Microfluidic solutions for process and quality control in life science applications

Article | Bartels Mikrotechnik GmbH

When culturing cells, it is essential to observe carbon dioxide and solved oxygen levels, pH values and optical densities. Additionally, when ambient pollution has to be measured, volatile organic compound (VOC) sensors are used.

Sensing ambient gas phase compositions is a crucial task in today’s biotech life as it is a contamination-free principle. Be it for containing stable conditions or for supervising potential toxic concentrations, in many circumstances gas phase analysis has become a powerful tool.

Case Study: In-situ cell culture monitoring
Due to the request for higher safety and efficiency in industrial processes, the use of sensors increases continuously. Since various sensors can not be used with completely passive feeding, the mp6 micropump from Bartels Mikrotechnik GmbH opens up new fields of application. Due to their simple setup, they can be produced at a low cost level. Additionally, thanks to their particle tolerance, they prove efficient under ambient conditions.

With its small dimensions, the mp6 micropump can either be used as a subassembly together with the sensor or as an OEM (original equipment manufacturer) component to be integrated into a more complex unit. Especially for portable instruments, where miniaturization plays an important role, the low energy consumption comes into play. Battery operation may be easily realized. Depending on the customers needs, the driving electronics are either integrated into the main PCB (printed circuit board) of the unit or even inside an enlarged pump housing.

The use of an inert polymer in combination with an optimized placement of the pump inside the system enables operation under the most demanding conditions.

The micropump mp6 provides a minimum flow rate of 6 ml/min for liquids (with dynamic viscosities of  and 18 ml/min for gases. By using the available evaluation kit, the pump performance can be tested in the target application and the driving parameters can be defined.

For once the CO2 concentration gives information about the grown cellcultures. The higher the emitted amopunt of CO2 the higher the number of individual cell already developed.

To verify whether differences in gas concentrations can be detected after passing through the mp6 micropumps, a reservoir including a sealed lid with four ports is utilized.

One port is connected to a pressure sensor by Honeywell to monitor the pressure inside the reservoir. Additionally, two valves which are connected antiparallel to each other can regulate pressure differences within a margin of their opening pressure (40 mbar).

For the Sensor setup, two ports are reserved in order to transport produced gases via a closed-loop. The VOC-Sensor SGP40 by Sensirion is connected to a breadboard while the electrical supply for the CO2-Sensor SCD40, which is also manufactured by Sensirion, is assured by the mp-Multiboard2 by Bartels Mikrotechnik GmbH. To prevent fresh oxgen flowing into the reservoir, active valves are implemented that also ensure clean tubes.

If needed, a fourth port for fluid transportation into or out of the reservoir is available.

Functional CO2- and VOC-sensing has been observed. By filling the reservoir with yeast and a nutrient medium the fermentation of beer has been observed and could be verified by sensor results.

It shall be noted that high VOC-concentrations correspond to low count rates by the SGP40 sensor because the sensor is observing the degree of air quality, hence the inverse of pollution levels. Moreover, the CO2 concentration is directly given in ppm while the VOC-sensor only provides count rates, whose quantitative concentrations were not calculated yet. The most probable main component accountable for VOC-counts is ethanol (C2H5OH).

It is logical that by letting the mixture ferment more cells are produced. Thus the carbon dioxide concentration rises with developed fermentation processes to a point beyond the sensors sensing limits.

Furthermore, by observing the amount of VOC counts it is possible to determine the ethanol content within the reservoir. Via mentioned setup, the dilution of beer is traced. As can be seen, the lower the ethanol concentration the higher the detected VOC counts. Following these findings, the ethanol concentration is obtained and monitored through gas phase analysis without any contamination.

In conclusion, CO2 as well as VOC concentrations rise with advanced fermentation. That way, by simply assigning a reference (e.g. beer with 4.8% C2H5OH), the fermentation process of yeast into beer can be protocolled industrially with very little space and resources needed. Since all data can be obtained via gas phase analysis, contaminants are mostly excluded from the measurement.

About the company
Bartels Mikrotechnik is a globally active manufacturer and development service provider in the field of microfluidics. In the microEngineering division, the company supports industrial customers in the modification, adaptation and new development of high-performance and market-oriented product solutions through the innovative means of microsystems technology. The second division, microComponents, produces and distributes microfluidic products and systems, especially for miniaturized and portable applications. Our key products are micropumps that convey smallest quantities of gases or liquids and are used in a variety of ways in biotechnology, pharmaceuticals, medical technology and numerous other applications.

Bartels Mikrotechnik with passion for microfluidics!
www.bartels-mikrotechnik.de

Author

Florian Siemenroth
Product Manager
Bartels Mikrotechnik GmbH