In-process monitoring of an Industrial Fermentation process

Industrial Fermentation Vat - Keit IRmadillo

In situ process analytical technology (PAT) of chemical and biochemical reactions is one of the most powerful tools in modern science. Spectroscopy-based PAT represents a very real route to saving money by allowing real-time prediction of concentrations of key chemicals and species within fermentations.

Importantly, monitoring the concentrations of sugars during a process allows very fine control of dosing levels and rates. For example, maintaining a constant level of glucose may allow fine control of the rate of fermentation and prevent thermal runaway. Alternatively, in situ PAT allows the detection of key failure markers (such as lactic acid) much earlier than extractive sampling techniques (such as HPLC). This enables the operator to immediately catch problems and potentially save batches that may have otherwise been lost.

All spectroscopic PAT techniques are incredibly powerful — such as Raman, FTIR and NIR — as they directly monitor different species simultaneously, and can cope with a range of concentrations. However, conventional spectroscopic techniques can suffer from fragility (in the case of standard FTIR instruments), or low sensitivity and specificity (in the case of NIR instruments), or even poor repeatability and performance drift (in the case of Raman) — making the use of them in industrial settings challenging.

Here we present the use of an innovative, robust and vibration-resistant FTIR spectrometer – the IRmadillo — to monitor different fermentation processes. The spectrometer has successfully monitored ethanolic fermentation of sucrose as well as commercial industrial fermentations.

IRmadillo &  Fermentation Analysis

The IRmadillo was used to monitor two different fermentation processes over 50 hours – a classical sucrose-yeast fermentation and an industrial bacterial fermentation. The IRmadillo was either incorporated directly into a fermentation vessel through a side port, or placed in-line into a multi-stage process using a flow cell and peristaltic pumps. The production of six different chemical species was simultaneously monitored in real time with concentrations ranging from 0.1 to 25 g L-1 using chemometric methodology.

Keit fermentation monitoring - IRmadillo
Figure 1: Plot of chemicals monitored by IRmadillo during fermentation over 50 hr process

The spectra were also analysed using classical methods to highlight any build-up of biofouling in the system. The IRmadillo can be used to directly improve processes by indicating when the system requires a filter change.

Keit IRmadillo feedstock & biofouling
Figure 2: Contour plot of all spectra acquired during process along with trend analysis


These results show that the IRmadillo can be effectively used to monitor different types of fermentations. Both yeast- and bacterial-based fermentations can easily be monitored, with the probe inserted either directly into the fermentation vessel or in-line via a flow cell.

In operando use of the IRmadillo allows the concentration monitoring of multiple different chemical species simultaneously, with six different components being demonstrated here, over several orders of magnitude in concentration ranges.

Furthermore, it is possible to classically analyse the spectra to gain information about the process and to improve understanding. This can lead to direct process improvements such as process-led filter changes.

This work shows that the application of PAT through the introduction of the IRmadillo into industrial fermentations can help to reduce waste and improve efficiency, ultimately cutting costs.

Industrial Applications

Fermentation is an integral process in many manufacturing industries such as Food & Beverage, and Bioethanol & Biofuels as well as certain processors of Pulp & Paper. Being able to accurately monitor the presence and amount of sugars and by-products in real-time is key to maintaining efficiencies — both in the production process and resource management —  inevitably affecting bottom-line costs. Keit has developed the tough IRmadillo to provide rapid insight in monitoring industrial processes including active fermentation processes.

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