IRT3

IRT 3: Ex Vivo and In Vitro Biomimetics for Cellular Response Monitoring
Leaders: Elmer Price (MU) and Yon Rojanasakul (Pharmacy)
Faculty Participants: Bin Wang (MU), Michael Norton (MU), Yuxin Liu (CSEE), Bingyun Li (Orthepedics), Cerasela Zoica-Dinu (Chemical Engineering), Eric Blough (MU), and Parviz Famouri (CSEE)

Background: The goal of IRT 3 is to develop groundwork for a cell-based sensor platform that seeks to replicate the complexity of cell behavior in a chip-based component. These cell-based sensors will advance analytical investigations beyond composition to determine fundamental effects of materials in our environment. To achieve these goals, microfluidic technology that supports in vitro (from cultured cells) and ex vivo (from fresh biopsies) culture will be developed and combined with optical microscopy and downstream integrated nanosensors for analysis of cells that naturally grow in vivo as monolayers. Most mammalian cells rarely function as isolated individual cells and this is especially true for respiratory epithelial cells and vascular endothelial cells, which grow and function as an interactive monolayer of cells. Cell-based microfluidic devices that separate monolayers into individual cells most likely disrupt functions that require cell-cell interactions, rendering them less than ideal as models for behavior of organs and responses to external agents. IRT 3 focuses on both epithelium and endothelium monolayers that simulate artificial tissue, chosen for their barrier, transport, and “first responder” role in the airways and vasculature, respectively. Drugs, toxins, pollutants and other deleterious agents must first pass through these defenses and it is logical to develop tools that exploit these very cells as sensors. IRT 3 Leaders (Price, Rojanasakul) have expertise with both cell culture types.

Approach: IRT 3 will explore development of a cell-based platform that will allow real-time inquiry of physiological responses to external agents. The underlying premise is that monolayers of cells more closely resemble the physiological function of epithelium and endothelium compared to dissociated cells. As a result, it should be possible to determine effects of toxic agents on cell physiology. To exploit cellular responses integrated with microfluidic devices, 1) optimal cell growth and capture methods in microfluidic devices with porous interfaces will be developed; 2) cells will be exposed to physiological fluid flow conditions; and 3) optical and downstream integrated sensor signals will be analyzed to determine cell viability and functionality when exposed to toxins. 
The proposed device is sketched in Figure 1. Fabrication will be facilitated by investment in tools made of materials compatible with individual biological molecules and cells. These tools can use non-silicon materials, including polymers and biomaterials. Use of these materials ensures the interface between device and biological component (i.e., cell populations) will be compatible. Electrodes and optical interrogators will be introduced using a design-fabrication approach that involves contributions and collaborations between life scientists and engineers. Cyberinfrastructure will not only help model flow in cell-covered channels; investment in the communication network and digital tools for promoting collaboration will be of enormous benefit to this geographically distributed effort.