Where engineering meets biology, the work ranges from diagnosing voice disorders to tracking toxicity in the brain.
As a mechanical engineer, Yuling Yan analyzed machine vibrations to find clues that a bearing or gear might fail. She was in the midst of this research as a faculty member at the University of Wisconsin, Madison, when she met an ear, nose, and throat doctor from Malaysia who had come to the United States for graduate school. Yan and her friend, Kartini Ahmad, chatted about their work, one talking about mechanical systems, the other explaining how our voices work. Through these conversations, Yan realized that the same concepts she used to study mechanical vibration also applied to our vocal cord vibrations.
Yan then turned her engineering mind toward biological questions. Now an associate professor of engineering at SCU, she works with Ahmad and other collaborators, developing new ways to image the structure and movement of human vocal cords.
Biomedical engineers apply the principles of physics, biology, and engineering to solve biomedical problems, often to improve human health. They build human tissue in a dish, design better materials for use in joint replacements, and develop techniques to capture high-resolution pictures of the organs in our bodies. They also bring an engineer’s sense of function and efficiency to the innate curiosity of scientists uncovering biological causes of a particular disease.
The growing Department of Bioengineering at Santa Clara reflects the increasing role of bioengineering as part of health care overall. What started as 27 undergraduate students specializing in bioengineering as part of a general engineering degree in 2008 has now expanded into an official department with about 150 students, including graduate students in a new master’s program. Yan chairs the department.
Imaging vibrating vocal cords
Yan develops methods to image the vibrations of human vocal cords. She hopes these tools can help doctors diagnose a variety of voice disorders, including tremors that could be an early indication of Parkinson’s disease.
Often, damaged vocal cords look normal in pictures, as the problem lies in their function, not structure.
Without special training, doctors may not be able to recognize vocal tremors by listening to a patient speak. Taking pictures of vocal cord tissue may not help them diagnose a problem, either; often, damaged vocal cords look normal in the pictures, as the problem lies in their function, not structure.
Instead, doctors specializing in vocal disorders visualize the vibrations of the vocal cords using a stroboscope. This instrument has a tiny camera with a flashing light on the end, essentially creating a trippy dance-club effect for vocal cords. The flashing strobe lights make the vocal cords’ vibration appear in slow motion.
But slow motion is not the same as capturing every one of the 100 to 400 vibrations of our vocal cords each second. So Yan is developing an imaging system using a high-speed camera to capture those true vibrations. The camera peers down a patient’s throat like the stroboscope, snapping 2,000 pictures a second. A computer program tracks the movement of the vocal cords in each image and converts that movement into a wave pattern that represents the vibrations.
Buried in that wave pattern are clues to possible voice disorders. These clues include changes in pitch or volume, as well as patterns that tell doctors how the cords open and close. Yan’s software provides data archiving and image processing, and it analyzes the vibration patterns, searching for information that might help a doctor diagnose a problem.
“There are a lot of engineering methods involved to take care of this vast amount of data,” Yan says. “It doesn’t mean anything to a clinician unless you process it, analyze it, and deliver some useful parameters.”
This new imaging method is still in development, so it’s not widely used in clinics yet. Yan collects high-speed images from patients with voice disorders who visit Krzysztof Izdebski, a doctor in San Francisco who collaborates on the project and serves on the advisory board for SCU’s bioengineering department. Now Yan is comparing those images to pictures of normal vibrations from healthy volunteers. The differences between the two sets of vibrations help Yan identify signatures for particular voice disorders.
Prashanth Asuri, an assistant professor who joined the bioengineering department last year, wants to improve human health by understanding what makes us sick, specifically which chemicals harm brain development. He’s pulling together methods from past research experience at universities and a startup company to develop toxicity tests using "realistic" chunks of brain tissue—that is, brain tissue re-created outside of the human body that realistically predicts response. If successful, his tests could replace animal testing to identify chemicals that affect brain development.
A preliminary list of chemicals that affect brain development from the U.S. Environmental Protection Agency includes lead, nicotine in tobacco, and the artificial sweetener aspartame. Lead, for example, can lead to a shortened attention span as well as impaired memory and language skills. Since wide recognition of these effects in the U.S. in the 1970s, lead has been largely eliminated from gasoline and paint.
But only a small percentage of the thousands of chemicals used in industry have been tested for human neurotoxicity. Even fewer are known to affect developing brain tissue. That’s partly because animal testing—the way neurotoxicity has typically been determined—is time consuming and expensive. It also bumps up against ethical objections. As a consequence, representatives of 15 U.S. federal regulatory and research agencies formed a committee known as ICCVAM with a goal to find alternatives to animal testing. And yet there’s a recognized need to increase testing of industrial chemicals’ effect on human health and the environment; five years ago the European Union’s REACH directive went into effect, with more substances being tested each year.
For two years Asuri worked with Solidus Biosciences, creating microarray biochips that encapsulate liver enzymes. Drug makers dose the cells with medicines in development and determine if they damage tissue function.
But those tests, and others in development, use cells programmed to continuously divide—not exactly like the tissue in our bodies. So Asuri plans to develop similar toxicity tests using engineered tissues that resemble those in our bodies: three-dimensional chunks of tissue grown from human neural stem cells.
These stem cells, however, have one special trick. They glow red or green when they reach particular stages of development.
Asuri and his students begin toxicity tests by triggering neuronal development using a few chemical cues. Then they squirt in a potentially toxic chemical.The cells grow enough to glow, and a machine counts the cells based on the brightness of the glow. A decreased cell count means the chemical either killed the cells or halted their development; the test also allows Asuri to identify particular developmental stages affected by the chemicals.
These tests with engineered tissue could help researchers screen several chemicals simultaneously. That means Asuri might be able to test many of the unknown chemicals for toxicity. Neurodegenerative diseases like Parkinson’s and Alzheimer’s disease may have connections to chemical exposure. If so, Asuri's tests could lead to steps to prevent the neuronal damage.
Asuri develops these tests using known methods in tissue engineering and cell function testing. He’s just adapting the methods for a new purpose. “In that sense, I’m an engineer, not a biologist,” Asuri says. “I look at what has been done and use that in a way that’s readily applicable.”
He’s also incorporating these tests into a laboratory course for undergraduate students. Thus the next generation of bioengineers begins to develop solutions to medical problems that may affect us as we age.