From stem cells to bacteria in food products, the applications of bioreactor systems are wide-ranging. In this interview, Bio Tech international talked to Dr. Falk Schneider, Director of Software Engineering, at DASGIP AG, about his company's unique parallel bioreactor systems that are being praised across Europe for their modular, flexible designs.
by Dr. Falk Schneider

System background and design

Q1. For those readers who are not familiar with DASGIP’s parallel bioreactor systems, can you explain how your technology works and how it can help to automate a variety of microbiological and cell culture applications?

The Parallel Bioreactor System provides comprehensive control of up to 70 process parameters for a maximum of 16 bioreactors operating simultaneously. The main process parameters that are controlled include variables such as pH, temperature and dissolved oxygen levels. The system also supports a customised substrate feed and gas supply. With working volumes starting from 35 mL for cell culture and 60 mL to 4 L for microbiology, the unique parallel system is designed for laboratory-scale applications at the R&D and product development level. As well as the parallel run of the bioreactors, parallel procedures are in place for calibration as well as cleaning (Cleaning in Place, CIP). The calibration of pH for 16 vessels or CIP for up to 64 dosing lines can be carried out in one single step. All process values measured during a process run are not only stored in a central data base for evaluation, but can also be used as online trigger signals or in freely programmable scripts. These features help to reduce the need for manual operation and optimise processes control. Users can even integrate third party lab devices such as autosamplers and analysers into the bioreactor process. The 'Control Software 4.0' and all the control modules support communication via open communication standards (OPC), seamless lab device integration and implementation of feedback control loops. This provides comprehensive lab automation, and saves time and labour costs.

Q2. How flexible is the system in order that it can be adapted to the needs of individual research projects?

Another unique characteristic of our system is its modular design. Vessels, monitoring and control functions, as well as the control software, can be freely combined to create customised bioreactor systems. In this way, particular bioreactor systems for challenging applications in microbiology, animal and plant cell cultures can be designed. This may be the reason why the company is the number one provider of controlled cultivation systems for the stem cell research community. The cornerstone may have been laid some years ago, when we developed a special miniature-scale vessel for a stem cell project. The flexibility to upgrade our systems, no matter whether in terms of number or size of operated vessels, or in terms of functionality, helps users adapt their system to the changing demands of a project in an easy and cost-efficient way.

Q3. Bioreactor systems such as these generate large amounts of process data. What type of information/data management tool does your system use?

When running up to 16 reactors and monitoring or controlling up to 70 process parameters, there are huge quantities of data that need to be managed. The  data mining tool in our systems ensures that all relevant information related to a cultivation process is collected and compiled. Data on the process preparation, strain, media and different recipe information can be manually added and stored. Raw bioprocess data can be turned into valuable process information: users can, for example, link the utilised strain or cell line and the media composition, with process conditions such as set-points and feeding profiles. Achieved product yields or viable cell densities can then be selected for to find the “Golden Batch”. The data mining 'wizard' provides an intuitive query interface that allows a set of runs to be selected and, in a single click of the mouse, generates a comparative process workbook in Microsoft Excel.

Practical applications

Q4. The parallel bioreactor systems can be used for an extremely wide variety of cell culture applications, ranging from the development of cell lines, to stem cell cultivation, and the production of recombinant proteins. Could you describe an example where an application of the bioreactor system has been put into practice in a current research project?

Scientists and process engineers around the globe are working successfully with our cell culture system. There is one exciting project that spontaneously comes to mind. It is a project of one of our industrial customers, CEVEC Pharmaceuticals in Cologne, Germany. The company is working on the production of complex recombinant proteins in a proprietary human amniocyte cell line. To enhance the protein production process, they developed a biphasic culture process based on a pH shift. The researchers evaluated the physical parameters for batch cultivation of their stable cell lines by direct comparative studies and, for different culture media, achieved optimsed metabolite consumption, cell density and viability. The biphasic culture process developed by the researchers resulted in a 6.5-fold increase in time-dependent volumetric productivity and a 14-fold increase in final product concentration.

