Versatile In-Line Cytometry Probe for Continuous Process Monitoring and Analysis

Biopharmaceutical manufacturing is constrained by its reliance on offline metabolic measurements, limiting real-time control and optimization. While in-line and at-line PAT probes monitor extracellular parameters, detailed cellular-level data remain dependent on delayed offline analysis. To address this gap, Physical Sciences Inc. (PSI) developed an in-line cytometry PAT that provides real-time, continuous single-cell measurements of viable cell count, morphology, metabolic shifts, and physiological state. This technology combines light scattering and fluorescence spectroscopy of endogenous intracellular fluorophores for rapid, multi-parameter analysis. In collaboration with the University of Massachusetts Lowell, Northeastern University and Clemson University, PSI demonstrated the value of this in-line PAT instrument through real-time monitoring of FAD/NADH redox ratio in diverse bioreactor processes, including yeast metabolism, iPSC aggregates, HEK293 cultures for viral vector production, and CHO cell cultures for bioprocessing. This technology enables real-time redox data to optimize cultures, improving transfection efficiency and guiding the culture towards a desired metabolic state.