TY - JOUR

T1 - Sensor systems for bioprocess monitoring

AU - Biechele, Philipp

AU - Busse, Christoph

AU - Solle, Dörte

AU - Scheper, Thomas

AU - Reardon, Kenneth

PY - 2015/4/8

Y1 - 2015/4/8

N2 - 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.

AB - 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.

KW - Bioprocess monitoring

KW - Cell culture

KW - Process analytical technology

KW - Process control

KW - Sensor systems

UR - http://www.scopus.com/inward/record.url?scp=84935722636&partnerID=8YFLogxK

U2 - 10.1002/elsc.201500014

DO - 10.1002/elsc.201500014

M3 - Article

AN - SCOPUS:84935722636

VL - 15

SP - 469

EP - 488

JO - Engineering in life sciences

JF - Engineering in life sciences

SN - 1618-0240

IS - 5

ER -