Micro Bioreactor - High-Throughput Fermentation

BioLector  - the most advanced micro-bioreactor platform for high speed bioprocess development.

  • 48 parallel high-throughput bioreactors 
  • Online monitoring
  • Microfluidic Bioprocess control
  • Disposable platform
  • Scalabilty


             
From Micro-Bioreactor to Process
The most advanced micro-bioreactor platform for high speed bioprocess development.
High-Throughput Fermentation
Microfluidic Bioprocess Control Plates
High Oxygen Mass Transfer Plates
Measuring up to 6 parameters simultaneously

Synthetic Biology and new promotors

Application example: Screening of promotor libraries

Source: http://2010.igem.org/Team:DTU-Denmark/SPL_Section

Our BioLector® technology can be applied in synthetic biology to study the physiological behaviour of synthetic bugs. By changing the metabolic pathways, growth behaviour and acidification, the microorganism can be affected in designing a new bioprocess. Our micro-bioreactor technology processes all these new bugs under different fermentation or media conditions in a high-throughput manner and with online monitoring. 
BioLector® is very often used for the basic characterization of new promotors or even whole libraries of synthetic promotors by using fluorescent proteins (e.g. GFP) as reporters.

Microtiter Plates

FlowerPlate® & Round Well Plate

Measurement positions in FlowerPlate® for incubation in BioLector®

The FlowerPlate® is a new microtiter plate which combines unique mass transfer performance with online measurements of the most relevant fermentation parameters. Based on a standard SBS footprint the flower geometry was picked out of more than 30 different well geometries. The flower shape acts similar like baffles in shake flasks and increases dramatically mixing and gas/liquid mass transfer. Its perfomance surpasses all common microtiter plates formats providing a unique solution for cell growth and other biocatalytic reactions.
The FlowerPlate® is optimized for orbital shakers with a 3 mm orbit as well as for the powerful BioLector® andRoboLector® technology.
A unique performance:
- Wide volume range (800 – 1500 µL)  
- Effective mixing 
- High mass transfer: kLa > 600 h-1 (OTR > 100 mmol/L/h) 
- Reduced spilling 
- No optical cross talk 
- No foaming  
- Continuous contact of liquids to optodes 
- Multiparameter reading possible  
- Scalability to production fermenters
Additionally m2p-labs offers the Round Well Plate as 48 deep well microplate for shear-sensitive organisms like mammalians or mycelia. The Round Well Plate also includes all features of the FlowerPlate® like broad range of filling volumes (1500 – 2400 µL) and online monitoring of most important fermentation parameters in combination with the powerful BioLector® technology.

Clone Screening

The screening of clones often resembles a lottery. The more clones can be screened, the better are your chances to find the optimization desired. The BioLector® allows for high-throughput screening of clones as well as the detection of relevant metabolic information including biomass, pH-value, dissolved oxygen and fluorescence detection of proteins or dyes. This enables rapid and informed strain improvement and development.

Application example: Screening of 96 GFP expressing H. polymorpha clones in parallel

Source: Kensy et al. (2009) Microb. Cell Fact. 8:31

Bioprocess Development

Traditional methods of screening and process development often have limitations. These include the inability of lab scale methods to be predictive of performance at larger scale, throughput and amount of information. The BioLector® is a superior tool for all of these reasons. With the geometry of theFlowerPlate® and the shaking capabilities of the BioLector®, a broad range of defined oxygen transfer rates can be achieved, permitting an easy scalability to bench, pilot and production scales. While bench scale fermenters can produce a large amount of bioprocess information, throughput and the runnable number of fermentations at once are limited. Using methods like shake flasks can increase throughput, however, the amount of information that can be collected is low. Also, cultivations must be paused for sampling which can affect gas transfer and culture performance negatively. The BioLector® can run 48 fermentations in parallel, while measuring up to 6 parameters at the same time including biomass, pH, dissolved oxygen and fluorescence such as proteins or dyes. While measuring, the plate continues to shake to avoid any pause in gas transfer to the culture. Time between measurements is very short, 20 min at maximum, allowing small inflections in the biomass profile, which may indicate metabolic changes, to be observed.

Application example: Scalability as prequisite for bioprocess development at µ-scale

Source: Rohe et al. (2012) Microb. Cell Fact. 11:144

Anaerobic Fermentations

BioLector® can accommodate both of these trends in bioprocess development. The BioLector® can run 48 fermentations in parallel, while measuring up to 6 parameters at a time including biomass, pH, dissolved oxygen and fluorescence such as proteins or dyes. With the use of our anaerobic cultivation chamber, the 48 well plate can be prepared in an anaerobic hood, transported to the BioLector® and cultivated all while remaining completely anaerobic. The 48 well plate is sealed into the chamber for transport and a low flow of nitrogen blankets the small chamber headspace during cultivation.
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Media Optimization

Many nutrient components can be experimented with, but also their interactions, to optimize the most productive and cost-efficient media. The high-throughput nature of the BioLector® enables Design of Experiments (DoE) to be easily managed and executed.
When using conventional methods for media optimization, measurements are taken every couple of hours as is limited by sampling. If an inflection is observed in a curve, the typical assumption made is an operator error in dilution or measurement. However, with the BioLector®, measurements are taken so frequently (20 min at maximum) that inflections in a measurement curve can be trusted to be a change in metabolism such as diauxic shift or nutrient limitation.

Application example: Determination of minimum phosphate demand

Source: Huber et al. (2011) BMC Biotechnol. 11:22

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