Microfluidic trapping of 3D spheres in microfluidic reaction systems for real time biosensing of flow chemistry derived compounds

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The topic of the research project of the 2nd funding period will be the combination of a 3D organoid based multiparametric real time biological activity monitoring and the adaptation of the microfluidic lab-on-chip design (1st funding period). Coupling an inline real time bioanalysis under a high degree of environmental control for the bioelectronic monitoring of complex 3D cell aggregates under flow will be the challenge. During the 1st funding period we were successful in establishing a fast, sensitive real time analytical tool based on viable 2D cell monolayer for impedimetric monitoring of chemical synthesis educts/products with regard to biological activity. Now the on-chip microfluidic trapping of 3D organoids i.e. organotypic cardiac spheres that recapitulate the in vivo situation will be the main research topic. The drug discovery shall be realized on a microfluidic chip consisting of two levels (i) for the microsynthesis area, the µFFE field and the microchannels connecting the 3D microcavity-electrode as a multi-well format on the (ii) second level including positioning channels for the 3D cultures. The novel microcavity array structures (200 – 500 µm length, 130-330 µm depth) with at least four electrodes per microcavity will be produced in fused silica substrates using the innovative technology of selective laser etching. These integrated microcavity structures on the multilevel microfluidic chip will be contacted by a hybrid multiplexer electronic board, which is based on the impedance multiplexer board developed during the 1st funding period. For the synchronous multimodal measurement of the biological targets, the electronic board will be extended by an electronic module for the field potential recording. The extended multimodal system comprises, a switch between impedance spectroscopy, field potential recording, and photonic monitoring of 3D cardiac clusters under fluidic conditions, which allows to analyse physiological biomechanical and electrophysiological properties in real-time. Thus, the microfluidic chip for viable cell monolayer from the 1st funding period will be extended by a novel module for 3D organoid trapping and real time hybrid live-sensing of 3D spheres in microcavity arrays based on experiences demonstrated in the past.