Abstract 3924: Single-cell mechanical characteristics of human breast cell lines analyzed by multi-constriction microfluidic channels

Abstract

Abstract Studies of the mechanical characteristics of single cancer cells have shown that non-metastatic and metastatic cells have significant differences in stiffness. We used a microfluidic multi-constriction channel device to differentiate cancer cells and normal cells based upon differences in their mechanical properties. We fabricated the multi-constriction channels on a silicon wafer with SU-8 photolithography and polydimethylsiloxane (PDMS) soft-lithography, followed by PDMS and glass bonding after plasma treatment. The multi-constriction microfluidic channel contains five constriction channels each 50 μm in length separated by relaxation sections of 50 μm between every constriction channel. We used MDA-MB-231 as the cancer cell line and MCF-10A as the normal cell line, and utilized a smart phone to record video via a microscope. Our measurement by smart phone slow-motion video through microscope reliably collected the velocities of over 200 cells. We focused on comparing the initial velocity change due to cell deformation at the entrance of the first constriction channel and the exiting velocity at the last segment of the final constriction channel, where the cells have experienced sequential deformations. The multiple deformation paradigm tests cells’ resilience towards deformation and shape recovery. Cancer cells recovered back to a round cell shape quickly, and therefore experienced deformation at the entrance to each constriction channel, with a net result of a decrease in velocity. The initial velocities of MDA-MB-231 cells were ~1.1 mm/s, and exiting velocities were ~2.2 mm/s. In contrast, normal cells deformed slower initially, but reached a higher velocity after two or three deformations, because normal cells stay in a rod-like shape without fully recovering back to an original spherical cell shape. The initial velocities of MCF-10A cells were ~0.5 mm/s, and exiting velocities were ~3.8 mm/s. When normal cells enter the fourth and fifth constriction channels, the cells’ shapes were almost fixed. The entrance time of cancer cells into the fourth and fifth channel was longer than the normal cells. After calculating the velocity increments in the fourth channel and fifth channel compared to the initial velocity, the Matlab scatter plot of the velocity data of each MDA-MB-231 (n= 108 cells) and MCF-10A (n= 105 cells) cells showed clear separation of the two cell lines into distinct regions. Algorithms based upon these criteria successfully differentiated ~94.4% of the cancer cells from normal cells. Our experimental results indicated that multi-constriction microfluidic channels can be used to differentiate metastatic MDA-MB-231 and MCF-10A cells at the single cell level and may have further applications in high-throughput cell sorting and analysis. The authors would like to thank National Institute of Health (NIH) R21CA210126 for supporting this research. Citation Format: Xiang Ren, Parham Ghassemi, Hesam Babahosseini, Jeannine S. Strobl, Masoud Agah. Single-cell mechanical characteristics of human breast cell lines analyzed by multi-constriction microfluidic channels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3924. doi:10.1158/1538-7445.AM2017-3924