The new NMPC platform simultaneously regulates feed, bleed and harvest streams in a perfusion bioreactor, delivering a 68 % increase in product titer while keeping the culture’s viable cell density at or above 95 %.
The controller uses a moving‑horizon estimator to infer unmeasured process states and enforce biological constraints in real time. After the process stabilises, an economic NMPC (ENMPC) mode takes over, continuously calculating optimal operating conditions and eliminating the need for ad‑hoc damping functions or frequent weight retuning that plague standard ENMPC formulations.
According to Mahshad Valipour, PhD, senior research scientist, and Christopher McCready, head of product innovation at Sartorius, the combined multifunction NMPC and economic mode enables “seamless transition between operating modes without controller switching or reformulation,” allowing manufacturers to shift objectives on‑the‑fly between stable operation and economic optimisation.
The team validated the approach with digital‑twin experiments and real‑world runs, finding that online and inline measurements of viable cell density, viability and dead‑cell density matched the model’s predictions. Even when deliberately introducing a significant plant‑model mismatch, the system remained stable throughout the perfusion run.
The study suggests that advanced automation strategies like this NMPC framework can resolve long‑standing hurdles in continuous CHO perfusion, making the process more predictable, efficient and adaptable for bioprocessors seeking higher yields and tighter control over inhibitory biomaterial accumulation.