A Fluid Situation
What exactly would a nanosensor to detect such proteins look like? To turn a nanowire into a transistor, the researchers bring each of its ends into contact with metal wires so that a current can be passed through it. They then position an electrode close to the nanowire. Charging this electrode alters the conductivity of the nanowire, turning it “on” and “off” – all familiar stuff to any electrical engineer.
Heath then transforms his nanowire transistors into tiny biosensors. Say, for instance, that one nanowire is to act as a sensor for a particular protein. The researchers coat the surface of the wire with antibodies that will stick to the target protein but not to other molecules. When proteins bind to the antibodies, they interact with the electrons traveling in the nanowire’s surface layer, altering its conductivity. If the wire is only a few nanometers thick, there is a significant – and measurable – change in its overall conductivity. “If the wire is really, really small,” says Heath, “instead of putting a voltage on it, we can put molecules on it, and a chemical event is what causes the transistor to switch.”
Their small size also makes the devices very sensitive. Ultimately, the number of molecules required to produce a reading will depend on how tightly they bind to the receptor groups on the sensor surface; but it might be possible to detect individual molecules. Heath says that, although his group has not yet reached that level of sensitivity, it has succeeded in detecting just a few molecules. (Charles Lieber of Harvard University, meanwhile, has demonstrated nanosensors that can detect a single viral particle*).
But it’s not just high sensitivity that Heath is relying on for easy and early detection of disease. “We can make thousands of these sensors in a very small area,” he says. This means the ability to screen the varied molecular contents of individual cells. Heath is collaborating with Stanford University microfluidics expert Stephen Quake to fabricate chips in which fluids pumped down microscopic channels shuttle single cells into position over a nanosensor array, where they can be studied one at a time.
In the end, all this technology has to be integrated in a device that can be used in the clinic, which means solving yet more technical and practical problems. In 2003, the Institute for Systems Biology, Caltech, and the University of California, Los Angeles, established the NanoSystems Biology Alliance to ensure that the new tools reflect the latest advances in cancer biology and immunology. The diagnosis of cancer and other diseases, says Quake, will be “carried out automatically, in a few seconds or minutes, on just a handful of cells or their contents.” And that conjecture, he predicts, “will be turned into a reality within this decade.”
Philip Ball’s latest book is called Critical Mass: How One Thing Leads to Another.