Microfluidic system development for detection of single-cell mechanical properties

Abstract

This thesis aims to microfluidic systems have been developed to determine the mechanical properties of cancer cells and healthy cells as a single cell with a holographic imaging technique. The most important innovations brought by microfluidic chips are that they can perform many operations at the same time, cell separation processes, and the microchannels can be continuously identified and followed. They also provide a suitable environment for processing and analyzing cells in a narrow and restricted area. Therefore, the use of microfluidic chip applications in processes such as analysis, evaluation, replication on cells has become widespread. In the microfluidic systems developed within the scope of the thesis PDMS based microchips are produced and designed as a platform in which microchannels are contained, the cells can be immobilized individually and exposed to acoustic effects. HCT-116 (Colon Cancer), ONCO-DG-1 (Ovarian Cancer), MDA-MB-1 (Mammary Cancer) were chosen as the appropriate cancer cell line and HUVECs (Human Umbilical Vein Endothelial Cells) selected as a healthy cell line for the experiments. First of all, a microfluidic system has been developed in which cells can be controlled. In order to control microfluidic systems, the flow must also be controlled. For this reason, a flow rate in the microfluidic system was measured by developing a micro-flow sensor based on diamagnetic levitation. Thanks to this developed sensor, optimum values were determined in the micro-flow system for cell culture studies. Afterward, ultrasonic transducers were integrated into the microfluidic system. Acoustic surface waves were created on cell surfaces using acoustic transducers. These transducers have been used to create discernible waves on the cell surface due to their high-frequency modes. As a result, the acoustic mechanical effect on cancer cells was obtained by the holographic imaging technique. In experiments, acoustic waves were sent in the frequency range between 1 Hz and 2kHz and amplitude range between 3Vpp and 5Vpp applied to determine the mechanical stiffness of cancer cells. Optimum frequency ranges are determined, and results are compared. With these studies conducted in the thesis, a microfluidic system that can reveal the morphological structures of cancer cells based on acoustoholographic has been developed.