Proton exchange membrane fuel cells (PEMFCs) offer a promising pathway to decarbonize regional aviation. However, the internal heat and mass transport mechanisms high-power PEMFC stacks under flight conditions remain insufficiently studied. To address this, this paper develops a novel multi-methodological framework that integrates a flow network model (FNM) of a shared-manifold configuration parameterized by CFD analysis of a novel large-scale modular flow field, a 1D PEMFC multi-physics model resolving core electrochemical phenomena, and key balance-of-plant (BoP) subsystems. This integrated approach establishes a scalable, minute-scale, physics-based modeling framework for 400-kW class stack performance prediction, calibrated against multi-scale experimental data and capable of capturing water-thermal-gas distributions from stack to individual cells. A multi-objective optimization using the NSGA-II algorithm is then applied to a specific flight mission to enhance operational uniformity and reduce hydrogen consumption. The results reveal that altitude-induced performance degradation above 4000 m is primarily driven by severe reactant maldistribution, leading to a 50 mV voltage loss increase and a tripling of the voltage deviation rate (CV) at 8000 m. As transitioning from a challenging water-thermal condition and maldistributed gas distribution state at take-off to a stable state at cruise, the high-load state result in an ohmic loss that is nearly double that of the cruise phase. Optimization significantly improves stack performance, achieving 13.2 % reduction in CV and 26.9 % and 17.2 % increases in oxygen and hydrogen concentrations at the catalytic layers during take-off phase. System-level analysis confirms hydrogen savings of 0.727 g/s per stack during cruise, resulting in a total 1569.7 L reduction in storage volume per 2-h flight for a 72-seat regional aircraft. This study establishes a high-fidelity, multi-scale modeling and optimization platform that bridges cell-to-stack level water-thermal transport mechanisms with system level design, providing critical insights and tools for developing next-generation aviation fuel cell systems.
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