Laboratory Products
Optimising Bioreactor Yields with Smart Sensors Gina Greco, Sensirion AG
Smart sensors for accurate condition control in bioreactors create new opportunities in healthcare and the pharmaceutical industry. By integrating connected systems, pharmaceutical instruments manufacturers can offer higher yields at reasonable cost as well as key additional features.
Bioreactors are used, among other things, to grow organisms such as enzymes, plant and animal cells, and microorganisms. Such active ingredients are used for medical drug research, treatment development, clinical trials and the production of high-value pharmaceuticals. Besides the latest example of mRNA vaccines, monoclonal antibodies for treating cancer, rheumatoid arthritis and other diseases are produced in these vessels. Life science innovators assume they will likely be able to grow organ and other muscle tissue in the future.
Whether in pharmaceutical R&D, large-scale manufacturing or medical treatment, bioreactors must provide a perfect environment under which sensitive microorganisms can change and grow by interacting with one another and under the infl uence of the apparatus’ environmental conditions. For ideal cell growth in terms of quality and output, the environment of biotic populations needs to be controlled precisely. Fundamentally, that means maintaining pH value and temperature, ensuring the supply of air, nitrogen and other gases as well as nutrients.
This is not new, but today’s increased requirements can make the growing of organic materials so complex that the physiochemical dependencies of the individual parameters have to be carefully synchronised with each other. In addition, the more and more versatile deployment of bioreactors, the aim to reduce contamination risks for operators and avoid disrupting ongoing processes by conventional “measuring by sampling” are complicating the matter, too.
Versatility, repeatability and effi ciency
Bioreactors must be able to accommodate different cell types. If we take a look at the infl uenza vaccine, for example, its production processes vary from year to year, as different viruses with slightly different characteristics develop in each cold season. Moreover, as the pandemic has shown us, large quantities of cultivated cells were needed from one day to the next, resulting in a high demand of maximum yields. Producing huge amounts of mRNA vaccines not only required reactors with high effi ciency, but also a high process reliability and repeatability. These requirements also apply to any other application of bioreactors, which are deployed for all kinds of high-volume drug manufacturing.
With the rise of biotechnology and recent experiences, pharmaceutical manufacturing and healthcare needs also require a higher robustness in order to increase yields. The key to meeting the new needs lies not only in the development of novel bioreactor designs, but also in new process control concepts using smart sensors that are biocompatible, fast, stable, accurate and easy to clean (if they are not disposable).
Parameters for optimum cell growth
Creating physiochemical conditions and enabling fast adjustments for specifi c cell cultures require the measurement of the following parameters inside a bioreactor:
• pH-value • Temperature • Humidity
• Gas and liquid concentration • Gas and liquid fl ow • Headspace pressure
In most cases the temperature is kept at 37°C and the CO2 concentration at 5% during cell growth. However, in some cases these parameters must be fi nely adjusted to reach the target pH range, to which priority is given.
Often, the pH value must be kept in between 7.0 and 7.4. Keeping it stable in this narrow range can be challenging, insofar as there are several other parameters that have to be balanced in parallel, such as temperature, cell growth, lactic acid and the CO2 level. This can be done by so-called buffers, which neutralise any additional acid (H+ ions) or base (OH ions) to keep the pH value stable.
Furthermore, the oxygen concentration requires precise control. For most cell cultures it must be kept at 20%; occasionally, some cultures grow better under different conditions. Therefore, it is fundamental that the oxygen effi ciently transfers from the gaseous to the liquid state in the cell culture medium so that the cell metabolism functions as quickly as possible. The effi ciency of the oxygen transfer is affected by the temperature, the pH value and the gassing rate.
Finally, humidity should be stable and monitored in real-time to detect evaporation system failures. The same applies for the headspace pressure, particularly in single-use bioreactors since their fl exible plastic bags cannot withstand overpressure of a few hundred millibars over a long period of time.
Condition monitoring, failure detection and data logging
When it comes to keeping conditions under control, connected sensors play a key role in bioreactors. Multiple smart sensor systems for highly precise physiochemical process control and accurate monitoring can take the performance of such an apparatus to the next level.
INTERNATIONAL LABMATE - JULY 2022
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