Development of a Microfluidic System Incorporating with Material Regulation Property for on-Chip Impedimetric Monitoring of Cancer Stem Cell Selection and Anti-Cancer Drug Screening

Substantial evidences from recent studies showed that solid tumors contain a subpopulation of cancer stem cells that may induce resistant to chemotherapy. Conventionally, selection of cancer stem cells from a pool of cancer cells is based on flow cytometry using specific stem cell surface markers. Then, anti-cancer drug screening is performed based on traditional two-dimensional (2D) culture. This is a series of processes and time-consuming and labor-intensive. Also, 2D cell culture cannot well mimic the native cellular microenvironment since animal cells natively inhabit in three-dimensional (3D) environments. Therefore, in order to tackle these limitations, a microfluidic system incorporating with material regulation property is proposed to provide a well-defined 3D environment for the real-time impedimetric monitoring of on-chip selection and chemosensitivity of cancer stem cells. In this project, a microfluidic system is developed and composed of a 3D culture chamber with a pairs of vertical electrodes located at its opposite sidewalls and medium perfusion fluidic channels upon the chamber. Nasopharyngeal cancer (NPC) cells encapsulated in fibrinogen gel are cultured in the chamber. A steady and homogenous 3D culture environment is constructed for faithfully exploring the physiological responses of cells to extracellular conditions. After 5 days culture, formation of colony in the gel occurs based on the stiffness of the fibrinogen gel. Afterward, anti-cancer drug is perfused to the chamber for chemosensitivity test up to 2 days. During the entire culture process, impedimetric monitoring for quantifying the cell characteristics is simultaneously conducted to provide an on-site, real-time, non-contact, non-label, and non-destructive cellular analysis. The proposed system can conduct a series of processes, including stem cell selection and anti-cancer drug screening, on a single microfluidic system. High throughput and real-time monitoring of cancer stem cell characteristics is performed to investigate the drug resistant of NPC cells. The duration of this project is planned for 3 years. In the first year, design and fabrication of the microfluidic system will be conducted. Also, perfusion 3D cell culture will be investigated to demonstrate the feasibility for mimicking native cellular microenvironment. In the second year, on-chip cancer stem cell selection will be studied using the developed system. Also, impedimetric monitoring of the formation of colony will be investigated. In the third year, chemosensitivity of cancer stem cells will be investigated and monitored by impedimetric measurement. The results will be also evaluated by the conventional biological assays.

Project ID:PB10308-4453
External Project ID:MOST103-2221-E182-004-MY3