Collaboration EloSystems and KIWI-biolab, TU Berlin

Collaboration EloSystems and KIWI-biolab

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Collaboration EloSystems and KIWI-biolab, TU Berlin

In the frame of a PhD project of Lucas Kaspersetz at the KIWI-biolab, Chair of Bioprocess Engineering at TU Berlin, the new instrument of EloSystems – „µCheck“ – a smart system for online monitoring of bacteria in bioprocesses was tested in E. coli cultivations.

These E. coli fed-batch cultivations were conducted in a robotic small scale bioreactor system with 8 parallel running cultivation vessels of 100 mL fermentation volume (Cultivation system HEL BioXplorer 100). The cultivation system was integrated into a liquid handling station (LHS Tecan Evo 150) for automated cultivation workflows. The aim of these parallel cultivations was to investigate the responses of E. coli related to recombinant protein production under glucose oscillations and temperature shifts.

The µCheck “classic” device was used in combination with the bypass module, functioning as a gas bubble separator, for the online measurement of OD, cell size (length), and cell concentration in these E. coli cultivations. With a special optical flow cell, processes up to OD 60 can be tracked online without dilution or sampling. In these cultivations, OD values of up to 45 were obtained. At OD > 60, a dilution option is available allowing measurements in high cell density cultivations of up to OD 200 in automatic operation.

Results of the online measurements with µCheck in E. coli parallel cultivations:
– Good correlation was achieved between the biomass and reference measurements (at-line).
– Significant changes in cell morphology due to exposure to stress were observed with the µCheck device.

Conclusions of the feasibility study for the new measurement device:
– Wide concentration ranges can be covered without sample loss due to the the design of the narrow flow cell -> suitable for aerobic, heavily gassed systems.
– The residence volume in the bubble separator will be further improved to allow the use in a small scale with parallel-operated cultivation vessels from approx. 10-20 mL sample volume.

(EloSystems GbR and Chair of Bioprocess Engineering are Bio-PAT members.)

About the µCheck System

The μCheck system is used for online monitoring of cell size during the growth of bacteria in suspension culture. Measurement of cell concentration and biomass is also integrated into the μCheck system. The μCheck is suitable for real-time analysis of bacterial cells and chains in the size range 0.8 μm to 40 μm. Analysis is performed in flow-through mode without sampling, directly in the growth medium under sterile conditions.

The multiparametric system is designed for short- or long-term cultivation of bacterial species such as E. coli, Lactobacillus sp., Bifidobacterium sp., Corynebacterium sp., Ralstonia, Bacillus sp., Listeria sp., and many others. Continuous analysis with μCheck can be used for all types of cultivation methods (anaerobic, aerobic, batch, fed-batch)

A μCheck-D version with integrated dilution function is available as a special model for aerobic high-cell density cultivations. Due to the integrated dilution procedure and the optimised measuring technique, the analysis system is able to determine optical densities above 300 in real-time.

The μCheck system can be connected to any culture vessel or bioreactor using pre-fabricated sterile disposable tubing sets. μCheck has an integrated syringe pump and valves for precise sequencing of measurements and intermediate rinsing of the measurement zone. The aseptic design of the fluidic components and the closed sample loop without the necessity to draw a sample and interfer with the process.

The μCheck system is almost maintenance-free. Due to its small size, it can be placed flexibly in the process environment. For connection to the bioreactor, the user has the proven connectors (sterilisable or disposable) and the bypass module at his disposal. Thanks to the structured design and the simple operating concept, routine analysis can be carried out after only a short instruction

μCheck can be operated as a stand-alone system or via a compact PC using the supplied software. For use with a PC, the unit is connected to the PC by means of communication interfaces (USB, Bluetooth). In addition, the measurement data is automatically stored on an internal memory card and can be retrieved separately if required. The μCheck software is suitable for parallel operation of up to four μCheck units. A tested compact PC with pre-installed software for visualisation and data management will be supplied.

For validation and routine verification of the measurement system, reference samples of bacterial cultures are available. The pre-tested batches of starter and probiotic cultures are long-time stable when stored. The average cell size (length) of these reference cultures is in the range between 2.0 and 6.0 μm. The μCheck optical measurement unit can also be easily validated using the OD standards supplied.

Areas of application

  • Production of recombinant proteins and other biosubstances
  • Production of starter cultures, probiotic and competent cells
  • Development and production of vaccines, infection biology
  • High-cell density fermentation processes
  • Quality assurance and process validation of bacterial cultivations
  • Long-term studies of bacterial evolution
  • Many other fermentation strategies


  • Automatic, real-time determination of
    – Cells and cells chain size
    – Cells concentration
    – Biomass (via OD measurement)
  • Online analysis directly in the growth environment
  • Acquisit of a large numbers of cells for statistically validated
  • Smart system, easy-to-use by routine cultivations
  • Suitable for culture development, monitoring and prediction
  • Selection of optimal growth media and feeding strategy
  • Suitable for batch, fed-batch, anaerobic and aerobic cultivation
  • Operating with small, bench and pilot scale bioreactors
  • Ideal for the use in parallel processes
  • Excellent price/performance ratio

More information on the µCheck-device can be found HERE.