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Over the past few years, several studies have shown that the gastrointestinal microbiome plays a key role in the processing of exogenous pharmaceutical compounds [1]. Additionally, previous work on the gut-liver axis has shown that the interplay between the intestinal microbiome, the gut barrier and the liver is fundamental for regulating these drug metabolism processes [2]. Disruption of these processes may lead to gut barrier dysfunction. This might result in the induction of inflammatory signaling pathways in the liver and ultimately modify drug metabolism by hepatocytes. Modeling the highly variable luminal gut environment and understanding how gut microbes can modulate drug availability or induce liver toxicity remains a challenge. Hence, there is a significant need to develop new platforms that enable the co-culture of human and microbial cells in a patient-specific manner. Microfluidics-based technologies such as organ-on-chips (OoC) could overcome current challenges in drug toxicity assessment assays as these technologies are designed to be more physiologically relevant than conventional in vitro and in vivo models. The main objective of this work is to interconnect our microfluidics-based Human Microbial Crosstalk (HuMiX) model [3] with the Dynamic42 liver-on-chip [4] in order to create a stem-cell based multi-organ platform to predict the effect of the gut microbiome on pharmacokinetics [5]. The improvement of current OoC platforms could lead to a powerful alternative to stepwise replace the use of animal experimentation regarding the microbiome and its role on drug metabolization for individual patients. [1] Zimmermann M et al., Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 2019;570:462–7. [2] Khalsa J et al., Omics for Understanding the Gut‐Liver‐Microbiome Axis and Precision Medicine. Clin Pharm Drug Dev 2017;6:176–85. [3] Shah, P.et al. A microfluidics-based in vitro model of the gastrointestinal human–microbe inte

Integration of sensors in OoC is advantageous to monitor cell proliferation and differentiation, for example via TEER measurements. The established method to pattern electrical sensors is thin-film deposition of metals such as Au or Pt, often structured on stiff substrates like glass or polycarbonate. There is however a need to be able to define electrodes on flexible substrates for integration in more complex OoCs including multiple layers, such as the HuMiX system [1]. Handling and metal deposition on thin flexible substrates is challenging, due to poor adhesion under bending stress. Here, we present a robust method where electrodes can be patterned on flexible substrates for OoC integration. Using polyimide substrate and carrier foils allows for integration of electrodes also into system designs that are themselves too thick to fit into common sputter machines. This method also allows for integration of electrodes over uneven surfaces and steps, that are otherwise difficult to handle. [1] P. Shah et al., “A microfluidics-based in vitro model of the gastrointestinal human–microbe interface,” Nat. Commun., vol. 7, no. 1, p. 11535, Sep. 2016.

Microfluidic chips offer many benefits for cell studies, including an accurate spatial and temporal control over the growth conditions1. Despite the large expansion of microfluidics in biological applications2, there have been only a few developments of devices to simplify microfluidic chip handling and imaging. Here, we present a carrier of well-plate format with integrated cell media recirculation and heating systems to provide a stable environment for the cell culture during the imaging outside the incubator. Moreover, the absence of external tubing reduces the risk of contamination and bubble formation during the carrier transfers and reagent injections enabling long-term experiment monitoring. Our system was validated by repeatedly (day 1, 3, 7 and 10) taking the cultured mouse endothelial cells (bEnd.3) out of the incubator for imaging.

Organ-on-chip systems are promising new in vitro research tools in medical, pharmaceutical, and biological research. Their main benefit, compared to standard cell culture platforms, lies in the improved in vivo resemblance of the cell culture environment. A critical aspect of these systems is the ability to monitor both the cell culture conditions and biological responses of the cultured cells, such as proliferation and differentiation rates, release of signaling molecules, and metabolic activity. Today, this is mostly done using microscopy techniques and off-chip analytical techniques and assays. Integrating in situ analysis methods on-chip enables improved time resolution, continuous measurements, and a faster read-out; hence, more information can be obtained from the developed organ and disease models. Integrated electrical, electrochemical, and optical sensors have been developed and used for chemical analysis in lab-on-a-chip systems for many years, and recently some of these sensing principles have started to find use in organ-on-chip systems as well. This perspective review describes the basic sensing principles, sensor fabrication, and sensor integration in organ-on-chip systems. The review also presents the current state of the art of integrated sensors and discusses future potential. We bring a technological perspective, with the aim of introducing in-line sensing and its promise to advance organ-on-chip systems and the challenges that lie in the integration to researchers without expertise in sensor technology.

This work presents an acoustic trap with integrated thin film sensors to monitor temperature variations during operation. The acoustic trap is wet-etched in glass with a thermally bonded glass lid and the thin-film sensors are integrated during fabrication. We evaluated the performance of the integrated temperature sensors and measured a temperature sensitivity of +/- 0.01 degrees C and confirmed that the read-out of the thin film sensors was not affected neither by the ionic conductivity of the solution nor the addition of microparticles into the acoustic trap. From the experiments we observed a temperature increase of the acoustic trap during operation as a result of the dissipative heating of the the piezoelectric element used to actuate the trap. We also showed that when external convective cooling was applied to the system, the temperature increase of the acoustic trap was higher than the temperature increase of the piezoelectric element itself. This shows the importance of using integrated temperature sensors in acoustic trapping to monitor the local environmental conditions.