EMU technology: acquisition of Biolector to accelerate bioprocess development for production of vaccines and other molecules of biotechnological interest

Abstract

The development of bioprocesses for production of vaccines and other molecules of biotechnological interest involves several stages from the construction and/or selection of the producer clone to the establishment of cultivation conditions in a bioreactor. After the tedious and critical step of clone selection, one of the most time-consuming steps is the culture medium optimization, normally carried out in flasks using statistical tools as design of experiments (DoE). The Biolector XT microbioreactor will allow accelerating the development of bioprocesses of the associated and complementary projects, skipping the comparatively low informative steps of flask cultures, since this microbioreactor controls pH and dissolved O2, which cannot be controlled in flasks. In addition, the real-time measurement data of biomass, pH, dissolved O2 and fluorescence obtained by the Biolector provide valuable insights into the kinetics of cultivation that are impossible to obtain in flasks. Thus, Biolector allows obtaining data similar to those obtained in a bioreactor by simultaneously evaluating up to 48 cultivation conditions or up to 48 clones at the same time. The microfluidics module associated with the Biolector XT also allows up to 32 parallel cultures to be performed in fed-batch mode, thus providing at the microscale an operation that would normally be carried out only in bioreactors and much later during the bioprocess development and generally with smaller number of variables. Finally, the "O2 Up", "O2 Down", "CO2 Up" and "Anaerobic" regulation modules will allow the cultivation of aerobic, microaerophilic, and anaerobic microorganisms. Also, the O2 Up-regulation module is employed for high cell density cultures of E. coli and yeasts in fed-batch mode at microscale, as it enriches the inlet air with 0-100% pure O2, as it is done in bioreactors. Thus, the acquisition of Biolector XT aims to accelerate the bioprocess development for i) production of vaccines based on recombinant bacillus Calmette-Guérin (rBCG) and vaccines for leptospirosis, Schistosoma mansoni and Streptococcus pneumoniae, ii) for obtaining new therapeutic molecules derived from the salivary gland of Simulium pertinax, iii) production of recombinant antibody fragments obtained in Escherichia coli (anti-TNFa and antibodies for diagnosis and therapy for uropathogenic E. coli infections). The project also aims to accelerate studies of systems biology and metabolic engineering to produce polyhydroxyalkanoate biopolymers, the so-called bioplastics. It is expected that the results of this project will place researchers from the State of São Paulo in the select group of researchers of world excellence who employ the Biolector to maintain a high number of scientific publications in journals with a selective editorial policy, using this equipment for the most varied studies, ranging from the production of recombinant proteins in E. coli and yeast, to biofuels and systems biology and metabolic engineering of microorganisms of biotechnological interest, as well as numerous applications for scale-down and scale-up of various industrial bioprocesses. (AU)