Sensor systems for bioprocess monitoring

Abstract

The ability to measure all process variables is of great importance in the field of bioprocess monitoring and control, and continuous, real‐time measurements are highly desired. The more complete and real‐time the measurements are, the more stable, reproducible, and efficient the process can be, leading to reproducibly high‐quality products. This additional information allows the operator to better document the entire process. The process analytical technologies initiative of the US Food and Drug Administration is strongly related to the analysis and control of biopharmaceutical processes. The aim of the initiative is to create processes, generating products of ensured quality by measuring quality‐related process variables. The quality of the product is enhanced by a deep understanding of the process, which is enabled by an effective and suitable sensor system. The aim of this review is to provide an overview of current and emerging sensors for bioprocess monitoring. Sensors directly interfaced to bioreactors for measuring important variables from the gas phase, such as oxygen and carbon dioxide concentration, are discussed, as well as sensors for the monitoring of the biomass concentration and morphology and of the changing medium composition. Furthermore, sensor systems are discussed. These involve sensors (especially biosensors) that are not implemented directly inside the bioreactor but rather are used in conjunction with sample‐taking systems such as flow injection analysis. A major focus is given to spectroscopic sensors, which are noninvasive and offer interesting options for a simultaneous analysis of various compounds. Since data handling is extremely important for this kind of sensor, chemometrics are also included. Soft sensors are discussed as technology that allows a user to incorporate more process data as it become available. Finally, the current state of disposable sensor technology is presented. These sensors are needed for the growing area of disposable and continuous biomanufacturing.

Environmental Control in Flow Bioreactors

“…The importance of chemical and physical measurements is reported in [6], where the authors also outlined the difference between on-line, in-line, and at-line measurements. In particular, on-line data are defined as signals that are available continuously, while sequential data can be defined as quasi-on-line measurements.…”

A brief review on biotechnological process sensoring

“…In [21], the authors present several utilizations of electrochemical sensors for monitor relevant variables for bioprocess. From those, the utilization of Ion-sensitive field effect transistors (ISFETs) are presented as a remarkable alternative to common glass type devices.…”

Dynamic mass spectrometry probe for electrospray ionization mass spectrometry monitoring of bioreactors for therapeutic cell manufacturing

“…Current methods for continuous monitoring of therapeutic cell cultures, such as pH measurement, temperature measurement, off-gas mass spectrometry (i.e., MS monitoring of volatile compounds produced by cells in culture via mass spectrometry), infrared and near-infrared spectroscopy, and Raman spectroscopy noninvasively capture bulk characteristics, but are subpar in offering detailed information such as the secretome’s complete biochemical composition or spatial heterogeneity within the bioreactor (Abu-Absi et al, 2011; Biechele, Busse, Solle, Scheper, & Reardon, 2015; Forcinio, 2003; Zhao, Fu, Zhou, & Hu, 2015). Some progress has been made in the implementation of noninvasive technologies that deliver multidimensional information about the cell population in a bioreactor.…”