A micro-UV bio-fluorescence sensor was developed to detect primary biological aerosols including bacteria, bacterial spores, fungal spores, pollens, viruses, algae, etc. In order to effectively detect the bio-particles in a micro-UV bio-fluorescence sensor, numerical calculations were performed to adjust for appropriate flow conditions of the sensor by regulating the sample aerosols and sheath flow. In particular, a CFD-based model of hydrodynamic processes was developed by computing the trajectory of particles using commercially available ANSYS CFX-14 software and the Lagrangian tracking model. The established model was evaluated with regard to the variation of sheath flow rate and particle size. Results showed that the sheath flow was changed rapidly at the end of nozzle tip, but the sample particles moved near the center of aerosol jet for aerodynamic focusing with little deviation from the axis.