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Ultrasound application may be used to drive the entrance of plasmid DNA in vitro and in vivo. For efficient transfection, air bubble containing contrast agents are usually used. We described here a new method to produce air bubble containing lipid/DNA lipoplexes. The transfection efficiencies using these lipoplexes were examined in vitro on SPCA-1 cells. The cells were irradiated with 1 MHz ultrasound for various time durations. Parameters such as ultrasound intensity, sonication time, and ultrasound frequency used were evaluated for improved transfection.