Fabrication and Validation of a dual stimulation Organ-on-Chip

Abstract

This work presents the development and validation of a microfluidic Organ-on-Chip (OoC) platform designed to replicate complex in vivo mechanical and hydrodynamic stimuli. The device features two chambers within a PMMA structure, separated by a flexible silicone diaphragm. The upper chamber provides fluidic shear stress and nutrient circulation, while the lower chamber induces cyclic mechanical deformation. The silicone diaphragm was mechanically characterised using uniaxial and biaxial tests, ensuring optimal elasticity and robustness for its role in mimicking physiological conditions. Microfluidic testing validated the platform's functionality, demonstrating controlled and repeatable pulsatile pressure delivery. The diaphragm achieved a maximum deformation height of 0.32 mm under a flow rate of 200 μL/min, safely avoiding contact with the upper chamber, thus preserving cell viability. Numerical simulations using finite element analysis confirmed the diaphragm's structural integrity under operational stresses, with maximum stresses remaining well below rupture thresholds. The computationally obtained deformations were consistent with the mechanical stress levels typically experienced by various tissue types, making the device suitable for studying a wide range of physiological conditions and cellular responses. This dual-stimulation OoC bridges the gap between traditional 2D models and the complexity of human organ microenvironments, offering a robust system for simulating the mechanical and hydrodynamic conditions crucial for cellular behaviour. Future work will focus on integrating dynamic cell cultures to evaluate the device's potential in reproducing physiologically relevant environments