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A Pitt chemist waits for one particular change in a lustrous gel. If it happens, it will signal the emergence of revolutionary technologies from a world that traditional microscopes can’t see.

Small Wonders


Cara J. Hayden


 
  Vladimir Alexeev and Sanford Asher (Tom Altany photo)
 

Slowly, more slowly still, the corners of the lustrous square undulate like the wings of a swimming stingray. The square, about the size of a postage stamp, is floating in a water-filled petri dish. Suspended in its pliant gel are reflective spheres so tiny they can’t be seen, even under the intense gaze of a classical microscope. With each subtle waver, the square shimmers crystalline red, with hints of orange and gold.

Vladimir Alexeev peers through his goggles at the twinkling ruby slip as he gently shakes a white powder—glucose sugar—off a small spatula into the dish. He watches as the water clouds and then clears as the sugar dissolves.

Turn blue, he prays.

For two months, Alexeev, a Pitt postdoctoral chemistry fellow, has been experimenting with the gel square, hoping for a chameleon-like color shift. If the square turns from red to blue, it will mean his early hunches were right and his false starts were worth it. Blue will mean two decades of initial research paid off. Blue will mean a breakthrough in diabetes control. Blue will mean the emergence of a new era of research at the University of Pittsburgh.

Alexeev stares at the square. Then, suddenly . . . blue. He spotlights the petri dish with his flashlight, just to be sure. The glimmering sapphire square winks at him.

“I did it!” he cries, his native Russian accent coloring his excitement.

Before his fellow researchers in the Chevron Hall lab can reply, Alexeev is sprinting past shelves crammed with luminescent vials and speed walking down a hallway lined with renderings of organic molecules. He bursts into his advisor’s office, brandishing the prized petri dish. With a radiant smile, he announces his success to Sanford Asher, Distinguished Professor of Chemistry.

Asher examines the newly blue slip as Alexeev elatedly describes how he attached to the gel square a chemical agent that senses glucose. The two scientists are working to produce a color sensor that can detect sugar levels in tear fluid. Implanted in contact lenses, the sensor would allow people with diabetes to track their sugar levels without repeated needle jabs to their fingers.

. . .

The spectacular color shift is possible because of the properties of the tiny spheres set within the gel. Asher began experimenting with the polystyrene spheres, called colloids, in the 1980s. The colloids are measured in nanometers, a scale in which one nanometer equals one-billionth of a meter. A single red hair in Asher’s beard has a diameter of about 80,000 nanometers. The colloids measure a mere 100 nanometers.

This minuscule measurement scale is the basis of nanoscience (nano means “dwarf” in Greek), a field at the forefront of research efforts at Pitt. Nanoscience involves studying and manipulating particles ranging in size from 1 to 100 nanometers. Asher is one of 40 scientists leading research at the University of Pittsburgh’s Gertrude E. and John M. Petersen Institute of Nanoscience and Engineering, a multidisciplinary center founded in 2002. The institute’s members include researchers from across the sciences—chemists, biologists, physicists, engineers, and physicians.

Research on the nanoscale is nothing new—nanosize molecules, genes, and quantum particles have all been mainstays of study in the respective fields of chemistry, biology, and physics. The difference now—at Pitt and elsewhere—is that scientists are actually manipulating nanosize specks of matter and building structures that have never been created before. These efforts, most notably Asher’s results, are moving beyond the laboratory into practical applications that could significantly change everyday lives for the better.

Through his nanoscience research, Asher devised a method for creating colloids and assembling them in stacked formations. The stacked spheres, containing 10-nanometer flecks of gold or silver (think of a tiny jarful of glittering marbles), can be suspended in liquids or flexible hydrogels like Alexeev’s iridescent square. A glucose-sensing agent is then attached to the square.

When Alexeev added the sugar to the petri dish water, the sensing agent intercepted and interacted with the sugar molecules, causing the colloidal spheres in the gel to crowd closer together. The reduction in space altered how light reflected off the spheres. The result: red became blue.

This sugar-sensing, color-shifting technology has the potential to benefit millions. About 20.8 million people in the United States suffer from diabetes, many of whom need to prick their fingers—in some cases six times daily—to test their blood glucose levels. Patients wearing these specially designed contact lenses could simply look in a mirror at the gel slips embedded at the edge of each lens. If a patient’s sugar level is too low, the slip will appear red. Green will signal an appropriate sugar level; blue will indicate too much sugar in a patient’s system.

