December 2004
Evidence of Things Not Seen
November 11, 2004
By: Nina Welding
The worthiness of a field of study or the benefit of combining technologies — such as the integration of nanoscience and biotechnology — becomes most apparent when engineers explore how it can be applied across many disciplines to improve the quality of life.
In the first volume of his journal The Writings of Henry David Thoreau, in the letter describing “A Week on the Concord and Merrimack Rivers,” the philosopher, author, and naturalist said, “The newest is but the oldest made visible to our senses.” His reflection is as true now as it was in 1849. People perceive truth from what they see, and from what they cannot see they extrapolate, reason, trust, or fabricate. When they are finally able to visualize an item or idea, it is not necessarily “new.” More than likely it was there all along. Perhaps this is why researchers continually look for ways to see beyond the immediately visible. They explore, observe, and record the “invisible,” so that they can better understand what they are able to see and then begin to use that knowledge.
Such is the case with the nano- and biosensor research being conducted at the University of Notre Dame, as some of the “invisibles” that faculty in the College of Engineering have been exploring involve activities on the nano scale. Nanotechnology describes the process of creating new structures or systems atom by atom. It focuses on materials whose components exhibit novel properties — physical, chemical, and biological — due to their size: from a single nanometer to 100 nanometers. And, its potential is enormous. According to the June 2004 issue of Physics Today, “Scientists predict that applications of nanotechnology will go far beyond their current uses — in sunblock, stain-resistant clothing, and catalysts — to, for example, environmental remediation, power transmission, and disease diagnosis and treatment.” Because researchers and investors continue to envision a world with molecule-sized clot-breaking machines and drug-delivery devices, the annual worldwide investment in nanotechnology has exceeded $3.5 billion.
Another “invisible” that’s gained impetus in the last few years is biotechnology, which uses living organisms and their by-products to develop or improve plants, animals, and products for specific purposes. Early “biotechnology” included plant and animal breeding techniques and the use of yeast in making beer, bread, and wine. Today, biotechnology includes manipulating genes to tailor new types of living cells for emerging environmental and industrial needs.
Researchers suggest that the potential of the interface of these two key technologies, which has proven to be truly multidisciplinary, lies in the fact that nanotechnology operates at the same level — the molecular or subcellular scale — as biological processes. This new field, which some call nanobiotechnology, integrates elements of nanotechnology and biotechnology in order to develop solutions for some of the problems facing society today, including challenges in the medical, information technology, security, and aerospace industries, as well as in environmental protection.
Medicine: Designing Drug-delivery Vehicles and Diagnostic Devices
One of the hottest topics in nanobiotechnology is its potential for medical applications, especially in the areas of drug delivery and diagnostic devices. Agnes E. Ostafin, assistant professor of chemical and biomolecular engineering, believes that living cells themselves may provide the best clues for developing materials suitable for use as biosensors or drug-delivery vehicles. “One of the projects we’ve been working on,” she says, “involves red blood cells.” These cells are attractive for research because they have a specific function: They transport oxygen through capillaries to cells. To do this, they have to be flexible enough to change shape, fitting within different sized capillaries as they travel through the body.
According to Ostafin, the red blood cells of diabetics or people with sickle cell anemia are unusually rigid. They can’t bend or change their shape easily, which can lead to blood clots or strokes. “In our studies,” she says, “we’ve been paying special attention to the proteins within cells. What gives some cells their shape — red blood cells in this case — is a meshwork of proteins.” Ostafin explains that this meshwork responds differently to different biochemical signals. Under certain circumstances, the mesh opens, allowing interaction with the triggering chemical. At other times, the mesh remains closed.
“Once we understand the situations which make this mesh open and close,” says Ostafin, “we can begin to apply that knowledge to create synthetic meshes. Or perhaps we could deliver a drug that would help a cell regulate its sensing of chemicals, so it would begin to function more normally. We could develop synthetic cells (or bags) that could carry a drug to a selected site in the body and then, using the concept of opening and closing the meshwork, design it to interact with the chemical conditions of a specific disease. These are all possibilities, but first we must understand the physical biochemical reactions that are taking place.”
