input and output signals that interact with the partially double-stranded ones.

“The molecules are just floating around in solution, bumping into each other from time to time,” says professor Erik Winfree.

“Occasionally, an incoming strand with the right DNA sequence will zip itself up to one strand while simultaneously unzipping another, releasing it into solution and allowing it to react with yet another strand.”

Because the researchers can encode whatever DNA sequence they want, they have full control over this process.

Qian and Winfree have made several circuits with their approach. The largest — containing 74 different DNA molecules — can compute the square root of any number up to 15, and round down the answer to the nearest integer.

The researchers then monitor the concentrations of output molecules during the calculations to determine the answer – which currently takes about 10 hours. Well, it is an early version.

“Like Moore’s Law for silicon electronics, which says that computers are growing exponentially smaller and more powerful every year, molecular systems developed with DNA nanotechnology have been doubling in size roughly every three years,” says Winfree.

Qian adds, “The dream is that synthetic biochemical circuits will one day achieve complexities comparable to life itself.”