LTCC-Based Multi-Electrode Arrays for 3D in Vitro Cell Cultures

Current technologies to monitor neuronal cultures in vitro are based on 2-dimensional (2D) multi-electrode arrays and cell cultures. The complexity of actual high-level neurobiological systems requires 3-dimensional (3D) cultures and 3D electrode arrays to improve our understanding of such systems. The realization calls for smart multilayer and packaging technology. Our approach uses low-temperature cofired ceramics (LTCC) for the design of a 3-dimensional multi-electrode array (3D MEA). An LTCC multilayer board with gold electrodes forms the basis of the system. The layout of the 3D MEA is designed to fit into widely used measurement adapters for 2D signal recordings, enabling data processing identical to that of established chips. Design and manufacturing of the new 3D device as a basic tool for the investigation of 3D cell cultures are described. Features of thick-film gold electrodes are characterized by means of microscopic and spectroscopic tools complemented with complex impedance measurements. Possible biological applications for in vitro electrophysiological measurements were evaluated based on cell cultures of primary neurons, seeded directly to the chip surface. It was shown that activity can be measured over six months.