Acoustic micropropulsors present great potential for microfluidic applications. The propulsion is based on encapsulated 20 μm bubbles excited by a contacless ultrasonic transducer. The vibrating bubbles then generate a powerful streaming flow, with speeds 1–100 mm s−1 in water, through the action of viscous stresses. In this paper we introduce a full toolbox of micropropulsors using a versatile three-dimensional (3D) microfabrication setup. Doublets and triplets of propulsors are introduced, and the flows they generate are predicted by a theoretical hydrodynamic model. We then introduce whole surfaces covered with propulsors, which we term active surfaces. These surfaces are excited by a single ultrasonic wave, can generate collective flows and may be harnessed for mixing purposes. Several patterns of propulsors are tested, and the flows produced by the two most efficient mixers are predicted by a simple theoretical model based on flow singularities. In particular, the vortices generated by the most efficient pattern, an L-shaped mixer, are analysed in detail.
Polydimethylsiloxane (PDMS) has been used in microfluidic systems for years, as it can be easily structured and its flexibility makes it easy to integrate actuators including pneumatic pumps. In addition, the good optical properties of the material are well suited for analytical systems. In addition to its positive aspects, PDMS is well known to adsorb small molecules, which limits its usability when it comes to drug testing, e.g., in organ-on-a-chip (OoC) systems. Therefore, alternatives to PDMS are in high demand. In this study, we use thermoplastic elastomer (TPE) films thermally bonded to laser-cut poly(methyl methacrylate) (PMMA) sheets to build up multilayered microfluidic devices with integrated pneumatic micro-pumps. We present a low-cost manufacturing technology based on a conventional CO2 laser cutter for structuring, a spin-coating process for TPE film fabrication, and a thermal bonding process using a pneumatic hot-press. UV treatment with an Excimer lamp prior to bonding drastically improves the bonding process. Optimized bonding parameters were characterized by measuring the burst load upon applying pressure and via profilometer-based measurement of channel deformation. Next, flow and long-term stability of the chip layout were measured using microparticle Image Velocimetry (uPIV). Finally, human endothelial cells were seeded in the microchannels to check biocompatibility and flow-directed cell alignment. The presented device is compatible with a real-time live-cell analysis system.
The placenta is a key embryonic structure that separates maternal and fetal blood systems. The barrier function of the human placenta is performed by villous trophoblasts, i.e. undifferentiated cytotrophoblasts and differentiated syncytiotrophoblats, whose maturation and function are influenced by wall shear stress (WSS) from the maternal blood circulation. Most in vitro placenta models rely on cyclic adenosine monophosphate inducer forskolin (FSK) to establish a placental syncytium. Here a trophoblastic BeWo cell line is used to systematically compare the effect of FSK treatment in static culture with WSS stimulation in a pumpless, recirculating organ‐on‐chip. It is shown that BeWo cells undergo a similar differentiation under WSS exposure to FSK treatment. A WSS of 0.1 dyn cm −2 leads to cell fusion, polarization, barrier functions, human chorionic gonadotropin (β‐hCG) secretion, and increased expression of key transporters. Moreover, WSS induces favorable changes in the levels of FMS‐like tyrosine kinase‐1 (FLT‐1) and Placental Growth Factor (PlGF) suggesting the development of a physiologically relevant placental syncytium‐on‐chip (PSoC) without the need for FSK. The platform is further expanded to a syncytiotrophoblast/endothelial co‐culture showing physiological vascular functions under WSS. The forskolin‐free PSoC presented here represents the first pumpless recirculating and scalable platform for physiological placental studies and drug testing.
We investigate the heterogeneous cavitation phenomenon in water when a spherical surface is abruptly separated from a nearby flat substrate, at a distance of approximately 10 nm. By tracking the surface separation using Newton ring positions, and capturing the bubble evolution with a high-speed camera on a microscope, we compare our experimental findings with hydrodynamic predictions at low Reynolds numbers. Upon upward movement of the spherical surface, the resulting bubble develops branched fingers through the Saffman–Taylor instability. Simultaneously, negative liquid pressures in the range $\sim$ 10 atm are observed. These large tension values occasionally lead to secondary nucleation events. The bubble sizes satisfy a predicted Family–Vicsek scaling law where the bubble area is proportional to the inverse bubble lifetime. The fact that creeping flow cavitation bubbles are more short-lived the larger they are separates them from bubbles that are governed by inertial dynamics.
Engineered heart tissues (EHTs), composed of human stem cell-derived cardiomyocytes and fibroblasts, have emerged as promising tools for disease modeling and drug discovery due to their ability to replicate aspects of the function and structure of the heart muscle. While bioimpedance and electrophysiology measurements are powerful tools for monitoring EHTs, these techniques can be challenging to perform due to the high conductivity of the surrounding cell medium. In this study, we explored the possibility of measuring bioimpedance and electrophysiology outside of the cell medium. To this end, we developed a platform that lifts EHTs from the culture medium during the measurements, thereby allowing the electrical current to flow directly through the tissues. The platform monitors contractility by fixed frequency impedance measurements, electrophysiology by field potential measurements, and structural changes through electrical impedance spectroscopy. Over two weeks of measurements, we observed increasing trends in contractility and field potential amplitudes, along with structural changes. No adverse effect on the EHTs were detected, ensuring their stability and viability throughout the monitoring process. Moreover, the impedance amplitude measured on the platform correlates with the contractile degree during drug experiments, serving as a reliable indicator of EHT functionality. Electrical stimulation with limited charge injection was also demonstrated. In conclusion, our platform offers a comprehensive and efficient method for monitoring EHTs and holds potential as a tool for cardiovascular disease modeling and drug screening.
This paper presents an innovative experimental setup that employs the principles of audio technology to subject adherent cells to rhythmic vertical vibrations. We employ a novel approach that combines three-axis acceleration measurements and particle tracking velocimetry to evaluate the setup’s performance. This allows us to estimate crucial parameters such as root mean square acceleration, fluid flow patterns, and shear stress generated within the cell culture wells when subjected to various vibration types. The experimental conditions consisted of four vibrational modes: No Vibration, Continuous Vibration, Regular Pulse, and Variable Pulse. To evaluate the effects on cells, we utilized fluorescence microscopy and a customized feature extraction algorithm to analyze the F-actin filament structures. Our findings indicate a consistent trend across all vibrated cell cultures, revealing a reduction in size and altered orientation (2D angle) of the filaments. Furthermore, we observed cell accumulations in the G1 cell cycle phase in cells treated with Continuous Vibration and Regular Pulse. Our results demonstrate a negative correlation between the magnitude of mechanical stimuli and the size of F-actin filaments, as well as a positive correlation with the accumulations of cells in the G1 phase of the cell cycle. By unraveling these analyses, this study paves the way for future investigations and provides a compelling framework for comprehending the intricate cellular responses to rhythmic mechanical stimulation.