Miniaturized fiber-coupled microscope with cell-embedded hydrogel for odorant sensing

Cell-based biosensors employing olfactory receptor (OR)-expressing cells can detect odorant molecules with high selectivity and sensitivity; however, their translation into portable platforms remains limited by bulky optical systems and fixed configurations. Here, we present a compact and reconfigurable odorant sensing platform that integrates a miniature fluorescence microscope (MFM) with a fan-out optical fiber array to decouple the sensing site from the optical module. Each fiber tip is connected to a microwell filled with hydrogel-embedded OR-expressing cells, forming a sensing unit that transmits both excitation and emission light through the same optical path. A slit-integrated microwell design enables bubble-free hydrogel encapsulation, improving reproducibility and allowing reliable fluorescence measurements. Upon exposure to acetophenone, the platform exhibited dose-dependent fluorescence responses, with signal increases initiating at approximately 200 s and reaching a plateau around 600 s. Micromolar-level sensitivity was achieved, with a practical detection limit of 10 µM in the portable configuration. Furthermore, portable operation is demonstrated through direct odor detection at the air interface without liquid spillage, confirming the system’s stability during handling. The proposed platform combines excitation, readout, and multi-site sensing into a single compact device, enabling robust and quantitative biosensing. This approach offers a versatile and scalable platform for on-site chemical analysis, environmental monitoring, and further applications in biohybrid robotics. • ・Miniaturized fiber-coupled microscope enables compact and reconfigurable odorant sensing. • ・Cell-embedded hydrogel microwells at fiber tips achieve multiplexed fluorescence detection. • ・Optical and mechanical robustness allows stable on-site odor sensing under portable conditions.