Julien Aubert

Abstract Human complex in vitro models (CIVMs) have demonstrated remarkable potential to study tissue development, physiology and disease at high-throughput. To effectively employ these miniaturized systems in translational preclinical research, their in-depth benchmarking is pivotal. Histology has been the core of tissue characterization for centuries and the foundation of spatial phenotyping. However, standard histology workflows are inherently low-throughput and centered on large tissue pieces. This does not match the high sample volumes and small sample sizes in CIVM research. Here, we introduce a holistic ‘histo-workflow’, utilizing 3D-printed histomolds that facilitate co-planar embedding of CIVMs at high-throughput, resulting in up to 48 samples in one section. We developed a variety of model-specific histomold designs that enable spatially controlled histological sectioning and downstream analyses. We describe these workflows, including mold generation, highplex staining and image analysis, and exemplify their application to histological analyses of various CIVMs. Altogether, the histomolds introduced here afford opportunities for CIVM processing and analysis, while significantly reducing labor and reagent resources, thereby democratizing high-throughput CIVM in histopathology.

Historically, technology has been central to new discoveries in biology and progress in medicine. Among various technologies, microtechnologies, in particular, have had a prominent role in the revolution experienced by the life sciences in the last few decades, which will surely continue in the years to come. In this Perspective, we illustrate how microtechnologies, with a focus on microfluidics, have evolved in trends/waves to tackle the boundary of knowledge in the life sciences. We provide illustrative examples of technology-enabled biological breakthroughs and their current and future use in clinics. Finally, we take a closer look at the translational process to understand why the incorporation of new micro-scale technologies in medicine has been comparatively slow so far.

Gill, Muenchau et al. demonstrated the presence of key drug transporters and metabolic enzymes in an engineered intestinal barrier model, and combined the system with in silico modeling to simultaneously capture drug permeability and metabolism.

10.1063/5.0047196.1 Historically, technology has been central to new discoveries in biology and progress in medicine. Among various technologies, microtechnologies, in particular, have had a prominent role in the revolution experienced by the life sciences in the last few decades, which will surely continue in the years to come. In this Perspective, we illustrate how microtechnologies, with a focus on microfluidics, have evolved in trends/waves to tackle the boundary of knowledge in the life sciences. We provide illustrative examples of technology-enabled biological breakthroughs and their current and future use in clinics. Finally, we take a closer look at the translational process to understand why the incorporation of new micro-scale technologies in medicine has been comparatively slow so far.