In situ sensor techniques in modern bioprocess monitoring

Abstract

New reactor concepts as multi-parallel screening systems or disposable bioreactor systems for decentralized and reproducible production increase the need for new and easy applicable sensor technologies to access data for process control. These sophisticated reactor systems require sensors to work with the lowest sampling volumes or, even better, to measure directly in situ, but in situ sensors are directly incorporated into a reactor or fermenter within the sterility barrier and have therefore to stand the sterilization procedures. Consequently, these in situ sensor technologies should enable the measurement of multi-analytes simultaneously online and in real-time at a low price for the robust sensing element. Current research therefore focuses on the implementation of noninvasive spectroscopic and optical technologies, and tries to employ them through fiber optics attached to disposable sensing connectors. Spectroscopic methods reach from ultraviolet to infrared and further comprising fluorescence and Raman spectroscopy. Also, optic techniques like microscopy are adapted for the direct use in bioreactor systems (Ulber et al. in Anal Bioanal Chem 376:342-348, 2003) as well as various electrochemical methods (Joo and Brown in Chem Rev 108:638-651, 2008). This review shows the variety of modern in situ sensing principles in bioprocess monitoring with emphasis on spectroscopic and optical techniques and the progress in the adaption to latest reactor concepts.

Optimization of Insect Cell Based Protein Production Processes - Online Monitoring, Expression Systems, Scale Up

“…This finally facilitates a fundamental understanding and allows for process control in order to reach effective processing [38]. For instance, the concentrations of key substrates and, with respect to BV infected insect cell cultures, the time of infection (TOI) and time of harvest (TOH) are well known to influence product yield [40].…”

“…Additionally, there is a growing need for bioprocess monitoring in disposable bioreactors which has been driven by the increasing demand for single use technologies in the biopharmaceutical industry [37]. Up to now, the connectivity of PAT-devices to disposable bioreactors is one of the major drawbacks [38].…”

“…Bypass configurations are particularly applied in systems where, for instance, gas bubbles in the bioreactor would interfere the measurement signal [38]. However, for bypass-measurements it needs to be considered that within the bypass changes in state of the medium e.g.…”

“…Another possibility is to utilize the sensors externally (ex situ). In this case, a sterile sample removal system forwards the medium directly to the sensor (on line) [38,42]. Since in situ sensors are placed directly in the sterile environment of the bioreactor, they have to fulfill special requirements.…”

Electrochemical detection of free chlorine at inkjet printed silver electrodes

“…electrophilic addition to styrene) [1], as well as iodometric and amperometric titrations have been employed to measure the free chlorine content in water [3]. Electrochemical methods have shown to be a good alternative for the analysis of different inorganic and organic species due to their sensitive and rapid response, in addition to their simplicity and their possible on-line operation [14]. In particular, amperometry and potential sweep techniques have been extensively involved in the direct determination of free chlorine using its electrochemical oxidation or reduction properties [15][16][17][18][19][20][21][22][23].…”