Development of a Nanofiber/Polymer Composited Microfluidic System and Demonstration on Impedimetric Monitoring of Cell Proliferation, Chemosensitivity, Hypoxia, Migration, and Multi-Cellular Co-Culture in 3d Environment

Recently, cell biologists proposed that by encapsulating cells in hydrogel, in vitro three-dimensional (3D) cell culture can well mimic the behavior of cells in vivo. Greater predictive clinical capacity was achieved in the drug discovery and development. However, due to the lack of consumables and equipment for 3D cell culture, conventional culture vessels, e.g., Petri dish and multi-well microplate, are currently used for culturing hydrogel encapsulated cells. Cells suspended in the hydrogel are difficult to be objectively observed and precisely quantified. Also, investigation of specific cellular responses, e.g., migration and multi-cellular co-culture, are not possible to be conducted by using conventional culture vessels. Therefore, a PLGA nanofiber/polymer composited microfluidic system is proposed for high throughput 3D cell-based assays. Hydrogel encapsulated cells are cultured in a nanofibrous membrane and embedded in a microchannel of the microfluidic system. Chemical and oxygen gradient can be respectively constructed in the microchannel by diffusion. Cellular responses under the specific culture environment are investigated including chemosensitivity, hypoxia, migration, and multi-cellular co-culture. Moreover, during the culture course, real-time cellular response is quantitatively monitored by impedance measurement technique. Automatic and high throughput 3D cell-based assays can be realized. Furthermore, after the culture course, immunoassay is directly conducted on the nanofibrous membrane. The protein expression of cells is investigated and correlated to the cellular response under the specific culture environment. This project is planned for 3 years. The first year is to investigate the technique of cell culture in the nanofibrous membrane and develop the nanofiber/polymer composited microfluidic system. The second year is to develop the techniques of the real-time impedimetric monitoring of cellular responses in 3D environment and direct immunoassay on the nanofibrous membrane. The third year is to demonstrate the monitoring of cell chemosensitivity, response in hypoxia, migration, and multi-cellular co-culture. The project brings to realize an automatic and high throughput 3D cell culture and analytical equipment for scientific and pharmaceutical research laboratories.

Project ID:PB10901-0532
External Project ID:MOST107-2221-E182-053-MY3