A Microfluidic Micropipette Aspiration Device to Study Single-Cell Mechanics Inspired by the Principle of Wheatstone Bridge.

The biomechanical properties of single cells show great potential for early disease diagnosis and effective treatments. In this study, a microfluidic device was developed for quantifying the mechanical properties of a single cell. Micropipette aspiration was integrated into a microfluidic device that mimics a classical Wheatstone bridge circuit. This technique allows us not only to effectively alter the flow direction for single-cell trapping, but also to precisely control the pressure exerted on the aspirated cells, analogous to the feature of the Wheatstone bridge that can precisely control bridge voltage and current. By combining the micropipette aspiration technique into the microfluidic device, we can effectively trap the microparticles and Hela cells as well as measure the deformability of cells. The Young's modulus of Hela cells was evaluated to be 387 ± 77 Pa, which is consistent with previous micropipette aspiration studies. The simplicity, precision, and usability of our device show good potential for biomechanical trials in clinical diagnosis and cell biology research.

A microfluidic device with spatiotemporal wall shear stress and ATP signals to investigate the intracellular calcium dynamics in vascular endothelial cells.

Intracellular calcium dynamics plays an important role in the regulation of vascular endothelial cellular functions. In order to probe the intracellular calcium dynamic response under synergistic effect of wall shear stress (WSS) and adenosine triphosphate (ATP) signals, a novel microfluidic device, which provides the adherent vascular endothelial cells (VECs) on the bottom of microchannel with WSS signal alone, ATP signal alone, and different combinations of WSS and ATP signals, is proposed based upon the principles of fluid mechanics and mass transfer. The spatiotemporal profiles of extracellular ATP signals from numerical simulation and experiment studies validate the implementation of our design. The intracellular calcium dynamics of VECs in response to either WSS signal or ATP signal alone, and different combinations of WSS and ATP signals have been investigated. It is found that the synergistic effect of the WSS and ATP signals plays a more significant role in the signal transduction of VECs rather than that from either WSS signal or ATP signal alone. In particular, under the combined stimuli of WSS and ATP signals with different amplitudes and frequencies, the amplitudes and frequencies of the intracellular Ca2+ dynamic signals are observed to be closely related to the amplitudes and frequencies of WSS or ATP signals.

A Y-Shaped Microfluidic Device to Study the Combined Effect of Wall Shear Stress and ATP Signals on Intracellular Calcium Dynamics in Vascular Endothelial Cells.

The intracellular calcium dynamics in vascular endothelial cells (VECs) in response to wall shear stress (WSS) and/or adenosine triphosphate (ATP) have been commonly regarded as an important factor in regulating VEC function and behavior including proliferation, migration and apoptosis. However, the effects of time-varying ATP signals have been usually neglected in the past investigations in the field of VEC mechanobiology. In order to investigate the combined effects of WSS and dynamic ATP signals on the intracellular calcium dynamic in VECs, a Y-shaped microfluidic device, which can provide the cultured cells on the bottom of its mixing micro-channel with stimuli of WSS signal alone and different combinations of WSS and ATP signals in one single micro-channel, is proposed. Both numerical simulation and experimental studies verify the feasibility of its application. Cellular experimental results also suggest that a combination of WSS and ATP signals rather than a WSS signal alone might play a more significant role in VEC Ca2+ signal transduction induced by blood flow.