In an ongoing effort to increase product yields of CHO cells, a 3D-printed microfluidic spiral separator for plug and play cell retention was combined with a small-scale bioreactor system. In addition, this system includes automatic flushing, web-based control, and a mobile status notification. A proof-of-concept cultivation over 530 h at viable cell concentrations between 10-17 x 106 cells/mL in a hybrid mode (with alternating cell retention and cell bleed phases) successfully reduced both shear stress and microfluidic channel blockage. In addition to a retention efficiency of almost 100 %, this set-up also increased cell viability within the bioreactor by separating dead cells and cell debris into the cell-free fraction. Moreover, no retention of the product was detected.