Development of High Throughput Microfluidic 3-Dimensional Cell Culture Chip System and Its Application for the Evaluation of Chemotherapy Drugs

With the tremendous advances in microfluidics during the past decade, microfluidic systems have been progressively used as versatile cell culture tools for various research purposes due to their several advantageous features. Among the various applications, microfluidic cell culture systems have been widely used in cell culture-based assays (e.g. drug testing). However, most of previous works can not provide a stable, well-defined, and more biologically-relevant culture environment for a high–throughput and high-precision cell-based assay. To tackle these issues, this project aims to develop a microfluidic cell culture chip consisting of 48 microbioreactors for micro-scale perfusion 3-dimensional (3-D) cell culture-based assays. Its main characteristics are the capability of multiplex medium delivery, and the function for both efficient and high throughput micro-scale 3-D cells/hydrogel scaffold, or fresh tumor sample loading. In the first year project, the microfluidic cell culture chip will be designed and fabricated based on soft lithography using polydimethylsiloxane (PDMS) as material. The performance of the incorporated vacuum-driven medium pumping, and cells/hydrogel scaffold loading mechanisms will be experimentally evaluated. Furthermore, a chemosensitivity assay of cancer cells to anti-cancer drugs will be demonstrated using the proposed system. In terms of applications, the ultimate goal of this project is to use the proposed system to assay the sensitivities of patient’s cancer cells to anti-cancer drugs at 3-D tumor tissue, or 3-D cell culture (e.g. cells immobilized in a 3-D scaffold) level. Before we can achieve this, some fundamental questions relevant to the effect of cell culture model on the result of chemotherapy drug evaluation need to be answered. These include: (1) the difference between the chemosensitivity evaluation of cancer cells to anti-cancer drug using fresh tumor tissue model, and the model of freshly-isolated cancer cells in a 3-D scaffold, (2) the difference between the chemosensitivity evaluation using freshly-isolated cancer cells in a 3-D scaffold, and expanded cancer cells in a 3-D scaffold, and (3) the difference between the chemosensitivity evaluation using expanded cancer cells in a 3-D scaffold, and the expanded cancer cells on a 2-D surface (conventional model for the evaluation of chemotherapy drug). In the second year project, researches will be carried out to clarify these issues.

Project ID:PB10007-2300
External Project ID:NSC100-2221-E182-025