Researchers at the Case Western Reserve University School of Medicine have established the Case Center for Biomarker Structure and Integration for Sensors (BioSIS), a program to advance biosensor technologies using biophysical techniques to understand and improve sensing of markers of stress and fatigue.
With $2 million through the Nano-Bio Materials Consortium, a public-private partnership created by the federal government to fund research and development for innovative medical technology, BioSIS is collaborating with the U.S. Air Force Research Laboratory (AFRL) in Dayton and the U.S. Air Force’s 711th Human Performance Wing to develop technologies that detect biological indications of stress and fatigue in real time to monitor and improve pilot performance.
“Our collaboration is focused on understanding what is happening at the core of the sensor, where the sensing elements recognize and capture stress-related molecules,” said Mark Chance, vice dean for research at the School of Medicine, who is leading the BioSIS project. “The discovery and optimization engine that is the BioSIS program will drive the invention of new sensing approaches with wide-ranging implications for biology and medicine.”
In many cases, stress can be helpful: Hormones produce a strong urge to respond to sudden danger, heightening a sense of awareness and triggering the fight-or-flight response. However, high levels of acute stress can produce a paralyzing effect—with disastrous consequences for pilots.
More than a psychological state, stress has a clear biological component where the body suddenly releases special hormones that produce a feeling of extreme distress and anxiety. Among those is a chemical called neuropeptide Y (NPY) that transmits signals throughout the nervous system and is an important biomarker for stress.
The BioSIS collaboration with AFRL is focused on new types of biosensors capable of sensing stress and fatigue biomarkers present in sweat and other body fluids. The sensing is done using a capture strategy by designing protein molecules that specifically bind and capture the “target” molecule—in this case NPY. Once that capture occurs, the sensor’s electrical properties change, producing a real-time electrical response that can be directly detected.
The long-term goal of this approach is a wearable biosensor capable of real-time monitoring for dangerous biomarker changes to provide an added safety net for Air Force pilots. These type of sensors could also serve other purposes, such fatigue and fitness tracking for a long-term study; as a single-use sensor as part of a medical diagnostic test performed at a hospital or doctor’s office; or even in point-of-care applications for multiple health readouts.
“To meet the growing need for training a prepared and responsive Air Force, our collaboration is intended to produce improved technology at the human-machine interface—ultimately resulting in wearable monitors that provide real-time observation of biochemical and physiological markers correlated to human performance,” Chance said. “The project includes the initial discovery of novel sensor types and building prototype devices for testing—up to understanding market needs for commercial devices.”
Using the X-ray foot-printing of Biological Materials beamline of the National Synchrotron Light Source II, a U.S. Department of Energy Office of Science facility at Brookhaven National Laboratory in New York, Case Western Reserve and AFRL researchers have investigated the molecular structure and binding behaviors of several sensors in capture studies with their target biomarker hormones.
CWRU researchers are using multiple integrated biochemical and biophysical technologies to identify new biomarker-response elements and to understand and improve current sensing strategies. Foremost in these techniques is the use of protein footprinting, a technology Chance developed that in this case uses radiolysis—the splitting or activation of water by X-rays—to generate reactive chemicals in solution (hydroxyl radicals) that can identify how the sensor captures its targets.
The extent and site of the labeled regions are detected by mass spectrometry, revealing the “patch” where a biomarker binds in experiments with and without the target molecule as well as revealing associated changes in sensors or the targets that accompany binding and recognition.
“The resolution of the X-ray footprinting approach allows us to obtain an atom level understanding of biosensor structure and their interactions with their biomarkers,” said David Lodowski, assistant professor of nutrition and associate project lead.
Other Case Western Reserve researchers on the project include: Janna Kiselar, assistant professor; Erik Farquhar, research scientist and XFP beamline scientist; Michael Sullivan, XFP beamline engineer; Rohit Jain, postdoctoral scholar; Benlian Wang, mass spectrometry specialist; and Maita Diaz, assistant director. The team includes CWRU consultants Elizabeth Berezovsky and Subbakrishna Shankar, who lead the project’s intellectual property and commercialization efforts.