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Nano- and microtechnology -based analytical devices for online measurements of bioprocesses

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Multiple analyses of bioreactor processes in real-time

Industrial processes exploiting microorganisms are now widely used to produce fuels and pharmaceuticals. EU funded scientists developed an automated monitoring platform to speed process development and increase product quality.

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Advances in gene technology and synthetic biology necessitate also the development of bioreactor cultivations and systems. Fast, high throughput analysis and monitoring of multiple reaction processes or products was previously limited. Scientists initiated the EU funded project 'Nano- and microtechnology -based analytical devices for online measurements of bioprocesses' (NANOBE) to fill this critical gap. NANOBE researchers sought to develop a platform composed of multiple lab-on-a-chip modules for simultaneously analysing many analyte types through in situ sensing and sampling of bioreactor contents. Analytes of interest included individual cells as well as intra- and extracellular components such as metabolites, proteins and enzymes. Scientists chose lactic acid production by the yeast Saccharomyces cerevisiae (S. cerevisiae) as the test case. NANOBE realised numerous technical achievements on the road to the integrated platform, each of which is significant in its own right. Scientists delivered a micro mass spectrometer that is already being marketed. An automated platform for unattended testing for the presence of selected proteins (enzyme-linked immunosorbent assay (ELISA)) was also created. Novel methods were developed for sampling and handling small volumes of fluids, cell counting and sorting, and cell splitting to access intracellular contents. In addition, the team developed two novel optical sensors – one for pH and one for dissolved carbon dioxide (CO2). The wide range of monitoring tools and technology developed within the scope of the NANOBE project resulted in a patent application, 19 publications in peer reviewed journals and 15 conference presentations, as well as expressed interest on the part of end users. Combining developed technology, NANOBE delivered a real time, integrated, automated analytical platform prototype consisting of individual lab-on-a-chip modules for monitoring different bioprocesses. Further testing and optimisation are required to enhance robustness. Nevertheless, these prototypes can potentially decrease development time and costs while increasing product quality. Numerous sectors employing bioreactors stand to benefit, including the pharmaceutical, energy and chemical industries.

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