Objectives To establish an automated high-throughput mimic perfusion scale-down model (SDM) in ambr(R) 15 system. Results An optimized SDM for mimic perfusion was developed in ambr(R) 15 system. Cell retention in ambr(R) 15 was realized by sedimentation and supernatant removal with a retention rate > 95%. Although the SDM couldn't reach the viable cell density (VCD) at a bench scale bioreactor (BR), it maintained VCD at approximately 30 x 10(6) cells/mL with a cell bleeding rate estimated theoretically and predicted the cell specific perfusion rate (CSPR). A base-feeding strategy was developed to alleviate the pH drop during sedimentation which would adversely have an impact on cell growth, and showed an apparent cell viability improvement from 79.6% (control) to 90.1% on Day 18. The optimized SDM for mimic perfusion was employed for media screening in two cell lines. Conclusions A small-scale high-throughput perfusion model in ambr(R) 15 was developed, optimized to improve cell viability, and as a result, utilized for media screening in two cell lines.