Introduction

HexaScreen^® is an automated multiple minibioreactors system designed specially for the cultivation of animal cells and enabling experiments with a small volume of between 10 and 15 ml, whilst maintaining the main characteristics and technological capabilities of laboratory-size reactors. The HexaBatch version has been developed to carry out 6 experiments in parallel and for on-line monitoring, based on innovative and non-invasive data measurement and acquisition systems, of information about the temperature, dissolved oxygen, pH, optical density and the complete visible spectrum.

The HexaBatch version combines the characteristics of the usual types of experimentation system, such as the ability to carry out several experiments in parallel, single-use technology or small working volumes, with the characteristics of pilot plant and industrial systems, such as homogeneity and continuous process control and monitoring. These characteristics allow:

• Agitation, gas interchange and optimum oxygen supply conditions for the cultivation of animal cells:
  
  • Specialist equipment for the cultivation of animal cells.
  • System suitable for both suspension and adherence cultures.
• Small working volumes:
  
  • The reduced working volumes enable lower working costs in the culture medium...
• Parallel and simultaneous experimentation:
  
  • Time saving, which means faster product development cycles and shorter market-launch times.
  • Reproducible results and statistics.
• On-line and automated measurements for greater precision and control of experiments:
  
  • Real-time kinetic information on cell growth and metabolic activity: cell concentration (OD), dissolved oxygen and pH.
  • No requirements for off-line control or maintenance during the experiment, thus reducing the labour needed and long-duration tasks. 
• Single-use technology to facilitate validation of the experiment:
  
  • No post-experiment treatment requirements, thus saving time and money.
  • Avoids potential cross-contamination.
• Ease of use (inoculate the bioreactors, place them in the work station and obtain the results):
  
  • Expert personnel not needed, results obtained with less effort.
• Optimised culture parameters:
  
  • Easier scaling to laboratory-size reactors.

Description

The HexaBatch cultivation system comprises two distinct parts: the 6 minibioreactors plate and the software-controlled work station.

The minibioreactors plate, made from transparent biocompatible plastic, is equipped with 6 minibioreactors. This plate has been designed for a single use, and is therefore sterilised beforehand in a plastic bag which must only be opened within a sterile area in order to inoculate the minibioreactors. Once the bath has been filled and the minibioreactors inoculated, the plate can be placed inside the workstation. Each minibioreactor is fitted with all the components needed to control the physical conditions and monitor information on the behaviour of the culture. These components include the gas filters, an inoculation septum, miniaturised optical ports for the probes and a magnetic actuator (pendulum) for smooth agitation.

The work station is responsible for providing the right physical conditions to carry out the experiments (temperature, agitation and aeration), also measurement acquisition (optical density, pH and dissolved oxygen) to monitor the behaviour of the cultures.

The general specifications of the HexaBatch version are:

• Multiple single-use polystyrene minibioreactors.
• Culture volume from 10 to 15 ml (x6).
• Connections for data acquisition and control of the work station via Ethernet.
• Controlled variables:
  • Aeration
  • Agitation. Pendular actuator up to 400 rpm, controlled by electromagnets.
  • Minibioreactor temperature. Range from 20 to 40 °C.
  • Aeration system temperature (filters, air...). Range from 20 to 40 ºC.
• Measured variables:
  • Minibioreactor temperature (system functionality information).
  • Aeration system temperature (system functionality information).
  • Optical density (estimation via absorbance spectroscopy, information on total cell concentration via correlation).
  • Dissolved oxygen (estimation via fluorescence measurements, information relating to cell activity).
  • pH (estimation via absorbance spectroscopy, information on cell activity and relating to viable cell concentration).

Accessories & Options

Applications

The HexaBatch version has been designed specifically for cultivating animal cells, including suspension and adherence cultures, although it can be used for cultivating other species such as bacteria and yeasts. The main applications in which the HexaBatch version will have a greater impact include:

• Animal cell cultivation (in suspension and adherent).
• Cell studies: clone selection.
• Cell characterisation: determination of growth parameters (cell concentration, cell activity, growth rate ...).
• Definition and optimisation of the culture medium: comparison of growth between different commercial media, optimisation of the medium composition ...
• Determination of the critical culture parameters.
• Pharmacological tests: therapeutic, toxicity (study of new products), apoptosis ... tests.
• Process optimisation: initial cell concentration, optimum operating conditions for production scaling ...
• Cell adaptation (from adherent cultures to suspension cultures).

At the present time, various cell lines have already been cultivated in the HexaBatch minibioreactors system (see study cases). The HexaBatch minibioreactors platform enables the cultivation of:

• Cell lines in suspension:
  • Hybridomas.
  • CHO cells (adapted to suspension).
  • HEK cells (adapted to suspension).
• Adherent cell lines:
  • Vero cells.
  • Mesenchymal stem cells from sheep.
  • CHO.
  • HEK
• Bacteria:
  • E. coli.
• Yeasts:
  • P. pastoris.

Special Desings