Portable Analytical Techniques for Monitoring Volatile Organic Chemicals in Biomanufacturing Processes: Recent Advances and Limitations

Abstract

It is essential to develop effective analytical techniques for accurate and continuous monitoring of various biomanufacturing processes, such as the production of monoclonal antibodies and vaccines, through sensitive and quantitative detection of characteristic aqueous or gaseous metabolites and other analytes in the cell culture media. A comprehensive summary toward the use of mainstream techniques for bioprocess monitoring is critically reviewed here, which illustrates the instrumental and procedural advances and limitations of several major analytical tools in biomanufacturing applications. Despite those drawbacks present in modern detection systems such as mass spectrometry, gas chromatography or chemical/biological sensors, a considerable number of useful solutions and inspirations such as electronic or optoelectronic noses can be offered to greatly overcome the restrictions and facilitate the development of advanced analytical techniques that can target a more diverse range of key nutritious components, products or potential contaminants in different biomanufacturing processes.

Keywords: analytical methods; biomanufacturing; bioprocess assessments; electronic noses; sensors; volatile organic chemicals.

Figure 1

Illustration schemes of the set-ups for biomanufacturing monitoring. (A) Scheme of in-line vs. off-line analysis of bioreactors. (B) Scheme of the mechanism and interpretation of a typical electronic nose (E-nose) system made of optically responsive sensors. (C) Headspace VOC analysis of a growing cell culture in a bioreactor using ambient mass spectrometry. Reproduced with permission from Chingin et al. (2014). Copyright Royal Society of Chemistry 2014. (D) Illustration of electronic noses and pattern recognition.