Abstract One of the common laboratory methods to check the effectiveness of a proposed drug in cancer treatment is the drug in question with cultured cells in laboratory conditions. Cell culture is traditionally performed as two-dimensional monolayers in static environments such as petri dishes or flasks. Due to the fact that the cell is cultured in the flask in two dimensions, it loses some of the inter-cellular connections that are normally three-dimensional in the human body. Because of these differences in cell interaction in two-dimensional cultures (cell-cell and cell- surrounding interaction), as well as differences in access to oxygen, food, etc., as well as differences in the polarity and physical and mechanical characteristics of cells and the impact of them on many on many vital processes of the cell (such as growth, differentiation, response to stimuli, etc.), compared to natural conditions, 2D cultures cannot be suitable models for generalizing the results of pharmacological investigations. To solve this problem, 3D cell culture is suggested. In the present study, a microfluidic system design for the quantitative study of cell migration and invasion with the possibility of investigating and eva‎luating the migration process of invasive breast cancer cells and improving its performance is considered. The overall goal of this study was to make a basic chip suitable for monitoring cell movement. In this microfluidic system, there are concentric semicircles with a distance of one millimeter, and there will be a series of channels perpendicular to the main channels with micron dimensions, which are actually the simulation of capillaries and lymphatic vessels. For this, a basic chip was designed according to previous research. The designed chip was entered into COMSOL software and its performance was simulated. The method of filling the middle channels that contains cells was done using biphasic flow and checking the speed and pressure in the side channel to feed the cells using slow flow. The simulation results showed that in the final chip, the maximum speed and pressure were equal to 3.77 mm/s and 1.26 kPa respectively. Continuingly, according to the simulation results of the basic chip, optimization was done. According to the performed simulation and manufacturing facilities, the height of the channel was reduced from 200 microns to 150 microns. The distances of the concentric semicircles increased from 420 microns to 460 microns. All the angles of the channels in the model chip were 45 degrees, which were respectively changed from the outermost channel from 45 degrees to 35 degrees, the second channel remained unchanged, and the third channel changed from 45 to 55 degrees. The pattern of trapezoids in the chip was also changed. To ensure optimal chip performance, simulation was done on it again. The optimal chip filling is similar to the original chip and its maximum speed is reduced by 0.36%, which is useful for its longevity. The final mold was made using the lithography method. At the end, the desired chip was used in the laboratory for cell testing, the filling of the middle channels and the fluid movement in the side channel were eva‎luated in the channel. MDA-MB-231 cells (20×106 cells/ml) were prepared and mixed with collagen type 1 solution at a concentration of 2 mg/ml. Two microliters of a mixture of cell-hydrogel were loaded into the central channel of microfluidic chip number 1 (related to tumor cells). Afterwards, the microchip was placed in a CO2 incubator at 37 °C for 20 min for gel polymerization to create a three-dimensional structure. Following this, the second channel was filled only with collagen, as stroma, and the microchip was placed in a CO2 incubator at 37 degrees for 20 minutes to polymerize the collagen gel. The next channels were filled with culture medium.

عليرضا فدائي تهراني , امين اله محمدي

مينا ميريان

مهدي كاروان , مهدي كاظمي