Scaling Up with Confidence: Harnessing Bio-Capacitance as a Scalable PAT Tool
Transferring an upstream cell culture process between different bioreactor volumes is one of the most critical and challenging phases of biopharmaceutical production. Whether scaling up from development to commercial manufacturing or scaling down to troubleshoot critical process parameters (CPPs), maintaining consistency is vital. Delays or unexpected shifts in key process indicators (KPIs) can cost hundreds of thousands of pounds in wasted media and resources per re-run, alongside substantial opportunity costs in delayed clinical trials. To achieve successful technology transfer without data gaps, bioprocess scientists require scalable Process Analytical Technology (PAT) that delivers a continuous, scale-independent signal. This article highlights how ABER Instruments' capacitance-based sensors serve as an essential tool for seamless process scaling from high-throughput mimics through to commercial cGMP manufacturing.
Key Takeaways: Multi-Scale Biomass Monitoring with Futura
- The Power of Bio-Capacitance: ABER’s Futura technology utilises dielectric spectroscopy to measure the charge retained by cells with intact membranes. This approach isolates live cells from dead cells and debris, providing precise, real-time measurements of viable cell concentration (VCC) and biomass.
- Scale-Independent Principles: All sensors in the ABER Futura range share the same measurement principle and signal processing algorithm, providing high process comparability across vessel geometries and sampling volumes using picofarads per centimetre (pF/cm).
- Versatile Hardware Integration: The technology spans the entire development pipeline, integrating with small-scale bioreactor mimics (such as the Ambr
250 high-throughput system), benchtop glass vessels, single-use rocking motion (RM) systems, and stainless-steel stirred tank reactors (STRs) up to 20,000 L.
- Proven Transferability: Published studies demonstrate a strong linear correlation (R^2 = 0.99 during exponential growth) between in-line capacitance and offline VCC across scales ranging from 5 L benchtop systems up to 2,000 L and 15,000 L commercial vessels.
- Robust Data Communication: A wide range of communication protocols - including USB, analogue, and digital options - allows data to be exported to different controllers and endpoints for streamlined system integration.
Why Real-Time Capacitance Matters to Your Bioprocess
Traditional offline or at-line analytical methods, such as trypan blue exclusion, rely on manual sampling at 12- to 24-hour intervals. This approach creates distinct data gaps, consumes valuable working volume, and introduces a risk of contamination to the bioreactor.
In contrast, in-line bio-capacitance provides a continuous, non-invasive "fingerprint" of the culture by taking readings every few seconds. For our customers, this constant stream of real-time data means process deviations can be detected and corrected as they happen, safeguarding expensive production batches.
Furthermore, because ABER’s reusable and single-use Futura sensors show minimal variance (within 2%) and no significant drift when run alongside each other, you can transfer processes between single-use and reusable hardware platforms with minimal need for recalibration or revalidation.
Insight: Automating Control via the "Golden Batch"
By capturing a high-resolution profile of an ideal run, bioprocess engineers can establish a "golden batch" capacitance trend. This trend can then be utilised during scale-up to trigger automated feedback loops.
Instead of waiting for manual sample data, the real-time capacitance signal can automatically control nutrient feed strategies or precisely identify optimal inoculation windows. This real-time automation reduces human error, optimises cellular performance, and accelerates technology transfer timelines from bench to bedside.
Explore the complete ABER Instruments range or speak to our team today to discover how we can support your bioprocess scaling strategies.