Another project directed by Ostafin involves the self-assembly of nanoshells. These shells, whose hollow cores are approximately 100 nanometers in diameter (the size of one human gene), are so small that they do not behave as expected: Semiconductor materials a few nanometers large begin to emit light, metals become catalytic, and interfacial chemistry dominates kinetics and particle dynamics. “Our goal is to find out how we can learn to control molecular assembly,” says Ostafin, “to make a molecule brighter or to control a chemical reaction, possibly preserving it within a solvent-filled core — so it occurs more efficiently.”
Ostafin and her team have many questions to answer, but the first step, she contends, always involves basic studies. Working with several graduate and undergraduate students, Ostafin has shown that dye molecules placed inside nanoshells glow brightly. “We’ve been working on this project for some time and have developed many different recipes to make a variety of particles,” she says. “We believe they could prove to be useful mobile sensors, perhaps even tracking cancer in the body.”
According to Ostafin, coating the outer surface of the nanoshells with other chemicals helps the structures evade the body’s immune system while targeting specific tissues. “Once the shells have attached to the target,” she says, “they ‘glow,’ making the targeted molecule or cell much easier to see for diagnostic purposes. At that point we can consider tailoring the disassembly of the nanoshells, so that they can either deliver a therapeutic payload to the site or signal physicians when the biochemical environment near the targeted tissue is abnormal. This additional information would improve a physician’s ability to design a treatment regime or track a patient’s progress.”
Ostafin stresses that her team is not developing “a cure for cancer,” although she is excited about the potential medical applications of this research. “The most important thing to remember about the nano- and bioengineering efforts at Notre Dame is that there’s scientific merit in the work that’s occurring throughout the college,” she says. “When we understand a system, and why and how it works, that’s when we’ve really opened the door for discovery and innovation.”
In fact, a basic understanding of biotechnology is the focus of a laboratory course elective for seniors that Ostafin will be introducing this fall within the Department of Chemical and Biomolecular Engineering. Ostafin believes the lab experience will give students hands-on opportunities to use the tools of biotechnology, allowing them to contribute more meaningfully to this growing field.
For more information on Ostafin's research, visit www.nd.edu/~aostafin
Security: Uncovering Invisible Threats
Although hundreds of security efforts have risen in the wake of 9-11, this particular project of Alan C. Seabaugh, professor of electrical engineering and associate director of the Center for Nano Science and Technology, began with a call for proposals in 1999, when the United Engineering Foundation requested papers on the development of anti-terrorist technology. Seabaugh’s idea was one of the four selected from a total of 920 proposals. His concept focused on the creation of a handheld biotoxin analyzer that could be used at potentially contaminated sites, such as the aftermath of a terrorist attack or an industrial accident.
Instead of using a light source to illuminate a toxin, which is a traditional way of “seeing” dangerous substances, Seabaugh’s expertise in nanoelectronics led him to suggest using microwave reflection. The use of microwaves would provide the same accurate measurements as the typical optical method but allow the finished device to be much smaller than other devices, possibly the size of a credit card.
Working with graduate students Wei Zhao, Srivatsan Srinivasan, and Qing Liu, Seabaugh designed a semiconductor chip that featured micromachined silicon waveguides through which fluids would travel. The same channels that conducted the fluid would guide the electromagnetic waves.
Completing the requirements for the original proposal in June 2004, Seabaugh and his team demonstrated a prototype of the concept. “The next step ... whether planning to use this device as an attack detector or as a medical diagnostic device,” says Seabaugh, “is to develop microwave tags for specific toxins or chemicals and create a database on the chip for each of those toxins. This type of device could eventually assist in the safe and targeted deployment of personnel and resources to specific sites with detailed information about the type and level of toxin involved. It could make emergency efforts much more effective.”
For more information on the biotoxin analyzer, visit www.nd.edu/~nano/projects/chembio.html
Aerospace: Tracking the Wind
Aerospace engineers track the wind and measure its velocity as it whips through cities. In today’s environment, city officials and emergency teams also need this type of information ... to predict the path of pollutants and assess their toxicity.
