We present preliminary recordings on chip of three-dimensional (3D) electric neuronal activity from cultures of cortical neurons derived from human-induced pluripotent stem cells (hiPSCs). The recordings were obtained through 3D microelectrode arrays (MEAs) composed of truncated, 90 μm-high Si micropyramids endowed with multiple, electrically distinct, and vertically arranged TiN microelectrodes. The unique design and implementation of the 3D microelectrodes, complemented by a 60-electrode readout interface, allow for 3D spatial recording of neuronal activity, as well as single-unit recordings in high throughput, which are currently not possible with commercial MEA platforms. Future work will aim at optimizing extended 3D MEAs over optically transparent substrates for electro-physiological investigation of 3D neuronal tissues and organoids.@en

Continuous monitoring of tissue microphysiology is a key enabling feature of the organ-on-chip (OoC) approach for drug screening and disease modeling. Sensing charged species in OoC tissue microenvironments is thereby essential. However, the inherently small (i.e., cm) size of OoC devices poses the challenging requirement to integrate miniaturized and highly sensitive in situ charge sensing components to maximize signal extraction from small volumes (nL to L, range) of media used in these devices. Here we meet this need by presenting a novel dual-gate field-effect transistor-based charge sensor integrated within an optically transparent microelectromechanical (MEM) OoC device. Post-process mask-less decoration of Ti sensing electrodes by spark-ablated Au nanoparticle films significantly increases the effective electrode surface area and thus sensor sensitivity while retaining the CMOS-compatibility of the wafer-level fabrication process. We validate the biocompatibility of the sensor and its selective response to poly-D-lsine and KC1, and provide a perspective on monitoring cultures and differentiation of hiPSC-derived cortical neurons on our OoC device.@en

Continuous monitoring of tissue microphysiology is a key enabling feature of the organ-on-chip (OoC) approach for in vitro drug screening and disease modeling. Integrated sensing units are particularly convenient for microenvironmental monitoring. However, sensitive in vitro and real-time measurements are challenging due to the inherently small size of OoC devices, the characteristics of commonly used materials, and external hardware setups required to support the sensing units. Here we propose a silicon-polymer hybrid OoC device that encompasses transparency and biocompatibility of polymers at the sensing area, and has the inherently superior electrical characteristics and ability to house active electronics of silicon. This multi-modal device includes two sensing units. The first unit consists of a floating-gate field-effect transistor (FG-FET), which is used to monitor changes in pH in the sensing area. The threshold voltage of the FG-FET is regulated by a capacitively-coupled gate and by the changes in charge concentration in close proximity to the extension of the floating gate, which functions as the sensing electrode. The second unit uses the extension of the FG as microelectrode, in order to monitor the action potential of electrically active cells. The layout of the chip and its packaging are compatible with multi-electrode array measurement setups, which are commonly used in electrophysiology labs. The multi-functional sensing is demonstrated by monitoring the growth of induced pluripotent stem cell-derived cortical neurons. Our multi-modal sensor is a milestone in combined monitoring of different, physiologically-relevant parameters on the same device for future OoC platforms.@en

In vitro study of high-level neurobiological systems requires three-dimensional (3D) neuronal cultures [1]. Meas-uring responses along all three spatial dimensions is critical to record electric activity inside 3D neuronal models, such as organoids and other 3D brain tissue constructs. However, this lies beyond the capacity of 2D microelec-trode arrays (MEAs) [2]. We present planar arrays of 3D micro-pyramids, whereby each micro-pyramid supports multiple, electrically distinct and vertically stacked microelectrodes. The 3D microarrays were produced by wafer-scale micromachining and assembled onto printed circuit boards (PCBs) conforming to MEA readout standards.@en