Measuring Cell Density In The HyPerforma S.U.B.s With Aber Futura Neo Single-Use Sensors

Introduction
Monitoring critical process parameters (CPPs) and key performance indicators in bioreactor control systems is crucial to ensure proper cell growth and protein production. For years, the most important parameters have generally been dissolved oxygen (DO), pH, temperature, and cell concentration. Continual advancement of technology to evaluate these parameters has resulted in faster and more reliable measurements. Additionally, the move to single-use bioreactors (S.U.B.s) for bioproduction has motivated vendors to develop single-use sensors to incorporate into fully single-use workflows.

Recent advances in sensing technologies and a move toward controlling critical quality attributes of a culture have led to the development and use of more advanced sensors. Among the most highly monitored and controlled culture parameters has been cell concentration. However, to monitor cell concentration, the industry has generally relied on off-line measurement methods and analysis based on daily spot checks. The challenges to this method are well known and include contamination risks, labor-intensive work, infrequent sample points, sample variability, etc. Online measurement methods are used occasionally, mainly by development lab professionals who look to implement advanced technologies and develop higher-order control schemes.

Dielectric spectroscopy, or capacitance measurement, is a reliable and proven method of determining cell density online. This technology was invented and developed in 1988 by Aber Instruments Ltd, Aberystwyth UK. Today, most of the major biopharmaceutical companies employ capacitance measurement, in R&D and through process development to manufacturing.

Owing to the increased use of S.U.B.s and building on Aber’s experience with single-use capacitance sensors, the latest Futura™ Neo™ single-use capacitance sensors (Thermo Fisher Scientific Cat. No. SV21621.01) have been specifically developed for integration into Thermo Scientific™ BioProcess Containers (BPCs) for use in Thermo Scientific™ HyPerforma™ S.U.B.s. This application note summarizes the sensor’s function, integration into the S.U.B. BPC, and showcases functional cell culture data obtained both internally and with a primary customer.