The glucose-sensing lens is the first of many sensors Asher plans to develop using his colloid technology. Teams in Asher’s lab are already working on a gel chip that senses bladder cancer, and he hopes to create sensors that detect prostate cancer, stress hormones, calcium, sodium, and lactic acid. A clear sensor implanted in the arm of a patient with a family history of prostate cancer, for example, would turn red at the appearance of malignant cells, before any telltale symptoms developed.

Essentially, the sensors could test for almost any chemical in bodily fluid and give an immediate color-based response, revolutionizing how healthcare providers diagnose diseases. These sensors could ultimately prove faster and cheaper than the bulky analytical instruments housed in today’s hospitals and labs.

The glittering beauty of colloid-embedded materials also has the potential to change the way we color our world. Pitt licensed the colloid technology to PPG Industries, a Pittsburgh-based international corporation that manufactures paints. Scientists at the corporation are using the colloids to create paints that shift from red to green or from blue to black, depending on the perspective of the viewer. PPG is collaborating with automotive manufacturers to examine the possibilities of spraying the paint on cars. Soon, an iridescent car might glisten with a greenish hue while approaching an intersection, only to appear a sporty red while zipping around the corner. Plans are also in the works to spray the shifty paint on cell phones, bicycles, and golf clubs.

. . .

Biochemistry sensors and color-shifting paints are just a few examples of nanoscience’s range of applications. “Basically, this is an area of science that brings together different physical phenomena that can be used to accomplish a variety of different goals,” says Asher. His colleagues at the University’s nanoscience institute are developing metals that are flexible enough to bounce back from a dent, yet stronger than steel; supercomputers that are thousands of times faster than the ones we use today; bone-building nanopolymers that prevent scar tissue build-up in joints; nanotubes that deliver medicines more efficiently in the body; nanopolymer bandages to support healing hearts; and nanocompounds and particles that absorb vast amounts of toxic waste at power plants or quickly decompose toxic nitrates in drinking water.

Pitt’s nanorelated projects are part of a wave of nanoscience research around the globe. Nanoscience has the potential to improve lives in so many ways that the U.S. government increased its nanoscience research funding from $116 million in 1997 to $982 million in 2005. By 2015, nanoscience will be a $1 trillion industry worldwide, according to the National Science Foundation.

“Pitt intends to be a leader in this emerging field that should change the way we think about and live our lives,” says Pitt Provost and Senior Vice Chancellor James V. Maher. “Our nanoscience program is based on our core strengths in the basic sciences, and from there we can pursue potential applications over a broad range through our engineering capabilities.”

To improve and continue Pitt’s nanoscience efforts, the University is unveiling a new Nanoscale Fabrication and Characterization Facility this spring. The $6.1 million research center in Benedum Hall will house powerful equipment that can measure, identify, and modify nanosize particles by directing beams of electrons at nanosurfaces. Pitt is the only institution in the country, and the second in the world, with an eLiNE workstation, which allows researchers to add or remove 2-nanometer particles from materials. Other machines in the facility will help scientists to “see” their structures through maps and atomic-level images created from electrons bouncing off nanosurfaces.

An X-ray diffraction system will allow researchers to measure chemical properties like density or crystallinity and to check for impurities.

“Combining many different tools of analysis, we can understand better what the entire picture is down to the atomic scale,” says Hong Koo Kim, codirector of the nanoscience institute and Pitt professor of electrical and computer engineering. The facility will also provide a shared space for institute members from the School of Arts and Sciences, School of Engineering, and Schools of the Health Sciences, in an effort to foster research across disciplines.

. . .

Multidisciplinary collaboration helped turn Asher’s glucose-sensing contact lenses into a reality. Alexeev’s initial success at turning the colloid hydrogel from red to blue happened in 2000. The excitement didn’t last long, though, because there was a lot of work ahead. Although the square could sense glucose dissolved in water, subsequent experiments found that it could not detect the substance in tear fluid.

Asher contacted David Finegold, professor of pediatrics in Pitt’s medical school and expert in pediatric endocrinology and diabetes, to help adapt the sensor to physiological conditions. Together, their research teams adjusted Aleexev’s square so it functioned at the human body’s normal pH levels. The sensor was also fine-tuned to distinguish between very slight changes in the minute glucose concentrations found in tears. Once the sensor performed under those conditions, the medical-chemistry partnership focused on speeding up the reaction time of the color change so patients would receive the fastest response possible.

