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High-quality baijiu yeast – modified Sporidiobolus johnsonii A (MSJA) suffers from the problem of weak vitality, thus failing to combine high efficiency and high survival rate drying. Therefore, in this study, we firstly designed a real-time sampling experiment of MSJA spray drying process, and based on this, we established a New CFD model (N-CFD model) that can accurately simulate the variation of the spray drying process of microorganisms such as MSJA. Then, a new spray drying air inlet mechanism of "high-temperature cyclone in the center L-type guide plate + medium-temperature laminar flow in the peripheral holes and slots" was invented. Finally, the parametric scanning simulation was carried out to optimize the flow angle θ of the L-type guide plate using the N-CFD model. The results show that, firstly, the N-CFD model can accurately simulate the temperature distribution (P1 = 0.05) and the motion of drying particles in the drying tower. Secondly, the optimized new air inlet mechanism with the L-type guide plate flow angle θ = 47° can even out the temperature and particle distribution in the drying tower, which meets the "two-stage theory of spray drying." Finally, under the premise of ensuring the drying efficiency, the survival rate of MSJA spray drying was increased from 42.6% to 82.24%, which achieved the objectives of low sticking wall, high efficiency and high survival rate of spray drying MSJA. [ABSTRACT FROM AUTHOR]