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Dream Machine

Just as systems biology aggressively strives to piece together biological networks, the Institute for Systems Biology has pieced together networks of leading scientists. And in perhaps the most intriguing joint effort to date, called the NanoSystems Biology Alliance, the institute is collaborating with leading nanotechnologists at Caltech and medical researchers at the University of California, Los Angeles. The goal is to squeeze many of the highly automated processes used in systems biology onto a one-square-centimeter silicon chip. If the NanoSystems group delivers on its promise, it will create a “nanolab,” a chip that will have the power to outperform entire laboratories. In that systems biology is an approach that prizes technology that is smaller, cheaper, and faster, the nanolab is a dream machine. “It has the possibility of utterly revolutionizing systems biology,” says Hood.

The researchers hope that, given just one drop of blood, the nanolab will separate thousands of cells from each other and, as Aderem says, “interrogate them individually.” The soul of the new machine is an intricate network of microfluidic channels, developed by Caltech physicist Stephen Quake, that range from five to 100 micrometers wide. After being treated with labels that mark specific cell types, the blood sample enters these nanopipes, which can sort, say, macrophages from other white blood cells. Another series of nanopipes equipped with tiny detectors can then identify and separate into various channels the different proteins secreted by the macrophage.

Caltech chemist James Heath has designed one of these detection systems, an array of nanowires that he coats with molecular “hooks” to fish for proteins. Each wire, which measures a mere eight nanometers in diameter, can hook a different prey. Heath is designing the system so that only one nanowire is “live” at a time, endowing the nanolab with such exquisite sensitivity that, currently, a sample need contain only 50 to 500 molecules of a specific protein for the nanowires to detect its presence. In the future, the hooks will also be able to snare specific sequences of DNA. Meanwhile, Caltech physicist Michael Roukes and his group are making nanocantilevers that can detect protein-protein interactions, the critical interplays that determine many of the biological events in the body. Roukes attaches protein receptors to the tips of the nanocantilevers. When a specific protein binds to a receptor, it causes a tiny movement, which induces an electrical impulse that indicates both that a protein-protein dalliance has occurred and the strength of the interaction.

The alliance hopes to move the nanolab into clinical applications by working with two researchers at UCLA: Michael Phelps, who invented the positron emission tomography scan, and oncologist Charles Sawyer, a leading expert in prostate cancer. But Aderem stresses that the nanolab project remains in its infancy. “If we get this functioning in 10 years, I’d be delighted,” he says.

It takes a leap of faith to think that a decade from now, a nanolab will be able to decipher from a single drop of blood what Aderem calls “the molecular fingerprint of a cell,” and that this information will tie into a systems biology database that will give drugmakers and clinicians a dramatically improved ability to help people live healthier, longer lives. But great accomplishments begin with great visions, and this one has spectacular technologies behind it, the likes of which biomedicine has never seen. “When I first got into this, I felt the same way I did when we originally cloned genes,” Aderem says. “My god. The power.’”

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Tagged: Biomedicine

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