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The organosilicon reagent methacryloxypropyltrimethoxysilane was introduced into the polymer framework as a copolymerization monomer, and the crosslinking degree of the microspheres was improved by the hydrolysis\u2010condensation reaction of siloxanes. The synthesized hybrid microspheres have good mechanical strength as well as low swelling, with swelling propensity values of 0.167 and 0.348 in methanol and acetonitrile, respectively. Hybrid microspheres modified with cysteine have a hydrophilic interaction chromatography\/reversed\u2010phase liquid chromatography mixed\u2010mode retention mechanism. 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