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Over the last decade, Organ-on-Chip (OoC) emerged as a promising technology for advanced in vitro models, recapitulating key physiological cues. OoC approaches tailored for cardiac tissue engineering resulted in a variety of platforms, some of which integrate stimulation or probing capabilities. Due to manual handling processes, however, a large-scale standardized and robust tissue generation, applicable in an industrial setting, is still out of reach. Here, we present a novel cell injection and tissue generation concept relying on spheroids, which can be produced in large quantities and uniform size from induced pluripotent stem cell-derived human cardiomyocytes. Hydrostatic flow transports and accumulates spheroids in dogbone-shaped tissue chambers, which subsequently fuse and form aligned, contracting cardiac muscle fibers. Furthermore, we demonstrate electrical stimulation capabilities by utilizing fluidic media connectors as electrodes and provide the blueprint of a low-cost, open-source, scriptable pulse generator. We report on a novel integration strategy of optical O2 sensor spots into resin-based microfluidic systems, enabling in situ determination of O2 partial pressures. Finally, a proof-of-concept demonstrating electrical stimulation combined with in situ monitoring of metabolic activity in cardiac tissues is provided. The developed system thus opens the door for advanced OoCs integrating biophysical stimulation as well as probing capabilities and serves as a blueprint for the facile and robust generation of high density microtissues in microfluidic modules amenable to scaling-up and automation.

In this work, we experimentally measured the absolute mass sensitivity of quartz crystal microbalance (QCM) resonators with one ring electrode on the sensing side and compared it to standard QCM resonators with disc electrodes on both sides using electrodeposition. This method allows to compare the absolute mass sensitivity of a ring electrode QCM and standard QCM resonators. The results showed that the average absolute mass sensitivity of a QCM resonator with a ring electrode on one side and a disc electrode on the other side is larger than the one of standard resonators with disc electrodes on both sides. If the ring electrode is facing the electrolyte, the absolute mass sensitivity is 10.28% higher, and for the disc electrode side it is still 5.33% higher. This shows that the ring electrode geometry improves the absolute mass sensitivity in comparison to a standard electrode structure, and therefore reveals a path to improve QCM detection sensitivity in electrochemical research.

A practical method for calculating the mass sensitivity of quartz crystal microbalance (QCM) resonators with ring-shaped Au electrodes on one side based on electrodeposition is presented in this communication. While for standard QCMs, an average mass sensitivity can be calculated despite its approximately Gaussian distribution, the mass sensitivity of QCMs with an asymmetrical electrode structure is difficult to calculate. However, non-standard electrode geometries might be beneficial for sensor applications especially in the area of electrochemistry. By measuring the resonance frequency change of a quartz crystal during deposition and applying Faraday’s law, we determined the mass sensitivity of QCM resonators with a ring electrode. We also studied the influence of the gold electrode thicknesses on the mass sensitivity of the ring-shaped and disc shaped electrodes. The experimental results showed that the mass sensitivity of the ring-shaped electrodes was 5%∼20% higher than those of the disc shaped electrodes. This method is practical and convenient for determining the mass sensitivity of the QCM with ring electrode, and it can be extended to measure QCMs with symmetrical and asymmetrical electrode structures. Such resonators with modified electrode structures may be of interest for studying electrochemical processes where a higher mass sensitivity is desirable.