| Above: Professor Younan Xia holds an array of glass vials containing many millions of his gold nanocages, which are making possible ways to image cancer cells in lymph tissue. In his laboratory, researchers also are working on ways to use the gold nanocages to carry biomolecules as attachments that could target cancer cells. (Photo: Joe Angeles)
Visions of Promise
Professor Younan Xia investigates imaginative applications of nanotechnology, and he applies keen observations to a wide range of disciplines: from fuel cell development to medical imaging and orthopedics.
Nothing is too small to know, and nothing is too big to attempt.”
—Sir William Van Horne (circa 1900)
When Van Horne linked the two extremes of the size spectrum 100-plus years ago, he could not have envisioned how small the objects of scientific study would become nor how large society’s problems would be. Nonetheless, he provided a fitting motto for research being conducted today at Washington University. Within laboratories in Whitaker Hall, Younan Xia engineers the tiniest structures—down to one ten-thousandth the thickness of a human hair—as agents to address some of society’s biggest concerns.
Xia says that, increasingly, “technological advances in many areas will rely on nanotechnology,” as the field of miniaturized particles and devices is known. He foresees essential applications in everything from electronics to medicine. For example, a future laptop computer may require no batteries, relying instead on an onboard fuel cell to generate power. Its only requirement would be “a small supply of methanol,” Xia says.
As a student, Xia’s first interest was engineering; however, he trained in chemistry. Coming to Washington University in 2007, he established wide-ranging collaborations and, in the process, combined the two fields to create tiny, effective agents of change. Now, as the James M. McKelvey Professor in the Department of Biomedical Engineering, he follows what he calls “simple ideas” to guide his work applying nanotechnology to clean energy production, imaging, and healing.
The Fuel Cell
Batteries store electrical energy; fuel cells create it from fuel and oxidant sources that react on separate electrodes and must be replenished.
Various combinations of fuels and oxidants are possible, but the hydrogen (fuel) and oxygen (oxidant) version is perhaps best-known. The only by-product of a hydrogen/oxygen fuel cell is a small amount of water, so the process is close to being environmentally neutral.
However, the electrochemical reactions require an electrolyte that stays in the fuel cell and a catalyst to boost the current. The most effective catalyst is platinum, with its attendant cost restraints.
If the catalyst’s efficiency can be improved and its costs contained, the abundance of fuel promises nearly limitless and inexpensive electrical power.
Clean energy production
First demonstrated in 1839, the fuel cell has since held promise—and not much more—as a means for generating electricity from abundantly available fuels with little or no environmental impact. Used initially in the Project Gemini space program, its broad application has been constrained by cost.
Xia explains that the chemical reaction in a fuel cell that produces electricity by freeing electrons from their native atoms requires a catalyst. And the best catalyst is platinum. “But there are perhaps only 3.5 billion ounces of platinum that could be economically mined,” he says. (Much of it is used in catalytic converters to treat gases emitted from internal combustion engines. That rarity makes platinum expensive.) “Most of the cost of a fuel cell is in the platinum,” Xia says. “To make a commercially viable cell, we need to reduce the cost by 75 percent.”
Xia and his group went beyond nanotechnology to the atomic level to re-engineer the platinum catalyst. Beginning with a platinum salt, they used ascorbic acid, or vitamin C, to reduce the precursor to platinum atoms. Then they changed the arrangement of the atoms on the surface of the catalyst to find a new, more productive pattern. The principle follows: Reduce the particles’ size to expose more platinum surface area, thereby improving reactivity.
“But,” Xia says, “small particles tend to aggregate; they move during operation and lose their activity. Our catalyst also had to be stable.” So the researchers introduced a “seed” of palladium onto which the platinum atoms grow, forming arms that are fixed in space. In a nod to the pseudo-biological process by which this growth occurs, the arms are referred to as “dendritic.”
The resulting bimetallic catalyst consists of nanoparticles comprising a nine-nanometer palladium core supporting seven-nanometer platinum arms. The catalyst proves to be robust and roughly three times more effective than those currently available. Xia also points out that the manufacturing process is environmentally benign. “This is a very important feature,” he says.
Thomas E. Mallouk, professor of materials chemistry and physics at Penn State University, says, “Xia’s ability to engineer these complex structures at the nanometer level and to imagine applications in which they might be useful distinguish him as a leader in nanotechnology.”
An efficient, affordable bimetallic fuel cell could one day power everything from computers to vehicles to spacecraft. Of the work, Thomas E. Mallouk, the DuPont Professor of Materials Chemistry and Physics at Penn State University, says: “Xia’s ability to engineer these complex structures at the nanometer level and to imagine applications in which they might be useful distinguish him as a leader in nanotechnology. It is nice to see how his research is breathing new life into some old ideas, such as bimetallic catalysts for fuel cells.”
