Microphysiological systems hold the promise to increase the predictive and translational power of in vitro substance testing owing to their faithful recapitulation of human physiology. However, the implementation of academic developments in industrial settings remains challenging. We present an injection-molded microfluidic microtissue (MT) culture chip that features two channels with 10 MT compartments each and that was designed in compliance with microtiter plate standard formats. Polystyrene as a chip material enables reliable, large-scale production and precise control over experimental conditions due to low adsorption or absorption of small, hydrophobic molecules at or into the plastic material in comparison with predecessor chips made of polydimethylsiloxane. The chip is operated by tilting, which actuates gravity-driven flow between reservoirs at both ends of every channel, so that the system does not require external tubing or pumps. The flow rate can be modulated by adjusting the tilting angle on demand. The top-open design of the MT compartment enables efficient MT loading using standard or advanced pipetting equipment, ensures oxygen availability in the chip, and allows for high-resolution imaging. Every channel can be loaded with up to 10 identical or different MTs, as demonstrated by culturing liver and tumor MTs in the same medium channel on the chip.

The multifactorial nature of inflammatory bowel disease (IBD) necessitates reliable and practical experimental models to elucidate its etiology and pathogenesis. To model the intestinal microenvironment at the onset of IBD in vitro, it is important to incorporate relevant cellular and noncellular components before inducing stepwise pathogenic developments. A novel intestine‐on‐chip system for investigating multiple aspects of IBD's immunopathogenesis is presented. The system includes an array of tight and polarized barrier models formed from intestinal epithelial cells on an in‐vivo‐like subepithelial matrix within one week. The dynamic remodeling of the subepithelial matrix by cells or their secretome demonstrates the physiological relevance of the on‐chip barrier models. The system design enables introduction of various immune cell types and inflammatory stimuli at specific locations in the same barrier model, which facilitates investigations of the distinct roles of each cell type in intestinal inflammation development. It is showed that inflammatory behavior manifests in an upregulated expression of inflammatory markers and cytokines (TNF‐α). The neutralizing effect of the anti‐inflammatory antibody Infliximab on levels of TNF‐α and its inducible cytokines could be explicitly shown. Overall, an innovative approach to systematically developing a microphysiological system to comprehend immune‐system‐mediated disorders of IBD and to identify new therapeutic strategies is presented.

In vitro screening methods for compound efficacy and toxicity to date mostly include cell or tissue exposure to preset constant compound concentrations over a defined testing period. Such concentration profiles, however, do not represent realistic in vivo situations after substance uptake. Absorption, distribution, metabolism and excretion of administered substances in an organism or human body entail gradually changing pharmacokinetic concentration profiles. As concentration profile dynamics can influence drug effects on the target tissues, it is important to be able to reproduce realistic concentration profiles in in vitro systems. We present a novel design that can be integrated in tubing-free, microfluidic culture chips. These chips are actuated by tilting so that gravity-driven flow and perfusion of culture chambers can be established between reservoirs at both ends of a microfluidic channel. The design enables the realization of in vivo-like substance exposure scenarios. Compound gradients are generated through an asymmetric Y-junction of channels with different hydrodynamic resistances. Six microtissues (MTs) can be cultured and exposed in compartments along the channel. Changes of the chip design or operation parameters enable to alter the dosing profile over a large range. Modulation of, e.g., the tilting angle, changes the slope of the dosing curves, so that concentration curves can be attained that resemble the pharmacokinetic characteristics of common substances in a human body. Human colorectal cancer (HCT 116) MTs were exposed to both, gradually decreasing and constant concentrations of Staurosporine. Measurements of apoptosis induction and viability after 5 h and 24 h showed different short- and long-term responses of the MTs to dynamic and linear dosing regimes

Studying and understanding of tissue and disease mechanisms largely depend on the availability of suitable and representative biological model systems. These model systems should be carefully engineered and faithfully reproduce the biological system of interest to understand physiological effects, pharmacokinetics, and toxicity to better identify new drug compounds. By relying on microfluidics, microphysiological systems (MPSs) enable the precise control of culturing conditions and connections of advanced in vitro 3D organ models that better reproduce in vivo environments. This review focuses on transferable in vitro organ models and integrated MPSs that host these transferable biological units and enable interactions between different tissue types. Interchangeable and transferrable in vitro organ models allow for independent quality control of the biological model before system assembly and building MPS assays on demand. Due to the complexity and different maturation times of individual in vitro tissues, off‐chip production and quality control entail improved stability and reproducibility of the systems and results, which is important for large‐scale adoption of the technology. Lastly, the technical and biological challenges and open issues for realizing and implementing integrated MPSs with transferable in vitro organ models are discussed.

Microfluidic-drop networks consist of several stable drops—interconnected through microfluidic channels—in which organ models can be cultured long-term. Drop networks feature a versatile configuration and an air–liquid interface (ALI). This ALI provides ample oxygenation, rapid liquid turnover, passive degassing, and liquid-phase stability through capillary pressure. Mathematical modeling, e.g., by using computational fluid dynamics (CFD), is a powerful tool to design drop-based microfluidic devices and to optimize their operation. Although CFD is the most rigorous technique to model flow, it falls short in terms of computational efficiency. Alternatively, the hydraulic–electric analogy is an efficient “first-pass” method to explore the design and operation parameter space of microfluidic-drop networks. However, there are no direct electric analogs to a drop, due to the nonlinear nature of the capillary pressure of the ALI. Here, we present a circuit-based model of hanging- and standing-drop compartments. We show a phase diagram describing the nonlinearity of the capillary pressure of a hanging drop. This diagram explains how to experimentally ensure drop stability. We present a methodology to find flow rates and pressures within drop networks. Finally, we review several applications, where the method, outlined in this paper, was instrumental in optimizing design and operation.