A new professor of electrical and computer engineering and mechanical engineering who is moving beyond imaging and diagnostics to use ultrasound as a cancer therapy.
A chemical engineer who immersed himself in the world of biologists to unlock the secrets of cellular life.
A theoretician in both aerospace and materials engineering who wants to use electro-active materials to build artificial muscles.
Tim Bigelow, Ian Schneider, and Wei Hong are three young engineers recently arrived at Iowa State to fulfill the college’s mandate to its faculty: to recruit and develop “clusters” of researchers whose interests bestride the traditional scientific and engineering disciplines to develop innovative applications in medicine, agriculture, energy, and more.
Tim Bigelow: Moving Ultrasound beyond Images
A grainy, black-and-white ultrasound image can show an expectant mother the first glimpse of her baby. And while the picture is not entirely comprehensible, it provides physicians with a great deal of information about the health of the child.
Now imagine a more sophisticated form of this technology used on the same woman, one that instead can determine if a mass in her breast is cancerous. Advances in ultrasound such as this are at the heart of Tim Bigelow’s research.
Bigelow, an assistant professor in both the electrical and computer engineering and mechanical engineering departments, came to Iowa State in August 2008 from the University of North Dakota, where his investigation into ultrasound had accelerated to the point where, by January 2007, he received a prestigious National Science Foundation CAREER Award to develop a system to use ultrasound to treat cancer.
He joins a 75-year exploration of ultrasound energy in the medical field, engaging both past uses of the technology, which included treatment for ailments such as brain disorders, as well as the medical imaging that is seen today during prenatal care. Using an integrated approach, Bigelow’s work seeks to make some medical practices more efficient while providing immense benefits to patients.
A measurable improvement
The diagnostic use of ultrasound comes with some imperfections, primarily because it requires a skilled technician to read the image and make judgments based on qualitative attributes. However, incorporating mathematical analysis into the process, as Bigelow strives to do, provides new details to health care providers.
Working with a faculty member in nursing at the University of Illinois, Chicago, Bigelow analyzes the echoes from an expectant mother’s cervix to assess the risk of premature delivery. The team identifies risk indicators, such as an increase in water concentration in the cervix’s lining, by placing a color map derived from mathematical analysis over a gray-scale ultrasound image of the cervix. With this information, they are able to determine if the mother needs to take any action to protect herself and her child.
Faculty members at the University of Illinois, Urbana-Champaign, are spearheading another project in which Bigelow is involved, work that could eliminate the need for a biopsy to diagnose breast cancer and instead offer patients a less painful and less expensive mechanism for assessing their health.
“Reading the echoes from an ultrasound, a physician can determine if a tumor is cancerous without removing any cells or tissue,” Bigelow explains.
A precise treatment
At significantly greater amplitudes, ultrasound can be used for therapeutic purposes as well, offering physicians more control than is typical with most current procedures. Within this research avenue, Bigelow is identifying ways to remove infection from an implant and treat metastatic cancer of the liver.
Common cancer treatments such as thermal ablation can destroy healthy tissue by heating up an entire area to attack a tumor, and surgery often removes good tissue along with cancerous tissue. By contrast, ultrasound can provide a less invasive process that allows patients to recover more quickly and with fewer side effects.
Ultrasound essentially liquefies cancerous tissue as the amplitudes interact with small bodies of gas in the tumor. This reaction causes the gas bodies to expand and collapse violently, Bigelow says, during which cells exposed to the ultrasound are completely fragmented, a process he likens to sending them through a microscopic blender.
With ultrasound offering vast improvements in patient care, Bigelow and his multidisciplinary collaborators are keen to continue their biomedical research.
“While we still have many challenges,” he says, “the potential of our work keeps our ambitions high.”
Ian Schneider: Probing the Secrets of Cells
Ask Ian Schneider what chemical engineers bring to the study of biological systems, and he’ll dutifully cite the core principles of thermodynamics, transport phenomena, and reaction and diffusion systems.
Yet despite an early interest in biology as an Iowa State undergraduate, it wasn’t until graduate school at North Carolina State that the Carlisle, Iowa, native began to see deeper into his own chosen profession and his avocation—all the way to the level of the individual cell.
“As an undergraduate, biology was just another thing in my life, like playing the trumpet,” Schneider acknowledges. “I wasn’t really able to make the connection.”
That would change in graduate school, where Schneider’s fascination with both the biochemistry and mechanics of living cells compelled him to view the two disciplines not as alternative but complementary ways of describing intracellular phenomena. Indeed, the application of engineering principles to biology deepened Schneider’s appreciation of what is in fact an intimate relationship between the mechanical and biochemical aspects of cellular activity within organisms.
A temporary change of community
Yet as he became fluent in the language and practice of biology, Schneider felt something was missing in his professional preparation: a close working relationship with biologists themselves. So instead of a faculty job after the PhD, Schneider continued his apprenticeship in the biological sciences with a postdoctoral appointment at The Scripps Research Institute in San Diego.
