Novel monodisperse cationic pH-responsive microcapsules are successfully prepared using oil-in-water-in-oil double emulsions as templates by a microfluidic technique in this study. With the use of a double photo-initiation system and the adjustment of pH value of the monomer solution, cross-linked poly(N,N-dimethylaminoethyl methacrylate) (PDM) microcapsules with good sphericity and monodispersity can be effectively fabricated. The obtained microcapsule membranes swell at low pH due to the protonation of -N(CH3)(2) groups in the cross-linked PDM networks. The effects of various preparation parameters, such as pH of the aqueous monomer fluid, concentration of cross-linker, concentration of monomer N,N-dimethylaminoethyl methacrylate (DM) and addition of copolymeric monomer acrylamide (AAm), on the pH-responsive swelling characteristics of PDM microcapsules are systematically studied. The results show that, when the PDM microcapsules are prepared at high pH and with low cross-linking density and low DM monomer concentration, they exhibit high pH-responsive swelling ratios. The addition of AAm in the preparation decreases the swelling ratios of PDM microcapsules. The external temperature has hardly any influence on the swelling ratios of PDM microcapsules when the external pH is less than 7.4. The prepared PDM microcapsules with both biocompatibility and cationic pH-responsive properties are of great potential as drug delivery carriers for tumor therapy. Moreover, the fabrication methodology and results in this study provide valuable guidance for preparation of core-shell microcapsules via free radical polymerization based on synergistic effects of interfacial initiation and initiation in a confined space. (C) 2011 Elsevier Inc. All rights reserved.