Neuronal circuits on a chip for biological network monitoring

Abstract

Cultured neuronal networks (CNNs) are a robust model to closely investigate neuronal circuits’ formation and monitor their structural properties evolution. Typically, neurons are cultured in plastic plates or, more recently, in microfluidic platforms with potentially a wide variety of neuroscience applications. As a biological protocol, cell culture integration with a microfluidic system provides benefits such as accurate control of cell seeding area, culture medium renewal, or lower exposure to contamination. The objective of this report is to present a novel neuronal network on a chip device, including a chamber, fabricated from PDMS, vinyl and glass connected to a microfluidic platform to perfuse the continuous flow of culture medium. Network growth is compared in chips and traditional Petri dishes to validate the microfluidic chip performance. The network assessment is performed by computing relevant topological measures like the number of connected neurons, the clustering coefficient, and the shortest path between any pair of neurons throughout the culture's life. The results demonstrate that neuronal circuits on a chip have a more stable network structure and lifespan than developing in conventional settings, and therefore this setup is an advantageous alternative to current culture methods. This technology could lead to challenging applications such as batch drug testing of in vitro cell culture models. From the engineering perspective, a device's advantage is the chance to develop custom designs more efficiently than other microfluidic systems.

Self-organization and evolution of function and structure in cultured neuronal networks

“…Our neuronal cultures, grown on top of MEA plates, show similar self-organization traits than those observed in Petri dishes 23 or in chip devices 51 , that is, randomly scattered neuronal bodies grow new neurites reconnecting among them to finally form a spatial network of interconnected neuronal aggregates similar to the one showed in Fig. 1 a.…”

“…Figure 2 shows the progression of various topological properties of the two network representations, A (panels a-c) and S (panels d-f), of the physical neural circuitry. The longitudinal analysis of the network topology in both cases reveals similar features to those observed in neuronal cultures on Petri dishes 23,45,47,51 . As shown in panels a and d, the number of links increases throughout the maturation process of the CNN, while the total number of nodes (with and without connections) remains stable.…”

Alternative Brain Slice-on-a-Chip for Organotypic Culture and Effective Fluorescence Injection Testing

“…The materials used in this article and their assembly process are based on a previous work [ 41 ], where an organ-on-a-chip composed of glass, vinyl, and PDMS was presented. In this article, these three materials were preserved, and two more components were added—a polycarbonate membrane and a circular PTFE plug (Merck KGaA, Darmstadt, Germany).…”