An ultrasonic anemometer is a device that is currently used to provide three-dimensional wind measurements. But the anemometers available today are too large to obtain the small-scale measurements of velocity and temperature that would be required for many fluid dynamics and security applications. For this reason Scott C. Morris, assistant professor of aerospace and mechanical engineering, is developing the first microsonic anemometer.
Morris’ microsonic anemometer, proposed to be less than 1/30 the size of current devices, will record turbulent flows with up to 60 times the resolution of other anemometers. This will provide better information for the modeling of air flows and chemical dispersion throughout a city. “For example,” says Morris, “a chemical detector on a roof top may alert officials to danger, but alone it cannot provide information on where a toxin came from or predict where it’s going. The effective modeling of cityscapes, using the information provided by a series of microsonic anemometers, would offer the predictive capability necessary to ensure the safety of a city’s inhabitants.”
Morris is working with Gary H. Bernstein, professor of electrical engineering and expert in nanolithography, who will fabricate the capacitor micromachined ultrasonic transducer (CMUT) portion of the anemometer with a 30-micron diameter, the width of a human hair. He has also developed a relationship with a dispersion modeling team from the University of Utah that will assist in the testing phase of the project.
Once produced, Morris envisions testing the anemometer with its CMUT probe in places like Oklahoma City, where officials have already instrumented the city with ultrasonic anemometers. According to Morris, “Oklahoma City is an ideal location because it’s flat. We can measure the approach of the wind, its velocity, and its path very easily. And, because of their smaller size, officials could economically place more of the microsonic devices throughout the city to obtain more data.”
For more information on the microsonic anemometer, visit www.nd.edu/~ame/facultystaff/Morris,Scott.html.
Environment: Creating Safe Water Treatment Systems
In addition to working on drug-delivery and diagnostic devices, Ostafin is collaborating with Jeffrey W. Talley, assistant professor of civil engineering and geological sciences; Michael D. Lemmon, professor of electrical engineering; Patricia A. Maurice, professor of civil engineering and geological sciences and director of the Center for Environmental Science and Technology; and Lloyd H. Ketchum, associate professor of civil engineering and geological sciences, on an environmental sewage treatment project.
“In most major cities in the midwest and northeastern parts of the country, and on the west coast,” says Talley, “combined sewer overflow (CSO) is an important challenge.” In these cities storm and sanitary sewers are often connected, so when there’s a storm, raw sewage and storm runoff can mix together. Cities usually divert the excess sewage into an open stream or river, but because it is untreated, this poses a threat to public health. The team has proposed using an embedded wireless sensor network to detect and control the CSO problem.
As part of a recently funded recommendation to the Indiana 21st Century Research & Technology Fund, Talley and team will develop the network of embedded microprocessors using off-the-shelf components, EmNet. The network would supply data in real-time to a main base which would monitor the sewer infrastructure in municipalities and provide data that could be used to design additional remediation strategies.
Ostafin’s role in the project is to help the team design sensors that would attach to the microprocessors. “It’s a challenge,” says Ostafin, “because it offers a different scale of detection. In many of the other projects we’re working on, we are concerned with detecting one chemical or type of bacteria. In this case, there will be many types of bacteria ... good and bad ... floating through the system. Our challenge is to be able to detect specific types of bacteria without swamping the sensor.” Other challenges include the fact that the sensors must be strong, yet almost disposable, and able to withstand six to 12 months in a sewer. They must also be lightweight and very sensitive.
For more information on the environmental remediation efforts involving biosensors, visit www.nd.edu/~cest.
There are many examples of biologically inspired efforts within the College of Engineering that are being addressed on the nanoscale. In fact, since nanotechnology operates on the molecular scale, and molecules are the building blocks of both biological and inert matter, it shouldn’t be surprising that one of the most exciting new fields of study today combines nanoscience and biotechnology.
Thoreau was right when he said, “The newest is but the oldest made visible ...” These “building blocks” are not new at all. What is new, and what will continue to evolve, is the way in which researchers are viewing these formerly invisible particles of matter ... to see beyond what has been and then apply their newfound knowledge to make a difference in the way people live.
Contact Nina Welding at Nina.R.Welding.2@nd.edu