Polystyrene nanoparticles (PS NPs) are widely used in cell-surface antigen detection, neuronal retrograde tracers and nanoparticle-cell interactions. In microfluidic size sorters, PS NPs are the most frequently-used virus and organelles models. Cells co-culture microfluidic chips and microfluidic size sorters generally have complex channel structures hardly be fabricated by silicon, glass and thermoplastics substrates (PMMA, PC, PS, etc.), however, could easily be fabricated by polydimethylsiloxane (PDMS). According to our findings, commercial PS NPs from dominating companies are adsorbed and absorbed in PDMS seriously, which seriously influence the accuracy of quantitative analysis. And to our best knowledges, methods specialized in these troublesome problems have not been reported yet. In this thesis, we focus on two convenient methods, dynamic surfactant coating and sol-gel coating, to minimize adsorption and absorption of PS NPs in PDMS. The effect of dynamic coating of several frequently-used surfactants (Pluronic® F-127, Pluronic® F108, trition X-100, tween 20 and sodium dodecyl sulfate (SDS)) were investigated and SDS revealed to be the most effective one and the coating concentration was optimized to be 1% (w/w). Solgel coating of silica, titanium and vanadium were also investigated respectively for their effect and vanadium coating performed best. Although adsorption and absorption of different sizes (45, 90, 220 and 370nm) of PS NPs in PDMS could be minimized significantly by simple using of 1% SDS coating or vanadium coating, the problems could not be solved completely. Thus, a combined use of vanadium coating and 1% SDS dynamic coating was investigated and the effect improved significantly and almost prevented adsorption and absorption of PS NPs in PDMS. The combined use of two modifications provide an accessible solution for the application of PS NPs in PDMSbased microfluidic chips. Furthermore, biocompatibility of PDMS was significantly improved after vanadium coating or titanium coating, providing more choose to modify PDMS-based microfluidic chips to conduct biology experiments.