Automation of a Capillary-Wave Microbioreactor Platform to Enhance Phage Sensitivity Screen Efficiency

To increase their throughput, reduce laboratory work and improve reproducibility, automation of bioprocesses is gaining in importance nowadays. This applies in particular to microbioreactors (MBRs), which can be easily integrated in highly parallelized and automated platforms and, therefore, be applied for screenings, cell-based assays, and bioprocess development. One promising pharmaceutical application for MBRs is the performance of phage sensitivity tests called phagograms in phage therapy. However, there is no automated and parallelized platform available so far that fulfills the requirements of phagograms. Therefore, a novel highly parallelizable capillary-wave microbioreactor (cwMBR) with a volume of 7 µL, which has already been successfully applied for phagograms, was extended by an in-house built platform for automated fluid addition in the single-digit nanoliter range. The cwMBR has a phage-repellent hydrophilic glass surface. Furthermore, a custom-made highly parallelizable device for biomass measurement in the lower microliter scale was developed and validated in the cwMBR. To prove the applicability of the platform for the generation of phagograms, a phagogram using Escherichia coli and automated phage addition was performed. The results indicate a clear lysis of the bacteria by the phages and thus confirm the applicability of performing automated phagograms in the highly parallelizable cwMBR platform.