Microsystems for Biological Cell Characterization: Dissertation

This thesis describes three techniques for the characterization of living cells using micro-electro-mechanical systems (MEMS) based devices. The study of cellular function and structure is essential for bioprocess control, disease diagnosis, patient treatment and drug discovery. Microsystem technology enables characterization of very small samples, minimal use of expensive reagents, testing of multiple samples in parallel, and point-of-care testing, all of which increase throughput and reduce the analysis cost. The three characterization techniques presented in this thesis could be integrated into a microfluidic cellular total analysis system to obtain complementary information of cellular function. The first part of the thesis presents the characterization of bovine adrenal cortex capillary endothelial cells by impedance spectroscopy in a microsystem which was realized using microfabrication techniques. The microsystem consists of a small-volume cell culture area defined on PDMS walls on a glass substrate with gold electrodes coated with a self-assembled monolayer to enable cell attachment. As the main result, it was possible to monitor the capillary formation of BACC endothelial cells in a microsystem using impedance spectroscopy. The second part describes calorimetric characterization of Saccharomyces cerevisiae yeast cells using a MEMS-based nanocalorimetric microsensor. The cells are introduced to the sensor membrane in small droplets (~1 µl), and the sensor thermopile voltage output is compared to the output of the reference water droplet to extract the effect of sample evaporation. The third part describes the design, process integration and fabrication of an electrically tunable Fabry-Perot interferometer (FPI) monolithically integrated on a photodiode for visible spectrum measurements. The options for the process integration of separate FPI optical filters are presented. The application of miniature spectrometers based on MEMS FPI technology in biological cell characterization is discussed.