Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neural tissues. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell–derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.

Monitoring dynamic processes in complex cellular environments requires the integration of uniformly distributed detectors within such three-dimensional (3D) networks, to an extent that the sensor could provide real-time information on nearby perturbations in a non-invasive manner. In this context, the development of 3D-printed structures that can function as both sensors and cell culture platforms emerges as a promising strategy, not only for mimicking a specific cell niche but also toward identifying its characteristic physicochemical conditions, such as concentration gradients. We present herein a 3D cancer model that incorporates a hydrogel-based scaffold containing gold nanorods. In addition to sustaining cell growth, the printed nanocomposite inks display the ability to uncover drug diffusion profiles by surface-enhanced Raman scattering, with high spatiotemporal resolution. We additionally demonstrate that the acquired information could pave the way to designing novel strategies for drug discovery in cancer therapy, through correlation of drug diffusion with cell death.

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Three-dimensional cell technologies as pre-clinical models are emerging tools mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neural tissues. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human-induced pluripotent stem cell-derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.