Industry use of sensing technologies was previously limited to monitoring bioreactor conditions. Today, next generation tracking systems are helping drug firms optimize product quality and, says the author of a new study, cut costs.

The research—by scientists at Polytechnique Montreal, the Human Health Therapeutics Research Center, and the University of Montreal—looked at how industry approaches to process monitoring are evolving in the digital age.

And the changes are dramatic, according to lead author Juan Sebastian Reyes, department of chemical engineering at Polytechnique Montreal, who says the resolution has sharpened from inside the bioreactor to inside the cell.

“Standard probes like pH and dissolved oxygen are used to know the real time value and act on the knowledge to keep that value within a set range. But now, we see more novel technologies that give information that is more deeply connected to the direct metabolic activity of the cells,” he explains. “If data can then be linked to our biological knowledge of the cell, then those probes are helpful in helping researchers develop smarter control of nutrient concentrations.”

Reyes cites monitoring techs that track inter-cellular metabolic activity as an example, noting that “these can tell us about cellular growth or protein production patterns.”


Bio capacitance monitoring, also known as dielectric spectroscopy, is a technique used to measure biomass in cell culture processes in real-time. The idea is to use the resulting data to automate culture control steps such as on-demand nutrient feeding.

Industry use of this approach has increased in recent years partly due to the availability of new more cost-effective monitoring technologies.

“Bio capacitance probes have greatly reduced in cost over the years and have become more widespread in their application for real time monitoring of total cellular biomass in the reactor. This in turn has allowed some companies to develop feeding strategies based on the capacitance signal that has turned out to be scalable across scales,” he tells GEN.

He also points to dissolved carbon dioxide probes and Raman spectroscopy as examples of monitoring technologies and methods that are gaining in popularity.

“Dissolved carbon dioxide probes have also become useful tools when it comes to problem solving process issues at large-scale reactors given that it can be determined right away if the suboptimal process outcomes at the large scale are due to insufficient carbon dioxide striping,” he continues. “Raman spectroscopy remains new and not widely used. But once the technology matures and modeling strategies of the data also mature the ability to know in real time concentrations of nutrients will open new frontiers to better optimize the internal conditions of the reactors without frequent sampling.”

And as biopharma embraces the “industry 4.0” model of data gathering and modeling, monitoring technologies are likely to become even more important, according to Reyes.

“4.0 will force a lot of teams to look into multivariate data analysis to carry out exploratory analysis of such high-dimensional data,” he predicts. “Many teams will also try to relate the data from these new technologies to process controls in order to make better informed decisions about what type of aeration strategies and mixing strategies to use in a bioreactor for a given cell line.”

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