His “community” changed virtually overnight, as Schneider was immersed in a world of biologists for whom the professional interests of chemical engineers were secondary at best. And though it’s been a long road to refocus upon chemical engineering, Schneider has no regrets.
“I chose Scripps because Clare Waterman is one of the leading scientists in using fluorescent microscopy techniques to analyze the cytoskeletal dynamics in cell migration,” says Schneider. “She pushed forward an entirely new technique to measure this phenomenon, and I wanted to learn that and bolster my knowledge in microscopy.”
That interdisciplinary risk-taking made Schneider attractive to his alma mater, as the College of Engineering championed “cluster” hiring across disciplines to address 21st-century challenges. And for Schneider, that challenge means nothing less than understanding the intracellular processes that allow both wounds to heal and cancers to spread throughout the body.
“Eventually,” he says, “we need to understand the system as a whole. But in order to understand the system, you have to understand three primary processes: cell migration, cell-to-cell adhesion, and the ways cells communicate with each other.”
‘Listening in’ on a critical communication
As he prepares his research regimen at Iowa State, Schneider says that he and his students will focus on how the mechanical forces exerted by cells affect biochemistry, and how that in turn affects the migration of cells—including cancer cells in metastasis—from one part of the body to another. For instance, he notes, when a cell extends its edge and adheres to its surroundings, it forms mechanically sensitive macromolecular complexes called focal adhesions, which allow the cell to move forward.
However, Schneider stresses, such extension is not spontaneous but instead caused by the transmission of a biochemical signal from another cell. “Cells migrate out of wounds or tumors,” he says. “But they have to migrate for some reason. And the reason is that there are other cells that secrete communication signals.”
Furthermore, he adds, not only do cells “talk” to each other through this biochemical pathway, they also talk through mechanical pathways by rearranging the extracellular environment. By understanding the relationship of biochemical “signals” to biomechanical behavior, Schneider says, chemical engineers can contribute to the development of therapies to speed the healing of wounds and impede the metastasis of cancers within the body.
“Applying an understanding of transport phenomena and reaction kinetics will allow us to better understand that system,” Schneider says. “And then, perhaps, we can come up with ways to influence that communication.”
Wei Hong: A ‘Smart’ Approach to Materials
Wei Hong considers himself a theoretician, yet he seeks to collaborate with experimentalists from across the College of Engineering and the university as a whole as he strives to gain a basic understanding of how various so-called “smart” materials respond to stimuli, and how those responses can be optimized for specific applications.
An assistant professor in aerospace engineering with a courtesy appointment in materials science and engineering, Hong earned BS degrees in computer science and engineering mechanics and an MS in solid mechanics from Beijing’s Tsinghua University before going to Harvard University in 2002 for his PhD in engineering science, followed by a postdoc working in smart materials.
Inspiration from nature
Essentially, smart materials are “smart” because their fundamental properties can be significantly altered by external stimuli such as temperature, moisture, stress, pH value, and electric or magnetic fields. A smart material, for example, might deform as the result of an electrical charge or swell when put into water.
Nature, of course, is full of active materials such as the structures in plants and animals that respond to stimuli in order to adapt to conditions in their environment. Scientists and engineers, therefore, look to nature for inspiration in designing devices and structures that can perform specific functions based upon their responses to various stimuli.
Smart materials have significant potential over the long term for a wide variety of bioengineering applications. For example, a capsule could be designed someday to release its contents when it senses a specific type of diseased cell. Or a polymer that responds to magnetic fields could improve tactile feedback in virtual reality applications to train physicians in a given medical procedure.
The field, though, is still in its infancy.
“We have found that there is a deficiency between our current understanding of the physical behavior of smart materials and what we need to know to take full advantage of their properties,” Hong says. “On the one side, people want to apply these materials to engineering to make things out of them because of their ‘smartness.’ On the other side, our understanding of these materials is very limited, so we are trying to bridge the gap and make both sides better.”
Seeking ‘muscular’ insights
One area Hong has been researching is the development of artificial muscles made from electro-active materials whose shape can be modified with the application of an electric current. The goal, according to Hong, is to optimize shrinkage and enlargement of the material in order to use it as an actuator for an artificial muscle that would expand and contract in response to an electrical impulse, much like a human muscle.
“What has been found is that once the voltage reaches a critical value, the material, which is a thin sheet, gets wrinkles in it rather than expanding or shrinking uniformly,” Hong explains. “We are making a computational model to help us understand this phenomenon. It will tell us how the material should respond both qualitatively—that is, what properties are causing the wrinkles—and quantitatively, which will enable us to predict things like what deformation to expect at various voltages or how much force will result from the deformation.”
Once Hong has developed the model, he will turn to experimentalists to verify the model’s validity. If it is incorrect, then more research into the basic physics underlying the behavior will be required; if correct, the model will be used to determine design parameters to achieve optimum performance for the smart materials.
“What we want to learn from the models is how to optimize the material or structure for the best performance in specific applications,” says Hong, who sees the actuator as a possible alternative to motors for operating robots or micro aerial vehicles. “It will be much more flexible and much smaller than a traditional engine.”