摘要To enhance the efficiency of vaccine manufacturing,this study focuses on optimizing the microfluidic conditions and lipid mix ratios of messenger RNA-lipid nanoparticles(mRNA-LNP).Different mRNA-LNP formulations(n=24)were developed using an I-optimal design,where machine learning tools(XGBoost/Bayesian optimization and self-validated ensemble(SVEM))were used to optimize the process and predict lipid mix ratio.The investigation included material attributes,their respective ratios,and process attributes.The critical responses like particle size(PS),polydispersity index(PDI),Zeta potential,pKa,heat trend cycle,encapsulation efficiency(EE),recovery ratio,and encapsulated mRNA were eval-uated.Overall prediction of SVEM(＞97％)was comparably better than that of XGBoost/Bayesian opti-mization(＞94％).Moreover,in actual experimental outcomes,SVEM prediction is close to the actual data as confirmed by the experimental PS(94-96 nm)is close to the predicted one(95-97 nm).The other parameters including PDI and EE were also close to the actual experimental data.