Multipoint Analysis in Biological Production by Process Mass Spectrometry

In recent years, the utilization of online process analytical technology (PAT) has become a high-profile endeavor in the biotechnology industry.

Since the early 1980s, a number of fermentation scientists have employed Thermo Scientific™ Process Mass Spectrometers to reliably monitor the composition of gas streams into and out of bioreactors and fermenters.

When making the first steps towards process control, it is not uncommon for some to think that the measurement of carbon dioxide and oxygen in the effluent is all that is needed and that sufficient accuracy can be acquired by discrete measurement technology. Both of these assumptions are incorrect.

Due to external biology (trees and people) that inevitably alter the input to the instrument air system, the sparge gas is always variable. The ubiquitous twin-tower desiccant dryer systems will also either regurgitate or absorb CO2 depending on their place in the regeneration cycle.

In order to supply accurate pre-screening for possible contamination, only an accurate comparison of effluent and sparge gas is sufficient. To calculate real-time information regarding culture respiration and the availability of nutrients, an accurate comparison is also needed.

For effective control, the minimum requirements are as follows:

  • Measurement of sparge and effluent gases
  • Local support
  • Flexible analysis schedules and techniques
  • All gas components must be measured
  • Operational reliability and simplicity
  • High accuracy is needed to calculate meaningful metrics
  • Automatic calibration of all components 

Typical benchtop bioreactor.

Figure 1. Typical benchtop bioreactor. Image Credit: Thermo Fisher Scientific – Environmental and Process Monitoring Instruments

Source: Thermo Fisher Scientific – Environmental and Process Monitoring Instruments

Magnetic Sector
Analytical Performance
N2 N2 O2 O2 Ar Ar C2 C2
%mol %mol %mol %mol %mol %mol ppm ppm
Mean St Dev Mean St Dev Mean St Dev Mean St Dev
Day 1 78.0807 0.0028 20.9459 0.0026 0.9337 0.0003 396.84 1.31
Day 2 78.0767 0.0023 20.9494 0.0023 0.9342 0.0003 397.46 1.25
Day 3 78.0761 0.0024 20.9500 0.0023 0.9342 0.0003 397.34 1.28
Day 4 78.0798 0.0023 20.9469 0.0023 0.9337 0.0003 396.31 1.31
Day 5 78.0777 0.0030 20.9487 0.0028 0.9339 0.0003 396.76 1.34
Day 6 78.0741 0.0023 20.9518 0.0022 0.9344 0.0003 397.47 1.27
Day 7 78.0750 0.0023 20.9512 0.0022 0.9342 0.0003 397.23 1.30

 

Taking the First Steps Towards Advanced Process Control

A fully instrumented fermentor is shown in the process diagram. In order to monitor a large variety of process variables in real-time, both liquid and gas-phase measurements are supplied. 

These data are fed into the advanced process control (APC) system, which usually includes hybrid models made up of neural (nonlinear) network models and formal (linear) models. 

The APC system supplies the set-points for many variables, which include control of nutrients, sparge content and flow, amino acids, in addition to the traditional variables of temperature, agitation, pressure, and pH. 

This diagram represents the ideal situation for process understanding and scale-up, but there is an amount of complexity and cost associated with this comprehensive technique. 

As it supplies significant added value with minimum risk and moderate cost, the more common technique is to add a multistream mass spectrometer. Without compromising sterility, the Thermo Scientific™ Prima PRO is equipped to monitor 60+ fermentors. 

The Prima BT supplies a bench-top solution for smaller-scale fermentors that are configured with 15 samples and six calibration ports. The complete, highly precise gas composition measurements supplied by both models are incorporated easily into the APC system. 

Huge enhancements in process control can be attained extremely quickly, normally within one or two days of a startup. 

Fully instrumented fermentor.

Figure 2. Fully instrumented fermentor. Image Credit: Thermo Fisher Scientific – Environmental and Process Monitoring Instruments

Supplying Value During Every Stage of Product Development

Advanced instrumentation is required for the complex manufacturing processes which are inherent in biotechnology in order to ensure an optimal path to the final product. The key to increasing profits is mitigating risk throughout the scale-up process. 

The Prima PRO and Prima BT process mass spectrometers provide the precision and speed needed to track process dynamics reliably and enable timely corrective action to be taken. 

The Prima platform technology helps bring products to market more quickly, enhance profits and increase yields, and for a rapid return on investment, from research and development to the final product creation. 

Acknowledgments

Produced from materials originally authored by Thermo Fisher  Scientific

This information has been sourced, reviewed and adapted from materials provided by Thermo Fisher Scientific – Environmental and Process Monitoring Instruments.

For more information on this source, please visit Thermo Fisher Scientific – Environmental and Process Monitoring Instruments.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Thermo Fisher Scientific – Environmental and Process Monitoring Instruments. (2021, February 19). Multipoint Analysis in Biological Production by Process Mass Spectrometry. AZoM. Retrieved on May 08, 2021 from https://www.azom.com/article.aspx?ArticleID=20089.

  • MLA

    Thermo Fisher Scientific – Environmental and Process Monitoring Instruments. "Multipoint Analysis in Biological Production by Process Mass Spectrometry". AZoM. 08 May 2021. <https://www.azom.com/article.aspx?ArticleID=20089>.

  • Chicago

    Thermo Fisher Scientific – Environmental and Process Monitoring Instruments. "Multipoint Analysis in Biological Production by Process Mass Spectrometry". AZoM. https://www.azom.com/article.aspx?ArticleID=20089. (accessed May 08, 2021).

  • Harvard

    Thermo Fisher Scientific – Environmental and Process Monitoring Instruments. 2021. Multipoint Analysis in Biological Production by Process Mass Spectrometry. AZoM, viewed 08 May 2021, https://www.azom.com/article.aspx?ArticleID=20089.

Tell Us What You Think

Do you have a review, update or anything you would like to add to this article?

Leave your feedback
Submit