High-throughput synthesis of liposome using an injection-molded plastic micro-fluidic device

Abstract

For mass production of liposomes, we designed a plastic micro-channel device on the basis of 5 μm of micro-nozzle array forming T-junction with 100 μm depth of micro-channel. A micro-channel unit for synthesizing liposomes consisted of two micro-nozzle arrays for mixing two solutions as well as delivery and recovery channels for supplying solutions and collecting liposome suspension. The number of micro-nozzles was approximately 2400 for a micro-channel unit, and seven units were applied independently on a micro-channel plate. The plastic micro-channel plate was injection-molded for mass production using a micro-channel stamper previously fabricated by UV lithography and nickel electroforming process. A plastic cover plate with seven pairs of inlet and outlet ports was machined by mechanical milling and drilling and was assembled with a micro-channel plate using a holder to form a liposome synthesizing device. Flow and mixing of solutions in the micro-channels were tested using colored water to check the micro-fluidic characteristics of the device. Finally, a L-α-phosphatidylcholine (SOY PC) liposome was synthesized using EtOH solution of SOY PC (95%) and saline (0.85% NaOH solution) to find that the liposomes were around 230 and 260 nm in diameter, depending on the flow rate of the lipid solution.