Tech

CARLO MONTEMAGNO is planning an invasion of your body. "We want to make machines we can insert inside cells," he says. Once they're in there, he aims to make them do things that nature simply can't, such as make drugs or generate electricity.

This isn't just loose speculation or an idle dream: it's work-in-progress at Cornell University. Montemagno has already constructed a working biomolecular motor less than one-fifth the size of a red blood cell. The key components are a protein from the bacterium Escherichia coli attached to a nickel spindle and propeller a few nanometres across. Its power comes from ATP, the biological fuel found in every living cell. The motor is just one step on the road to realising an ambitious long-term vision. Next in line is a motor that can self-assemble inside a cell. "We want to get seamless integration between machinery and living systems," Montemagno says.

Advances like these are promising to change the way medicine interacts with living biological matter. Smart implants that deliver drugs precisely when they're needed are already near to hitting the market. Also on the way are electronic devices that tell cells to make specific hormones when your body needs them, and electricity generators that assemble themselves inside a cell and then tap into the cell's own energy source for the power to run. There is no question that machines are beginning to infiltrate the biological workings of life. "Things are incredibly fast-paced at the moment," says Gary Sayler, a microbiologist at the University of Tennessee, Knoxville. "I know some researchers who are talking seriously about micro-robotic surgical techniques," he says. "With the pace of things now you can go from fiction to reality in 10 years."

Machines built on the nanoscale-using parts the size of small molecules-are likely to look very different from everyday devices. "They're not going to be small versions of what we make in the microworld- we're not going to see levers, tweezers and valves," says Mauro Ferrari, Director of biomedical engineering at Ohio State University. "They'll be similar concepts, but entirely different physics because mechanics just doesn't work the same at that scale." Whatever does end up roaming your body, it won't be anything like the miniature submarine in the movie Fantastic Voyage.

The first medical application of implantable nanotechnology is currently proving its worth in trials. Tejal Desai at the University of Illinois has developed a nano-engineered implant that could mean people with diabetes would no longer have to inject insulin. Diabetic rats with the implant have now gone for several weeks without needing insulin injections. "This is the first we've seen of these technologies actually getting past the bench top and being implanted," Desai says.

Her implant is a silicon box around a tenth of a millimetre across containing a sponge of fibrous collagen tissue. The collagen is seeded with pancreatic cells taken from a pig, a dog or even a mouse. The crucial feature of the box is that the silicon is peppered with holes just 20 nanometres wide-a human hair is about 100,000 nanometres thick. "These pores control what can go in and what comes out of the capsule," Desai says.

Because glucose molecules are relatively small, they can get into the capsule and wash over the trapped cells. If the cells detect too much glucose in the bloodstream, they start producing insulin. The insulin molecules are small enough to escape into the bloodstream and bring glucose levels down. But bigger molecules-such as antibodies and complement proteins employed by the immune system to attack foreign cells-are too big to get in. This means the body doesn't detect the foreign cells, so the implant isn't rejected. Simple, but effective.

Even more cunning are the "dendrimers" designed by James Baker, director of the Center for Biologic Nanotechnology at the University of Michigan in Ann Arbor. These are spherical molecules painstakingly built up layer by layer from a central core. Dendrimers act as multipurpose tools to deal with infection and damage within the body. They can stain diseased tissue with an image-enhancing dye, and give the offending cell a fatal dose of some drug. Doctors can then check this has worked by using a dendrimer that becomes fluorescent in the presence of the enzymes released by a fatally wounded cell. Shining an ultraviolet laser light into the affected area and recording the light emitted reveals how successful the treatment has been.

Each of these tasks is performed by a separate dendrimer, but Baker has now connected some of these dendrimers together to produce the first multifunctional system. "The most advanced can deliver a drug inside a cell, document that the drug is in there and report back on the cell's response," he says. Baker can carefully control the structure, size and chemistry of the dendrimers, adding exactly what he wants at each layer. It takes this level of precision to ensure that the dendrimers evade detection by the immune system and slip easily into cells, without causing medical complications (see "Thanks, but no thanks").

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