Microfluidic Modeling of Oxygen Delivery
Oxygen plays a critical role in physiological processes, from the cellular to the tissue level. Using microchannels as thin as a few strands of human hair, one researcher at the University of Pittsburgh is developing new approaches to precisely control how our cells can sense oxygen.
Ioannis Zervantonakis, assistant professor of bioengineering at the Swanson School of Engineering, received a $552,782 Faculty Early Career Development (CAREER) award from the National Science Foundation (NSF) for his research on using microfluidic technologies to control oxygen transport in 3D cellular environments. The long-term goal of Zervantonakis’s project, “Illuminating the Effects of Hypoxia on Macrophage Interactions with Airway Epithelial Cells in Engineered 3D Environments,” is to create and use engineering approaches to understand the mechanisms influencing cellular adaptation under dysregulated oxygen levels and to actively modulate these mechanisms to restore tissue homeostasis.
“The first aim of this project is to engineer a microfluidic device where we can control precisely how oxygen is delivered, and then validate the use of this device by studying oxygen-regulated pathways in macrophages and epithelial cells,” Zervantonakis said.
Epithelial cells line our organ surfaces and secrete signals during low oxygen levels (hypoxia) to recruit macrophages, which are white blood cells that kill microorganisms, remove dead cells, and stimulate the action of other immune cells. Zervantonakis’s second aim is to understand how epithelial cells drive macrophage recruitment when they are exposed to a hypoxic environment. His team will use microfluidic modeling to control oxygen delivery, which will culture cells within channels the width of a few strands of human hair contained in a micro-sized chip. Bioengineering PhD candidates Matthew Poskus and Rosy Li and postdoctoral scholar Youngbin Cho generated the preliminary data for this proposal.
“We’re manipulating fluids at the micrometer scale by using semiconductor device fabrication techniques,” Zervantonakis said. “We use similar technology that is used in cell phone microprocessor design to make microfluidic chips that we use to culture cells and control the oxygen environment.”
Findings from this project could lead to the development of therapeutic strategies that combine the delivery of high oxygen levels (hyperoxia) with anti-inflammatory agents in chronic inflammatory diseases like obstructive pulmonary disease or sleep apnea. The team’s microfluidic models could also help design tissue-engineered platforms for neuroimmune or vascular systems with multi-parametric control of oxygen and biochemical conditions.
“Beyond studying oxygen transport in lung epithelial cells and macrophages, the microfluidic chips that we develop can be extended to include additional environmental signals, such as shear stress that is critical for vascular systems,” Zervantonakis said.
Scientifically, Zervantonakis hopes to understand epithelial to macrophage communication mechanisms under hypoxia using microfluidics, but his educational goal is to train new generations of engineers who can seamlessly use quantitative tools to analyze and dissect biological systems.
Zervantonakis plans to introduce concepts of diffusion, microfluidics and immune cell migration through a summer camp offered to underrepresented minority (URM) students at the Pittsburgh Science and Technology High School, develop outreach activities through the Young Women in Bio and the LEADing programs, and offer a mentored research program for high school students through the Hillman Cancer Academy.
“In addition to the fundamental research on oxygen mechanisms, this proposal integrates educational activities from the pre-college to college levels," Zervantonakis said. “With the help of Matt Poskus, Griffin Hurt and Jacob Antonello, we will expand our hands-on activities for high school students through the programs that my colleague Steve Abramowitch leads in the Swanson School of Engineering.”
The Faculty Early Career Development (CAREER) Program offers the National Science Foundation's most prestigious awards in support of early-career faculty who have the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization. Activities pursued by early-career faculty build a firm foundation for a lifetime of leadership in integrating education and research.
“I feel that this is a great recognition by my peers not only for microfluidics research but also for teaching and outreach activities,” Zervantonakis said. “I am honored and thankful to be the recipient of such a prestigious award.”