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Simple and rapid prototyping of microfluidic devices is highly desirable for fundamental academic research,which allows researchers to focus on device application instead of fabrication [1].Although soft lithography based on poly(dimethylsiloxane)(PDMS)has enabled the rapid prototyping of numerous types of microfluidic devices,it still subject to some limitations such as the requirement of expensive "clean rooms" and photolithographic equipment,and time-consuming master fabrication process.To rapidly and cheaply prototype microfluidic devices at research laboratories,we developed a cost-effective and simple method to fabricate PDMS-based microfluidic devices by combining wax micromilling with replica moulding technology.The basic fabrication process is described in Figure 1,which consists of four main steps:(ⅰ)fabrication of a wax-based female mold using micromilling,(ⅱ)reduction of surface roughness of the micromilled channels using gas-blowing-assisted PDMS coating,(ⅲ)fabrication of an epoxy-based male mold using polymer casting,and(iv)fabrication of the PDMS-based microfluidic device using soft lithography.The geometry and quality of the master molds and the PDMS microfluidic channels are characterized using SEM and optical microscopy.This method provides the widest range of feature capabilities with the least added process complexity.Particularly,this method is capable of making complex three-dimensional(3D)features that may be impractical or unfeasible with other methods.This is demonstrated by the microchannels such as stepped depth,graded depth,semicircular cross-section,and trapezoid cross-section channels showed in Figure 2.To demonstrate the feasibility of the proposed microfabrication technique,a microfluidic droplet generator was fabricated and tested [2].Monodispersed droplets were successfully generated in the as-fabricated droplet generator(Figure 3).This approach offers an easy,flexible and rapid prototyping of microfluidic and lab-on-a-chip devices to users without expertise in microfabrication.In addition,micromilling can also be used to fabricate multi-level microfluidic structures during the same milling procedure simply by typing the parameters into the control system,which allows combining more functions and applications into the microfluidic device for integrating microfluidic system.