Microphysiological systems (MPS) are advanced in vitro platforms engineered to replicate in vivo conditions for studying human biology, disease mechanisms, and drug responses with greater physiological relevance. Fluorescence sensing is widely used as a functional readout in MPS due to its high sensitivity, selectivity, and stability. However, conventional fluorescence sensing systems often rely on bulky instrumentation with limited integration, which restricts continuous in situ monitoring, scalable high-throughput analysis, and spatially resolved investigation in multi-organ-on-a-chip models. To address these limitations, we present a highly miniaturized, fully integrated optical system with a 1 mm² footprint, enabling continuous in situ fluorescence monitoring of three-dimensional microtissues in close proximity. The system integrates microscale illumination and sensing units for fluorescence excitation and selective detection, an optical element for guided light propagation, and a microcage for mechanical confinement of microtissues. To demonstrate its capabilities, we integrated the miniaturized optical system with an MPS-relevant platform to monitor fluorescence signals in transgenic mouse pancreatic islets expressing genetically encoded calcium indicators. The integrated platform enables real-time, continuous monitoring of islet responses to potassium chloride stimulation and tracking of calcium oscillations for over two hours, providing valuable information about the functional status of the pancreatic islets. Our work enhances the analytical capabilities of MPS through the integration of miniaturized on-chip quantitative assessment tools, enabling precise, in situ, and continuous monitoring of biological activities in close proximity.

Hybridizing biological cells with man-made sensors enable the detection of a wide range of weak physiological responses with high specificity. The anterior chamber of the eye (ACE) is an ideal transplantation site due to its ocular immune privilege and optical transparency, which enable superior non-invasive longitudinal analyses of cells and microtissues. Engraftment of biohybrid microstructures in the ACE might, however, be affected by the pupillary response and dynamics. Here, sutureless transplantation of biohybrid microstructures, 3D printed in IP-Visio photoresin, containing a precisely localized pancreatic islet to the ACE of mice is presented. The biohybrid microstructures allow mechanical fixation in the ACE, independent of iris dynamics. After transplantation, islets in the microstructures successfully sustain their functionality for over 20 weeks and become vascularized despite physical separation from the vessel source (iris) and immersion in a low-viscous liquid (aqueous humor) with continuous circulation and clearance. This approach opens new perspectives in biohybrid microtissue transplantation in the ACE, advancing monitoring of microtissue-host interactions, disease modeling, treatment outcomes, and vascularization in engineered tissues.

Advanced in vitro cell culture systems or microphysiological systems (MPSs), including microfluidic organ‐on‐a‐chip (OoC), are breakthrough technologies in biomedicine. These systems recapitulate features of human tissues outside of the body. They are increasingly being used to study the functionality of different organs for applications such as drug evolutions, disease modeling, and precision medicine. Currently, developers and endpoint users of these in vitro models promote how they can replace animal models or even be a better ethically neutral and humanized alternative to study pathology, physiology, and pharmacology. Although reported models show a remarkable physiological structure and function compared to the conventional 2D cell culture, they are almost exclusively based on standard passive polymers or glass with none or minimal real‐time stimuli and readout capacity. The next technology leap in reproducing in vivo‐like functionality and real‐time monitoring of tissue function could be realized with advanced functional materials and devices. This review describes the currently reported electronic and optical advanced materials for sensing and stimulation of MPS models. In addition, an overview of multi‐sensing for Body‐on‐Chip platforms is given. Finally, one gives the perspective on how advanced functional materials could be integrated into in vitro systems to precisely mimic human physiology.