Abstract
Various gastrointestinal disorders have been linked to gut microbiome dysbiosis, as it plays a critical role in immune regulation, metabolism, nutrient digestion, and pathogen suppression. However, the microbiome’s spatial variability across gastrointestinal segments and its intra- and interindividual differences complicate its study and clinical interpretation. While fecal DNA analysis is commonly used, stool samples only capture an accumulated signal and miss the spatial dynamics of microbial populations. To address this, we propose a modular sampling capsule capable of wirelessly collecting liquid. The capsule consists of two main modules: (i) an actuator module integrating a polymer-based microfluidic system with meltable wax-based opening valve, screen-printed microheater, cellulose membrane-based closing valve, evacuated sampling chamber with dried sample preservative material, filter membrane (size exclusion 150 μm), and sample extraction channel; and (ii) a control electronic module with communication, localization, and power supply units. The actuator module was validated in vitro using a diluted stool simulant (330 mg/mL) and an uncleaned porcine intestine. The opening valve activated within 3.6 ± 0.5 s at 120 ± 10 mA and 0.8 V. The sample was then filtered and aspirated into the sampling chamber within 1–2 s, and the closing valve sealed the inlet completely within 10 min. We overcame design, material, and fabrication challenges to construct an actuator module that functions effectively in liquids with variable physicochemical conditions (pH, chemical composition, viscosity, and particle size). These results demonstrate the feasibility of a controlled, segment-specific intestinal sampling capsule, representing a step towards precise and accurate microbiome profiling. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10544-026-00802-4.