In upstream bioprocessing, especially perfusion, one of the biggest challenges is maintaining tight control of viable cell density (VCD) in real time. Manual sampling methods like those involving Trypan Blue, a staining assay where dead cells absorb the dye and turn blue, while live cells exclude it, are off-line, time-delayed and prone to variability. That’s far from ideal for continuous processes.

A Modern Approach: Capacitance Sensing + SA-PLS Modelling

A recent study by WuXi Biologics evaluated ABER Instruments’ Futura multi-frequency capacitance probe combined with a segmented adaptive PLS (SA-PLS) model, achieving automated VCD control with significant improvements in both accuracy and robustness.

Key Performance Improvements

Compared to traditional approaches, the SA-PLS model delivered:

• RMSE down to 1.35 × 10⁶ cells/mL during stationary/decline phases
• Up to 55% reduction in VCD fluctuation versus manual control
• Real-time feedback for automated bleeding, with updates every minute

Intelligent Adaptation Across Growth Phases

What makes this particularly interesting is its ability to account for complex changes in cell physiology over time. By switching between tailored models for different growth phases, SA-PLS maintains accurate predictions, even as cell morphology evolves.

From Passive Monitoring to Active Control

This shifts ABER’s dielectric spectroscopy technology from a passive monitoring tool to an active control strategy, supporting more consistent, scalable, and efficient perfusion processes. The ability to maintain target VCD with minimal manual input reduces variability and helps operators respond rapidly to process shifts, crucial for modern biologics manufacturing.

Enabling Smarter, More Stable Bioprocessing

By combining ABER’s proven multi-frequency capacitance sensing with a robust modelling approach, the system enhances the distinction between viable and non-viable biomass. This enables more accurate bleeding decisions and improved culture stability without disrupting existing workflows or requiring excessive recalibration.

A Core PAT Solution for Continuous Manufacturing

For manufacturers progressing toward intensified or continuous operations, this study highlights a compelling case for adopting ABER’s Futura platform as a core PAT solution, moving beyond monitoring toward model-driven, closed-loop control.