Caltech’s Dr. Michael Roukes calls for practical applications in nanotechnology.

First, what’s a nano? And what has it done for us lately? Nano—from the Greek word for “dwarf”—means one-billionth. One nanometer equals one-billionth of a meter. Here it is in perspective. A human hair is 100 microns wide. The largest individual cell is around 10 microns—this is the limit of human vision. The cell nucleus measures 1 micron, the equivalent of 1,000 nanometers. Drop down to 10 nanometers to find individual strands of DNA. And at 1 nanometer are individual atoms and molecules.

Nanotechnology research began with applications outside medicine and is based on discoveries in physics and chemistry. One offshoot is nanomedicine—medical intervention at the molecular scale, where much of the research is still preliminary.

To achieve the full potential of new nanotools for clinical medicine, Roukes said, we need to “focus on emerging active nanomachines.” These are complete systems for biological processing and analysis, but scaled down to the size of microchips that are “powered up” to achieve their function.

What are nanomachines? “First, they are produced by Mother Nature,” Roukes explained, as in molecular motors (agents of movement) and ion channels (proteins that control the cell’s voltage gradient). Down in the nano, Mother Nature runs the show; our very bones are self-assembling nanostructures.

Now scientists like Roukes are beginning to duplicate such structures—but how best to design and deploy them? The question has long captured the imagination: folklore is full of tiny heroes like Tom Thumb; in the sci-fi film The Fantastic Voyage, scientists are shrunk and dispatched into a man’s bloodstream to search for and destroy a nasty clot.

“We’ve got to cross a chasm to metamorphose ‘feats’ at the nanoscale into usable technology.”

Nano is the design scale of nature itself. It’s the scale at which we’re made. “Nanotechnology is the unit response at the root of biological processes,” Roukes explained.

Down at that molecular or atomic level, things can change radically, in part because certain properties are size-dependent. For example, on the nanoscale things are markedly influenced by Brownian motion (the random movement of particles suspended in fluid), which means that nanodevices could be slammed like dancers in a mosh pit. And in nanoscale, water doesn’t flow like the water we drink; instead, it affects nano-objects moving in it more like molasses.

Roukes began with a brief history of nanoresearch: “[Nobel laureate] Richard Feynman dreamed of making nanosystems and machines” as early as 1959, but “there was no interest in the early years.”

In the U.S., the field was jumpstarted by the 1992 National Nanotechnology Initiative, which now boasts two dozen federal agencies as partners, NIH among them. Nanomedicine is part of the NIH Roadmap for Medical Research.

For the initiated, Roukes also offered an overview of “techno-goodies” and nanoprojects in development (some of which are funded by NIH). His first topic was advances in the study of proteins, which constitute the machinery within the cell. “No other proteomics technology is as important as mass spectometry,” he said. “A holy grail is measuring and quantifying all proteins operative within a cell.”

Among other opportunities are mapping the forces generated by living cells as they are developed, ultimately with single-molecule resolution; resolving the metabolism of individual cells; and tracking stochastic [i.e., unpredictable] biochemical processes at the level of single molecules—all in real time.

“Nanotechnology is the unit response at the root of biological processes,” Roukes explained.

Roukes’s slides included nanodevices in cell motility experiments. One used a plastic chip with a flow channel, a dandy little thing housed within an intricate, much larger chamber that in turn used fluorescent microscopy to be read out electronically. Think of a microfluidic work station where you watch the cell put out its feet and move as you measure and control it in real time.

Here, “higher resolution reveals new phenomena never seen before—bursts of [cell] activity” and temporal and force resolution; oscillations in force. Roukes described nanomachines to measure metabolic rates in normal cells and cancer cells—and that’s single cells. “This is the value-added of nanoscience,” he said. “Advances in nanoscience have improved calorimeters.”

So what if doctors could find the very first cancer cells in the body and remove them before they formed a tumor?

“We’ve got to cross a chasm,” Roukes said, “to metamorphose ‘feats’ at the nanoscale into usable technology.”

He stressed that such “an unfamiliar fusion of technologies” common to the commercial sector must now reach academe. Commercial applications using nanoscale materials have already yielded myriad products including sunscreens, optical fibers, computer hard drives, eyeglass coatings and wound dressings.

As interactions between molecules and larger structures are mapped and we see the intricate operations inside living cells, Nature’s molecular machines could guide us to build our own. And this effort, said Roukes, is “a monumental challenge that transcends the capabilities of any one lab.”