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9 Specifications to guide successful Automated sampling in Bioprocessing

Automation and digitisation are becoming increasingly important in the modern environment of bioprocesses 4.0. A new wave of biopharmaceutical manufacturing is already breaking. Driven by the PAT initiative and the goal of a well-understood and optimally controlled process, the digital transformation of bioprocesses is inevitable.

The 3rd Global Bioprocessing, Bioanalytics and ATMP Manufacturing Congress 2020 will focus on the innovative solutions and technologies powering this transformation. One such digital tool is automated sampling.

The introduction to the market of small multi-bioreactors systems using robotic arms for the sampling process is great news. But what to look for in your system and how to choose one?

For bench-top reactors starting with 250 mL volume, a number of systems enabling automated sampling are available on the market. They all share the same basic functionalities – such as the sample draw, maintaining sterility of the bioreactor and sample retention. There are differences between the more advanced functionalities and features. Here are 9 specifications to guide successful implementation of automated sampling in your lab:

1. Sample volume

The available systems take volumes between a few µl and up to 50 mL. Keep in mind that it is most convenient if the automated sampling can be applied for reactors of different sizes (e.g. 250 mL benchtop to 60L pilot scale) and that only the volume needed to analyze your sample should be removed from the bioreactor.

2. Cell removal

Cell removal is a critical step for certain analytics. Each automated sampling system on the market offers a different solution for this challenge. Consider your maximal cell density that must be separated from the cultivation broth. Clogging and cross-contamination are the most common drawbacks and occur more likely with some solutions than with others (e.g. high risk for clogging with conventional membrane probes).

3. Sampling rate

Sampling rates are normally stated by the supplier of the automated sampling system. Keep in mind that these systems are often designed to sample from 8 up to 16 bioreactors consecutively, which impacts the sampling rate for one bioreactor. Only connect as many bioreactors to one system without impairing your required sampling rate.

4. Integration of analyzers

Most suppliers of automated sampling support the integration of analyzers to enable online analytics next to the bioprocess stream. Typically, integrated analyzers are cell counters, enzymatic analyzers to measure substrates and metabolites as well as HPLC systems. An integration requires a fluidic interface to deliver the sample to the analyzer as well as a software interface for triggering the measurement and transferring back the analytical result. Make sure who takes over responsibility for both interfaces – the supplier of the analytical device or the supplier of the automated sampling system. By clarifying responsibility support issues can be solved more easily and faster as you already know whom to contact.

5. Feedback to bioreactor

What should the sampling system do for you? Drawing and processing samples, enable on-line analytics or also do feedback control based on the analytical results?

If you want to do feedback control, there are two major challenges that must be considered: i) the sampling rate and ii) the software interface between the automated sampling system and the bioreactor control.

Regarding the sampling rate you have to clarify how often you need a sample and which time delay is acceptable for your defined control strategy. A daily bolus shot requires only one sample per day and the time delay between the sample draw and the availability of the analytical result is not critical. However, if you want to have a continuous feed both parameters are very critical. The more often a new input is generated for the control, the tighter the control range can be set. Hence, a high sampling rate is needed, and the analytical method should be chosen to be as fast as possible. This way the time delay between sample draw and feedback to the reactor can be minimized.

The second critical point is the software interface. Most automated sampling systems offer OPC to communicate to a SCADA system. However, a precise definition of what is needed should be performed in advance. Should the SCADA only read results from the automated sampling system or should it also be able to send commands (e.g. cancel samples, add new samples etc.). Does the SCADA really get all necessary inputs from the sampling system in order to perform its control task properly? The most convenient solution here is one software that takes over the complete communication between bioreactors, sampling system and the analyzers.

6. Flexibility

Especially in development labs, automated sampling might be used for different processes and for processes showing different requirements for the automated sampling process at the beginning of the process compared to the end of the process. Make sure that the automated sampling system you choose offers the possibility to easily adapt parameters to your needs.

7. Transferability

Automated sampling systems are often first established for small scale bioreactors in process development or strain development labs. However, the system should be easily transferable to a pilot plant or maybe even production scale.

8. Price

The automated sampling systems come in a price range approximately between $ 150 000 to $ 300 000. Apart from the provided functionality, take the consumables and maintenance costs into account when deciding on a system. The consumable costs for cell removal especially vary  between the systems. A simple but easy measure for comparison is the price per sample when using the system. This measure also allows comparing the cost efficiency with manual samples, where the labour hours in the lab should be taken into account as well.

9. Future innovations

Guidelines for pharmaceutical bioprocessing are constantly evolving; especially in the direction of digitalization, automation and process transparency. Hence, also the requirements on automated sampling systems are increasing. It can be beneficial if the supplier of the sampling system has a current development pipeline tackling upcoming challenges.


Alexandra Hofer is business development manager for the automated sampling system Numera at Securecell AG.


Securecell has created an all-in-one solution combining the automated sampling system Numera, with with the Process Information Management Software, Lucullus. The combination enables the sampling process and complete data management from sample trigger to process control with one single software.

Join other leaders in biopharmaceutical production and position your company to play a significant role in the next generation of biopharmaceutical manufacturing and delivery of life-changing medicines at the 3rd Global Bioprocessing, Bioanalytics and ATMP Manufacturing Congress 2020.

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