We report a combined experimental and theoretical technique that enables the characterization of various mechanical properties of biological cells. The cells were infused into a microfluidic device that comprises multiple parallel micro-constrictions to eliminate device clogging and facilitate characterization of cells of different sizes and types on a single device. The extension ratio λ and transit velocity U of the cells were measured using high-speed and high-resolution imaging which were then used in a theoretical model to predict the Young's modulus E = f(λ, U) of the cells. The predicted Young's modulus E values for three different cell lines (182 ± 34.74 Pa for MDA MB 231, 360 ± 75 Pa for MCF 10A and, 763 ± 93 Pa for HeLa) compare well with those reported in the literature from micropipette measurements and atomic force microscopy measurement within 10% and 15%, respectively. Also, the Young's modulus of MDA-MB-231 cells treated with 50 μM 4-hyrdroxyacetophenone (for localization of myosin II) for 30 min was found out to be 260 ± 52 Pa. The entry time t of cells into the micro-constrictions was predicted using the model and validated using experimentally measured data. The entry and transit behaviors of cells in the micro-constriction including cell deformation (extension ratio λ) and velocity U were experimentally measured and used to predict various cell properties such as the Young's modulus, cytoplasmic viscosity and induced hydrodynamic resistance of different types of cells. The proposed combined experimental and theoretical approach leads to a new paradigm for mechanophenotyping of biological cells.
Cells respond to mechanical forces by deforming in accordance with viscoelastic solid behavior. Studies of microscale cell deformation observed by high speed video microscopy have elucidated a new cell behavior in which sufficiently rapid mechanical compression of cells can lead to transient cell volume loss and then recovery. This work has discovered that the resulting volume exchange between the cell interior and the surrounding fluid can be utilized for efficient, convective delivery of large macromolecules (2000 kDa) to the cell interior. However, many fundamental questions remain about this cell behavior, including the range of deformation time scales that result in cell volume loss and the physiological effects experienced by the cell. In this study, a relationship is established between cell viscoelastic properties and the inertial forces imposed on the cell that serves as a predictor of cell volume loss across human cell types. It is determined that cells maintain nuclear envelope integrity and demonstrate low protein loss after the volume exchange process. These results define a highly controlled cell volume exchange mechanism for intracellular delivery of large macromolecules that maintains cell viability and function for invaluable downstream research and clinical applications.
We compute and compare the decay lengths of several correlation functions and effective coupling constants in the many-body localized (MBL) phase. To this end, we consider the distribution of the logarithms of these couplings and correlators: in each case the log-coupling follows a normal distribution with mean and variance that grow linearly with separation. Thus, a localization length is asymptotically sharply defined for each of these quantities. These localization lengths differ numerically from one another, but all of them remain short up to the numerically observed MBL transition, indicating stability of the MBL phase against isolated ergodic inclusions. We also show how these broad distributions may be extracted using interferometric probes such as double electronelectron resonance (DEER) and the statistics of local spin precession frequencies.
This paper reports the characterization and sorting of cells based on stiffness contrast. A microfluidic device with focusing and spacing control for stiffness based sorting of cells is designed, fabricated and demonstrated.
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