Using smart sensors to optimize bioreactor yields

Smart sensors enable precise condition control in bioreactors, opening up new opportunities in healthcare and the pharmaceutical industry.

Using smart sensors to optimize bioreactor yields

Image Credit: Sensirion Inc

By incorporating connected systems, manufacturers of pharmaceutical instruments can offer improved yields at affordable costs, along with valuable additional functionalities.

Bioreactors play a crucial role in cultivating various organisms, such as enzymes, plant and animal cells, and microorganisms. These active ingredients are vital for medical drug research, treatment development, clinical trials, and the production of high-value pharmaceuticals.

Monoclonal antibodies used in the treatment of cancer, rheumatoid arthritis, and other diseases, as well as mRNA vaccines, are produced in these vessels. Additionally, life science pioneers anticipate the future ability to cultivate organs and muscle tissue.

Whether in pharmaceutical R&D, large-scale manufacturing, or medical treatment, bioreactors must provide an optimal environment for sensitive microorganisms to interact, grow, and adapt to the environmental conditions of the apparatus.  

For ideal cell growth in terms of quality and output, the environment of biotic populations needs to be precisely controlled. This entails meticulous regulation of pH value, temperature, air, and gas supply (such as nitrogen), as well as nutrient availability.

While the concept of environmental control is not new, the increasing demands of today's organic material cultivation make it necessary to carefully synchronize the physiochemical dependencies of each parameter.

The expanding range of bioreactor applications and the desire to minimize contamination risks for operators while avoiding disruptions in ongoing processes complicate matters further, making conventional "measuring by sampling" less viable.

Image Credit: Shutterstock.com/FOTOGRIN

Versatility, repeatability, and efficiency

Bioreactors must be able to accommodate diverse cell types. Take, for instance, the production processes of the influenza vaccine, which vary annually due to the emergence of different viruses with slight variations during each cold season.

As shown by the recent pandemic, there was an urgent need for large quantities of cultivated cells within short timeframes, resulting in high demand for maximum yields. Generating substantial quantities of mRNA vaccines necessitated highly efficient reactors and a high level of process reliability and repeatability.

These requirements extend to all applications of bioreactors used in manufacturing high-volume drugs.

With the advancement of biotechnology and recent experiences, pharmaceutical manufacturing and healthcare demands also call for increased robustness to enhance yields.

Meeting these new requirements entails developing innovative bioreactor designs and implementing new process control concepts utilizing smart sensors that are biocompatible, fast, stable, accurate, and easy to clean (unless they are disposable).

Parameters for optimum cell growth

To create favorable physiochemical conditions and enable swift adjustments for specific cell cultures, it is necessary to measure the following parameters within a bioreactor:

  • pH-value 
  • Temperature 
  • Humidity 
  • Gas and liquid concentration 
  • Gas and liquid flow 
  • Headspace pressure

In most instances, the temperature is maintained at 37 °C, and the CO2 concentration is kept at 5% throughout cell growth. However, there are situations where these parameters need precise adjustment to achieve the desired pH range, which takes precedence.

Frequently, the pH value must be controlled within the narrow range of 7.0 to 7.4. Maintaining stability within this limited range can pose challenges, considering the need for a simultaneous balance of various other parameters, including temperature, cell growth, lactic acid, and CO2 levels.  

To achieve this, buffers are utilized to neutralize any additional acid (H+ ions) or base (OH ions) and maintain a stable pH value.

Precise control of oxygen concentration is crucial. For most cell cultures, it is necessary to maintain it at 20%, although some cultures may thrive better under different conditions.  

Therefore, efficient transfer of oxygen from the gaseous to the liquid state in the cell culture medium is vital to ensure optimal cell metabolism. The efficiency of oxygen transfer is influenced by factors such as temperature, pH value, and gassing rate.

Lastly, it is essential to maintain stable humidity levels and continuously monitor them to identify any failures in the evaporation system.

The same applies to the headspace pressure, particularly in single-use bioreactors, as their flexible 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 maintaining control over conditions, connected sensors play a pivotal role in bioreactors. Employing multiple intelligent sensor systems enables highly precise control of physiochemical processes and accurate monitoring, thereby elevating the performance of the apparatus to new heights.

Achieving successful cell growth can be a complex task due to the interdependencies among various parameters. To optimize the growth of organic materials cost-effectively, the easiest approach is to consistently monitor and control the cultivation conditions using a closed-loop system.

Ensuring stable environments is particularly crucial for the production of high-volume drugs and during the drug design research and development (R&D) phase. Even slight deviations occurring for a brief period can impact the desired output of organic material.

Cutting-edge sensors that facilitate real-time feedback loops not only enable bioreactors to promptly and precisely adjust conditions but also detect any failures.   

In the event of deviating set points, an automated system triggers an alarm and safeguards the vat, preventing potential damages and the wastage of expensive materials (such as in the case of overpressure in single-use devices).

Accordingly, different types of sensors may be utilized to detect various failure modes. For instance, liquid concentration sensors can also be deployed to verify the injection of the correct liquid into the device.  

Likewise, liquid flow sensors can be employed to measure total dispensed volumes (especially for costly liquids) and accurately dose multiple liquids to achieve the desired concentration.

The same principle applies to gas flow sensors. In essence, feedback loops contribute to safe and reliable process optimization.

In certain bioreactors, the implementation of multiple sensors of the same type can prove beneficial. For example, having one sensor at the inlet and another at the outlet of the bioreactor helps in obtaining spatial information from different locations, leading to a better understanding of the physiochemical processes in the cell culture.

An additional advantage of a smart control system is its ability to log sensor data and store it in a database. Should the growth results prove unsatisfactory, having an easily accessible logbook containing all measured parameters provides clarification.

Particularly for safety and research purposes, having access to the data history of a cultivation process can be extremely valuable. By utilizing a tracking system, operators can swiftly identify the root causes of failures and make necessary process modifications. 

Image Credit: Sensirion Inc

The solution: Reliable, fast, and robust sensors

Recent advancements in MEMS-based sensors have resulted in the development of compact, high-performance solutions that consume low power.

These sensors are well-suited for single-use bioreactors, which require smaller quantities of water and detergents compared to traditional bioreactors, eliminating the need for cleaning or maintenance procedures.

In addition to the environmental benefits, these applications offer cost reductions and improved turnover rates.  

Sensirion provides an extensive range of high-performance sensors, including single-use sensors, designed for precise process control and accurate monitoring in various bioreactor types, from pilot to commercial manufacturing.

By integrating Sensirion's biocompatible sensors into existing bioreactors, users can easily upgrade their equipment instead of purchasing new ones.  

These digital sensors, manufactured in Switzerland, cover wide measurement ranges while maintaining high accuracy, even at the lowest limits. Consequently, they have become highly sought-after components for advanced bioreactors across multiple pharmaceutical sectors.

About Sensirion Inc

Sensirion

Medical devices must meet the highest standards in terms of quality and reliability. Doctors, nurses, and patients benefit daily from applications in the field of medical technology that are getting smarter by the day.

The use of proven Sensirion sensor solutions contributes to this and offers the possibility of making applications safer, more reliable and more convenient. Our many years of experience in the field of medical technology make us the preferred experts for leading medical-technology companies.

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Last updated: Jun 22, 2023 at 10:30 AM

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