In addition to promoting cross-disciplinary research and equipping scientists with the appropriate tools, Pitt is focusing on transferring research findings to the business sector. Besides licensing Asher’s colloid technology to PPG Industries, Pitt has licensed carbon nanotubes—nanomolecules arranged into tiny test-tube-like structures—to Texas-based Zyvex Corporation. The company is producing the nanotubes to coat and strengthen materials like the lightweight bicycle frames used by the Phonak Cycling Team in last year’s Tour de France. Partnering with businesses not only turns researchers’ commercial ideas into reality, but it benefits the companies as well.

“It’s a pretty long road to commercializing new technology,” says Chuck Kahle, director of coating research and development at PPG Industries. “It is very difficult today for an industrial company to have the ability to invest in all facets of a technology and its development.” Kahle cites environmental, health, safety, and capital cost issues as some of the challenges his corporation faces. “I think it’s very important to us to have a university like Pitt lead the way. The ability to work together provides the whole picture.”

Nanoscience findings are also generating spin-off companies. Asher’s contact lenses have spawned Glucose Sensing Technologies, and now Alexeev is serving as the company’s senior scientist. The company is focusing exclusively on developing and manufacturing the contact lenses for diabetics, and Alexeev says they are preparing to conduct human trials soon. Institute codirector Kim’s nano-optics research parented NanoLambda, which is using his technologies to develop faster telecommunications devices.

“I think we are one of the few universities that really have something you can point to as a product that is going to be or has been used in the commercialization of nanotechnology,” says George Klinzing, Pitt’s vice provost for research. In the next decade, he envisions an explosion of Pitt products ready for the market, including a new Asher idea—safe compounds to replace toxic titanium ingredients in sunblock creams. In 2015, people could be applying coats of nanosunscreen before driving to the beach in sometimes red, sometimes green, dent-proof convertibles. The possibilities of nanoscience are virtually endless—even if they’re unseen.

No Small Recognition

 
Schafmeister (left) and Levins with
a clearly non-nanosize model
 
 

Two Pitt researchers were honored in 2005 for their contributions to the field of nanoscience by Foresight Nanotech Institute, a California-based think tank and public interest organization. Christian Schafmeister, assistant professor of organic chemistry, won
the institute’s Feynman Prize in the experimental work category, and his student, Christopher Levins (ENGR ’00), a chemistry PhD candidate, received the institute’s Distinguished Student Award. The professor-student team was recognized for discovering how to synthesize building blocks— nanometer-scale molecules that join through pairs of bonds rather than single bonds. This allows the design of stiff macromolecular shapes, enabling the manufacture of sturdy, predictable nanostructures. Their goal is to create molecules the size of small proteins that should be useful in biomedical and nanotechnology
applications.

More Small Wonders: A Sampling

Anna Balazs
Distinguished Professor of Chemical and Petroleum Engineering
Designing coatings that repair cracks with nanosize particles

Bruce Doll
Assistant Professor of Periodontics
Developing a biodegradable polyurethane substance that triggers cells to repair joints with bone-building proteins instead of scar tissues that often cause further injury

Roger Hendrix
Professor of Biological Sciences
Codirector, Pittsburgh Bacteriophage Institute

Studying nanosize viruses that attack bacteria to develop more effective ways to deliver drugs into the body

Hong Koo Kim
Professor of Electrical and Computer Engineering
Codirector, Institute of Nanoscience and Engineering

Studying how light interacts with metals to determine how electronics and fiber-optic communication lines can be integrated

Jeremy Levy
Professor of Physics and Astronomy
Developing semiconductor islands known as “quantum dots,” which could initiate the next big evolution in computers

Scott Xinjuan Mao
Professor of Mechanical Engineering
Studying nanocrystalline metals to create alloys stronger and more flexible than steel

Hrvoje Petek
Professor of Physics and Astronomy
Codirector, Institute of Nanoscience and Engineering

Using laser pulses to study how electrons move and how they could transmit signals faster than conventional electronics

William Wagner
Associate Professor of Surgery, Chemical and Petroleum Engineering, and Bioengineering
Creating biodegradable polymer patches that are durable and flexible enough to support beating hearts while injured heart tissue heals

Judith Yang
Associate Professor of Materials Science and Engineering
Developing chemical catalysts that rapidly decompose toxins in drinking water





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