According to Eric Niiler, scientists have long wanted to build motors, transistors and switches at the molecular level with hopes of one day being able to help fight diseases or do amazing mini-feats of engineering. A group of California researchers say they’ve made a big step toward that effort in an experiment that linked 74 DNA molecules together to perform a square-root computation.
It’s the largest biochemical circuit ever made, and could lead to new ways of building tiny diagnostic tests and new biosensors, according to Erik Winfree, co-author and professor of computer science, computation and neural systems, and bioengineering at the California Institute of Technology.
“When the first transistor was built, they could do one,” Winfree said. “Then they hooked together 10 into a circuit, now we are at millions. Some information technologies have this scaling property. That’s what we are looking for at the biochemical level.”
To build these biochemical circuits, Winfree and postdoctoral student Lulu Qian used strands of DNA to make a series of “see-saw gates” that produce on or off signals when responding to contact with another molecule. In a computer, these gates are made with electronic transistors, which are wired together to form circuits on a silicon chip. Winfree and Qian built their biochemical transistor in a test tube. Their work is being published in today’s edition of the journal Science.
“Our seesaw reaction using DNA is somewhat analogous to a transistor, except here the signals are concentrations of molecules,” Winfree said.
The strands of DNA formed a circuit that can compute the square root of a number up to 15, and round it to the nearest integer. Even though the molecular calculator worked, it took a long time. Because different kinds of chemical molecules interfered with the DNA “seesaw gates,” each individual bio-circuit took 30 to 60 minutes to complete, and the whole operation took more than 10 hours.
Winfree says the goal isn’t speed but accuracy, and developing the right kind of structure so different kinds of biochemical circuits can follow.
Winfree and his colleagues first built this kind of circuit back in 2006. But he was able to figure out a way to make a simpler connection so the whole process could be expanded successfully. Other experts in the field praised the experiment and said it has given them a roadmap for their work.
“(Winfree) and others have created a field that has enormous potential,” said Andy Ellington, professor of biochemistry at the University of Texas.
Ellington’s lab is developing a diagnostic test for malaria so that doctors will be able to identify patients in the jungle rather than bringing samples back to a hospital. The test uses a similar chain of biochemical transistors to perform a blood analysis for the malaria parasite. Ellington said Winfree’s experiment is good news for the field of DNA computation.
“Seeing that it is possible is important,” Ellington said. “It provides design principles for others like myself.”
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