الفهرس 
Acknowledgment
Future workOnly 14 pages are availabe for public view
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Abstract
Mechanical stimuli play valuable roles in various biological processes at the cellular and molecular levels such as gene expression, adhesion, migration, and cell fate. Studying the correlation between changes in the mechanical properties of biological cells and various diseases has drawn a lot of attention in the last three decades. Recent studies proved that mechanical properties of living cells can be used as label -free markers of cell’s biophysical states. In work reported here, we developed and implemented a high throughput microfluidic platform for mechanical characterization of biological cells based on the time of flight technique. In this technique, cells are forced to squeeze through a microchannel with a narrow constriction where the time cells take to squeeze through is proportional to cell stiffness. Also, cell deformation, the time it takes to enter the microchannel, and velocity through the constriction all reflect stiffness of cells. We optimized the flow parameters and constriction dimensions to achieve highest throughput (50 cells /second) while still being able to extract accurate data about cell flow inside the microchannel. We found that very low flow rates exhibit pulsatile flow due to the stepper motor of the syringe pump used and lead to differences in the characterization parameters of cells with similar sizes. On the other hand, high flow rates force cells to flow at higher velocities inside the constriction, which in turn require faster recording speeds, in addition to low sensitivity when comparing different cells. As a case study, we used the developed platform for testing the mechanical properties of individual eutopic endometrial stromal cells of endometriosis patients (Endometriosis is the presence of endometrium tissue outside the uterus). We found that cells from endometriosis patients can easily deform and flow inside the narrow microchannel at much faster velocities (V=98.604 mm/s, SD= 46.336 mm/s) compared to cells from healthy women (V=57.518 mm/s, SD= 39.421 mm/s). Furthermore, these cells do not exhibit increase in the entry time when cell size increases, which indicate that these cells are more deformable. Moreover, endometrial cells from endometriosis patients exhibit higher elongation indices on average (1.65 ±0.2) as compared to normal women (1.43 ± 0.196). We believe this lower stiffness, and thus higher deformability, enables endometrial cells to migrate to peritoneal cavity. These results prove that mechanical properties of endometrial cells can be used as a screening test to identify patients with high possibility of having endometriosis before trying more expensive and invasive diagnostics such as laparoscopy, the gold standard for diagnosis of endometriosis.