Q5. How can the microbiological applications of the parallel reactor systems be used for the food and feed industry?

Focussing on the needs of the food and feed industries, users profit in two major ways. Firstly in R&D: most of the biotechnologically-produced food and feed additives such as antioxidants, vitamins and fatty acids have a microbial origin (just as probiotics and other lactobacilli used in dairy products do). For bacterial strain optimisation and the development of recombinant production processes, or to improve quality of dairy products such as yogurt, curdled milk or curd cheese, the parallel bioreactor systems can be of great benefit. The individual control of temperature, agitation, pH and dissolved oxygen in up to 16 parallel vessels, together with user-defined gassing, feeding and off-gas analysis, allow our fermentation systems to accommodate even the most complex microbiological requirements.

Food manufacturers can also take advatage of the modular design concept. Our customers who are mainly in dairy industries successfully use the equipment as a parallel pH monitoring tool in quality control. Since all our modules can be operated as stand-alone devices, but can also be integrated with third-party systems, they are ideal for regulating industrial production of various food products e.g. dietry supplements, diary products or beverages.

Q6. DASGIP has developed a customised parallel bioreactor system designed especially for the development and manufacture of biofuels. Could you tell us a bit more about this system?

Since biofuel development has emerged as one of the leading fields of applied sciences within the last few years, we decided to design a unique system that meets these research demands. In 2007, we launched our first parallel bioreactor system for biofuels, dedicated to the production of e.g. bio-alcohols or bio-gas. To offer gas-tight reactors for the anaerobic cultivation of microorganisms, we equipped our vessels with specific silicone or fluorine caoutchouc seals. The temperature range of the control unit and the integrated temperature and agitation regulation unit was extended from below ambient temperature to up to 100 °C. This guarantees the high temperatures required in pre-treatment of fibered raw carbon sources like cellulose, for example. Another feature we addressed was the redox control. Because a negative redox potential is essential for specific enzyme activities in anaerobic metabolism, tight control of the redox potential and pH is important. With our PHRD modules, both parameters can be measured simultaneously and then directly adjusted by systematic addition of reducing agents. Last, but not least, we have extended our line of gassing systems. Numerous input gases can now be supplied to a single bioreactor.

Now with our latest invention, the PhotoBioreactor, we also provide users working on third generation biofuels with sophisticated solutions. Phototrophic algae and plant suspensions can be cultivated under strictly controlled conditions for high biomass production. The new LED Illuminators guarantee an effective and consistent light supply. The spectral composition, as well as the light intensities, meet various requirements for photosynthesis and can be individually
controlled via software. 

Q7. Looking towards the future of microbiological and cell culture research and process development, what new developments does the company envisage that their parallel bioreactor systems will be a key part of?

We are constantly trying to develop strategies and products that make fermentation or cell cultivation work as easy as possible. In addition, the management of the huge amounts of data received from these processes is a key area of innovation and development. I think the main trends regarding these challenges are intelligent information management tools and customised solutions for the optimisation and ease of daily work flows. Big pharmaceutical companies, just as small and medium enterprises and even academia do, need to economise their budgets and resources. Focussing on lab efficiency, the data management system works using open connectivity on the one hand and remote control on the other. This not only enhances automation capabilities in the laboratory, but also helps harness the information company-wide and regardless of the labs’ location. Our system supports the unified exchange of information with third-party applications such as supervisory control systems, LIMS and data historians. Nevertheless, one of the most charming solutions for individual work flow optimisation is the remote control of laboratory devices. The comprehensive Remote Control Suite means that users can remotely observe and control their running parallel bioreactor processes via their PC and Notebook, their Apple Mac and MacBook or even via their iPod and iPhone. This ensures that the efficiency of the systems can be safeguarded even if users are sitting in their office, the institute’s cafeteria or in their gardens at the weekend!