Seeking even more efficiency, Xia and his collaborators now are aiming for a trimetallic catalyst. By adding gold, they hope to produce a more robust and long-lasting catalyst, taking advantage of gold’s ability to oxidize the carbon monoxide, which is a by-product of alcohol fuels and a poison to platinum.
|Using photoacoustic tomography (PAT), Professors Younan Xia (left) and Lihong Wang for the first time used gold nanocages to map sentinel lymph nodes (SLN) in a rat noninvasively. Wang’s lab is the largest PAT lab in the world, credited with the invention of super-depth photoacoustic microscopy, and Xia’s lab invented the gold nanocages. (Photo: David Kilper)
Xia’s group also engineers nanomaterials that aid in medical imaging by adapting a principle everyone has observed: Normally invisible dust motes become clearly observable when they scatter low-angle sunlight. The investigators are able to see otherwise invisible targets by using gold, because gold is “millions of times better at scattering and absorbing light than biological materials,” Xia says.
Starting with the chemical process of galvanic replacement, Xia’s group deposits gold on the surface of silver nanocubes to create tiny packages that can be tuned—primarily by adjusting their size—either to reflect or absorb light. The silver core of the cube is oxidized and eliminated, leaving a hollow structure known as a gold nanocage. The cages can be used to house antibodies that seek precise targets within the body, such as cancerous cells. Tuned to reflect or absorb radiation, the cages then act as contrast-enhancing agents that highlight a tumor.
Tuned to absorb light, the gold nanocages become effective contrast agents for noninvasive imaging. In collaboration with Lihong Wang, the Gene K. Beare Distinguished Professor in Biomedical Engineering, Xia employs the nanocages to map cancerous cells using photoacoustic tomography (PAT). Again guided by onboard targeting moieties to collect at a site of interest—the lymph nodes, for example—the nanocages efficiently generate a sound wave that results as they absorb light, warm, and expand. Used in this way, the nanocages can minimize invasive surgical biopsy procedures to determine if cancer has metastasized, reducing a patient’s exposure to radioactivity.
The researchers also chemically engineer pores on the cages’ surfaces, transforming them into devices for delivering therapy. Directed to a specific destination—the site of an infection, for example—the pre-loaded drugs can be released upon arrival. Gold’s status as a noble metal means it is non-toxic; by adding polyethylene glycol to the surface, the researchers can shield their nanocages from the body’s immune system, giving them time to arrive and deliver the therapeutic payloads.
• A nanometer (nm) equals one-billionth of a meter.
• The term “nanotechnology” is widely agreed to apply to objects in sizes from one to 100 nm.
• A water molecule is less than one nm in size; visible light’s wavelength ranges from 400 to 700 nm, and germs are roughly 10 to 1,000 nm in diameter.
Orthopedic applications and beyond
When tendons tear from bone, as in a rotator cuff injury,
the challenge of repairing the damage and restoring strength has been likened to sticking a rope (the compliant, soft tendon) to a cement block (the stiff, hard bone). Minus the unique transitional tissue that bridged the junction, and with stress concentrated there, the point at which tendon rejoins bone often fails. But Xia and his colleagues are devising nanotechnology to recreate nature’s gradual, elegant change of composition from tendon to bone.
Again, Xia says, the underlying principle is simple: “If you eject a liquid from a syringe, you get a droplet. But if you apply a voltage to the tip of the syringe, the like charges in the liquid repel one another, and the droplet is squeezed into a very thin line.” If a polymer in solvent fills the syringe, when the solvent evaporates the result is called an “electrospun nanofiber.”
In collaboration with Stavros Thomopoulos, assistant professor of orthopedic surgery at the School of Medicine, Xia collects such fibers and coats them with a gradient of calcium phosphate, the chemical basis of bone. The result is a scaffold that mimics tendon at one end and bone at the other, with a smooth transition between. It can be patched into a torn connection as a guide to healing. Because it is biodegradable, it disappears after cells migrate to the site and begin producing collagen.
The resulting improvement in tendon-to-bone healing may mean better outcomes for patients and the resolution of one of orthopedic medicine’s persistent challenges.
Led by Xia, a core group of 10 postdoctoral students and 16 graduate students pursues these investigations and continues to expand the vision for nanotechnology. Aside from winning and maintaining the work’s necessary funding—from the National Institutes of Health, the National Science Foundation, and others—Xia says that managing those researchers is the most challenging part of his job. Talking to the five subgroups into which they are organized requires at least 10 hours per week.
While he insists that the underlying ideas fueling his work are uncomplicated, the problems he addresses are complex, and the promises are far-reaching. According to Geoffrey A. Ozin, Government of Canada Research Chair in Materials Chemistry and Distinguished University Professor at the University of Toronto, the advances are of central importance. He says Xia is “without question one of today’s most innovative and brilliant, imaginative and productive materials researchers,” making contributions that “are now proving to have immense technological relevance in areas of electronics, magnetics, catalysis, fuel cells, and biomedicine.”