A novel method for combinatorial synthesis and screening of uniform-size molecularly imprinted microspheres using a microfluidic device is presented, in which a new microfluidic device containing twelve pairs of shape microchannels is designed to produce droplets and imprinted microspheres via controlled suspension polymerization. This technique combines molecular imprinting and microfluidic device with the combinatorial chemical approach, allowing rapid screening and optimization of uniform imprinted microspheres. On the example of chloramphenicol (CAP), the imprinted microspheres of CAP were prepared by a combinatorial approach using water with 1.5% polyvinyl alcohol as continuous phase, and ethyl acetatechloroform (4:1, v/v) as porogenic solvents. Functional monomers methacrylic acid (MAA), 4-vinylpyridine or acrylamide were screened, and the molar ratio of template molecule to functional monomer was optimized. The results indicate that MAA is the best functional monomer for imprinting of CAP, and when the molar ratio of CAP to MAA is 1:5, the imprinted microspheres exhibit the best imprinting performance, and have good monodispersity and selectivity. This combinatorial protocol is well suited for fast and efficient screening and optimization of synthesis for uniform imprinted microspheres because 12 kinds of imprinting conditions can be performed simultaneously in this microfluidic device. POLYM. ENG. SCI., 2012. (C) 2012 Society of Plastics Engineers