Inline MIR Spectroscopy as PAT for continuous downstream processing

Continuous biomanufacturing needs rapid, trustworthy feedback to keep critical process parameters and quality attributes within target ranges. In ultrafiltration/diafiltration (UF/DF), concentration and excipient levels are still frequently confirmed by offline analytics, creating delays that hinder control.
We introduce Monipa, a modular mid-infrared (MIR) spectroscopy platform for inline concentration analytics. A customizable single-use flow cell enables straightforward integration into disposable set-ups and supports both inline and at-line measurements.
Quantification is achieved with a practical one-point calibration, avoiding large training datasets while remaining compatible with subsequent chemometric model development. With acquisition times around 10 s, Monipa delivers near-real-time readouts suitable for process steering. In UF/DF case studies, Monipa tracked protein concentrations up to 250 g/L together with formulation components such as sucrose during concentration and buffer exchange. The MIR signal enabled robust identification of buffer-exchange endpoints independent of the exact buffer recipe. For continuous diafiltration, installing sensors in both retentate and permeate lines provided complementary information on protein and excipient transport; inline results matched offline references with typically <5% relative deviation. Overall, MIR-based PAT with Monipa reduces analytical latency and enables accelerated, information-rich UF/DF development and scale-up.

[1] Claßen J et al. Anal Bioanal Chem. 2017;409:651-666. doi:10.1007/s00216-016-0068-x
[2] Marienberg H et al. Eng Life Sci. 2024;24:e2300237. doi:10.1002/elsc.202300237
[3] Milewska A et al. Eng Life Sci. 2023;23:e2200050. doi:10.1002/elsc.202200050