Bio-X builds on RIT's core technical strengths to address biological, health-care, and medical challenges of the 21st century through interdisciplinary research.
by: Kara Teske May 2009
By pairing science with technology, engineers at RIT are helping to expand the fundamental understanding of some of the most basic biological processes, while working to develop the next generation of biomedical technologies.
Researchers in the Kate Gleason College of Engineering are using computational modeling to recreate physiological systems that enable scientists to predict activities within the body. By understanding the fundamental fluid mechanics within the body, researchers will be able to develop targeted treatments and devices that help to address some of the most dire health conditions facing our nation.
Understanding the interactions between fluid forces and cellular adhesion inside branched microvessels—the smallest intersections of blood vessels—could aid in the development of novel treatment strategies for cardiovascular diseases. Through a combination of experimentation and computer simulations, sponsored by the National Institutes of Health, Dr. Kathleen Lamkin-Kennard, assistant professor in the department of mechanical engineering, is working to predict fundamental fluid flow characteristics in branched microvessels.
Evidence suggests that many common disease states may have an inflammatory component that originates at a fundamental level, since it is in the venular microcirculation where white blood cells (leukocytes) interact with the vessel wall during the inflammatory response. However, little research has been conducted to understand the distribution of white blood cells in branched post-capillary venules and to evaluate the factors, such as fluid dynamics that contribute to the adhesive process.
Lamkin-Kennard and her team of undergraduate researchers are using a combination of computational fluid dynamics (CFD), in vitro experiments, and in vivo data analysis to characterize the distribution of adherent white blood cells in branched microvessels and how physical forces affect what white blood cells do.
"Traditionally, scientists look at a flat geometry, but if you look at the vessels within the body they are branched and twisted," says Lamkin-Kennard. "By recreating this environment in the lab, we can have a better understanding of the whole chemical-physical interaction."
John Jung, 4th year biomedical sciences student and Christopher Barrett, 4th year mechanical engineering student, have been working alongside Lamkin-Kennard to set up and perform the experiments. Using in vivo data from the University of Rochester, the team has microfabricated a 3-dimensional model of the branched microvessels. The microscale branches are coated with selectin—the same protein found inside blood vessels. Microspheres are then bioengineered to behave just like white blood cells. The microspheres are rolled through the microfabbed vessels, creating a controlled environment to study the distribution of rolling and adherent cells. The data collected provides vital information about how the simulated cells behave in the branches, such as where the cells adhere, how fast the cells roll at different locations, and how the flow affects the paths the cells follow.
The CFD analysis provides additional information about the fundamental fluid dynamics in the branches that cannot be obtained from the lab. By pairing these approaches together, the researchers can better characterize the behavior of white blood cells in the branched microvessels.
Their research has shown white blood cell counts are highest at the junction points between the converging branches. Importantly, this general observation holds true regardless of the specific geometrical configuration of each converging branch. Understanding how fluid forces contribute to this observation is the next piece of the puzzle.
"By understanding the whole chemical-physical interaction there is great promise for advancing the understanding of the inflammatory response in many disease states and could aid in the development of targeted drug or stem cell delivery methods, or development of microsensors or microrobotic devices," says Lamkin-Kennard. "Since metastatic cancer cells use the same mechanisms as white blood cells to roll along vessels walls, we will also have a better understanding of metastasis," adds Jung.
Nearly 35 million Americans have some form of chronic lung disease, which leads to approximately 400,000 deaths per year. Being able to predict how particles of aerosolized medications or airborne pathogens travel through the lung is crucial to understanding the physiological conditions that affect particle deposition and absorption into the bloodstream. Until now, little work has been done to examine how airflow and mass transport differ in diseased lungs compared to healthy lungs. Dr. Risa Robinson, associate professor of mechanical engineering, has completed the first-ever study that uses anatomically accurate healthy and diseased lungs to characterize and compare the fluid flow.
Using a replica human lung cast, computer models and large-scale physical models of the alveolar sac were created for both geometries—healthy and emphysemic. The 3-dimensional model is 75 times its natural size and mimics realistic breathing patterns, based on a breathing curve identified in a healthy female. Since emphysema patients breath differently than healthy patients, the experiment will help to collect data that can be incorporated into the model to account for the different tidal volumes and frequencies found in emphysema patients.
Using a monochromatic MotionPro X3 camera, the motion of the fluid inside the alveolar sacs is captured. Robinson and her research students are then able to use Particle Image Velocimetry (PIV) to examine the fluid flow in the model and quantify the differences in where the particles deposit in a healthy lung as compared to the emphysemic lung. "By using the model we can for the first time look at localized deposition within an individual cell," says Robinson. "This type of assessment has never been done before."
The experiment, funded by the American Cancer Society, has provided convincing evidence that recirculation does not occur in the alveolar sacs of the healthy or emphysemic lung, a theory historically used to explain the mixing of inhaled air with residual in the lung. Now, Robinson's students are working on new theories to explain the mixing. The work also shows that particle deposition will happen more quickly when lungs are healthy compared to emphysematous lungs. Understanding the variances in particle deposition in healthy patients compared to emphysemic patients can lead to better diagnosis and treatments.
In 2007, 2,210 heart transplants were performed in the United States. However, thousands more adults would benefit from a heart transplant if more hearts were available. The lack of available donors has spurred development of artificial mechanical heart devices as an alternative to heart transplants. In collaboration with the Utah Artificial Heart Institute, Dr. Steven Day, assistant professor of mechanical engineering, is engineering a left ventricular assist device (LVAD) that aims to increase the mechanical life and decrease the damage caused to blood.
The device uses magnetic levitation instead of mechanical bearings found in LVAD models available today. "The problem with most devices is that fluid mechanical stresses destroy red blood cells or contribute to clotting. By using magnetic levitation there is no mechanical wear on the parts and the fluid mechanics can be better controlled," says Day. An understanding and ability to predict and control the flow inside the pump is critical in the development of the device.
The pump consists of two systems—magnetic and fluid—each developed in parallel. Compared to current LVAD devices, the magnetic system has fewer parts and no flexible materials, which increases the durability of the device. Pathways to the pump are clear with relatively large clearances between each moving part, which limits blood damage. "Current devices approved by the FDA have a limited lifespan due to blood clotting or mechanical design. Using magnetic levitation should solve this issue," adds Day.
The team is using magnetic finite element analysis to determine the magnetic fields and resulting magnetic forces for the individual components and interactions of neighboring magnets. Researchers are working to characterize these magnets to develop a more robust magnetic system. "Given the nature of magnets, in theory if the device can last for a month, it can last a very long time," says Day.
Although the pump rotates at a constant speed, flow through the device is pulsed due to the way that it's connected to the native heart. However, this leads to a complicated time-dependent flow within the device and requires that the magnetic system is fast and robust.
After two years of developing the fluid and magnetic systems in parallel, a complete functional prototype of the novel device has been created. Once some refinements are made to the magnetic system, Day plans to test the device in animals. "This technology presents great promise for the next generation of LVADs. By incorporating magnetic levitation into a simple flow path, the issues of mechanical damage and blood damage will be eliminated, increasing the efficiency of LVADs," says Day.
Development and testing of the pump is sponsored by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health.