Design, fabrication, and testing of a microfluidic system for cardiac cell culture.

摘要

Cardiovascular disease (CVD) is the leading cause of death in the United States and accounts for nearly 1,372,000 deaths each year. In addition, ∼ 81 million Americans suffer from some form of CVD. Understanding the molecular basis of various manifestations of CVD requires cellular-level studies. However, current technologies for cell culture, fail to recreate the in-vivo environment where cells are subject to pressure and stretch as a consequence of normal hemodynamic loading and unloading. Therefore, to study cardiac cells with physiological relevance, the mechanical loading environment needs to be accurately replicated in-vitro. In order to create an appropriate platform for cardiac cell culture, a microfluidic cardiac cell culture model (muCCCM) was designed and fabricated. This system consists of a pump, cell culture chamber, pneumatically actuated collapsible valve and a tunable resistance element in series. By varying the pump flow rate, valve closure frequency and the outflow resistance, various conditions associated with normal and dysfunctional heart function were recreated. A rat left ventricle heart muscle cell line (H9c2) was used to establish proof-of-concept and demonstrate the ability of the muCCCM to sustain cell culture under normal physiological conditions. Microscopic evaluation of these cells using phase contrast and immunofluoresence demonstrated that cells cultured within the muCCCM achieved an in-vivo like phenotype in comparison to static unloaded controls.;Keywords: microfluidics, cardiac, fabrication, cardiovascular disease, heart failure, PDMS thin membrane.