Medical Device Daily Washington Editor

BETHESDA, Maryland — The National Institutes of Health has a hand in a large chunk of the latest biomedical research as yesterday's portion of NanoWeek 2009 at the NIH campus made clear, but the take-home message is that diagnostics will soon be profoundly shaped by nanoscale matter. Everyone is familiar with the buckminsterfullerene and the carbon nanotube, but one presenter discussed briefly the use of "buckypaper" as a platform for transplantation of some of the most delicate tissue in the human body, the cells that make up the retina in the human eye.

Discussing the application of nanoscale materials science to diagnostics and other biomedical applications was Meyya Meyyapan, PhD, of the Ames Research Center operated by the National Aeronautics and Space Administration. Meyyapan remarked that with all the fuss over various new configurations of carbon atoms into nanohorns and so on, the carbon nanotube is still "one of the exciting materials" for this area of research.

Carbon nanotubes can be built in electrode arrays to serve as biosensors, and Meyyapan said such constructs can directly interface with deoxyribonucleic acid, ribonucleic acid, various other proteins and a range of microscopic life forms. In this application, nanotubes are often topped with attractor proteins to capture the target molecule or microbial of interest.

Despite the seeming novelty, "carbon-based electrodes have been around for about 100 years," Meyyapan observed, but even now, the difference is all about scale. "The size difference between your target and the electrode is tremendous" in many applications, he noted, hence, scaling down the size of a diagnostic is essential, which also offers the benefit of "dramatically reduce[ing] the background noise" of any required electromagnetic activity in a diagnostic.

One caveat faced by those who would fabricate such devices, however, is that if the electrodes are not sufficiently spaced apart, "they tend to act like one big electrode, and you want to avoid that," Meyyapan said. In an embedded array of carbon nanotubes, most types of interference can be sidestepped by embedding the tubes at an average distance of at least a micron, and Meyyapan told Medical Device Daily that this distance is adequate for almost any amount of wattage one might expect to pump through such an array.

Integrating nano-based detectors with microfluidic technology is something Meyyapan and his team have been "focusing on for the last year or so." One obvious application is the now-famed lab-on-a-chip.

Meyyapan discussed the use of sensors that detect biomarkers in gases and vapors, a more demanding application than detection of biomarkers in serum due to the lower concentrations found in gases. "Some diseases, recent studies show, actually [present] some gases and vapors in our breath in higher concentrations than people who are normal," Meyyapan reminded the audience, so "we need a system consisting of a sensor array" that may require sensitivity on the level of parts per billion rather than the current standard of parts per million. This kind of "absolute discrimination," he said, requires among other things a preconcentrator. For such a unit, however, low power consumption is also desired "because it's almost always battery operated."

For this kind of diagnostic, Meyyapan said the single-walled carbon nanotube offers the surface area needed to detect with high certainty the molecules of interest in this biomarker-poor environment. "It only takes about four grams of carbon nanotubes to get the surface area of an American football field," he pointed out, but such a diagnostic can be turbocharged, too. "Exposing [it] to UV or slightly heating it up can speed up" the process substantially, he said, but he noted that "the most important thing is how you make sure you select the one thing you're looking [to ensure] absolute sensitivity," which he said hinges on the substance used to dope the nanotubes.

In one arrangement assembled to fill this bill, response times were measured "in seconds," Meyyapan said, adding that "the entire thing ... operates on only 50 milliwatts." He noted that a prototype was put onto a Navy satellite payload, and the unit was robust enough to handle the stress of launch.

"The electrode ... is also something you could use for deep-brain stimulation," Meyyapan said, assuming that one is dealing with carbon fiber electrodes at diameters of about 10 nanometers. "We have tested this in vitro," he testified.

As for buckypaper, Meyyapan said this approach to reversing macular degeneration requires a harvest "of healthy cells from your own eye and grow[ing] it in a culture" for reimplantation. However, these cells do not always replant "in the proper architecture" when using other methods of fixation, so the idea is to fix this "by growing them on a culture with a physical support."

Thanks to the flexibility of buckypaper and its ability to cradle the cultured retinal cells, the preliminary results are promising, even if they are not yet deemed definitive. "The results show a confluent monolayer with uniform orientation of cells" on the buckypaper's surface, Meyyapan said, which offers excellent reattachment properties. He said the buckypaper "is easily manipulated during surgery and is well tolerated by the body's immune system.

Meyyapan also noted that the protein-conductor interface bears some resemblance to work going on in Silicone Valley. "If I made a silicon nanowire, it would be the same thing" that engineers at microprocessor companies are building. "Right now, we are talking to National Semiconductor" (Santa Clara, California) about some of the underlying technology, he said.

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