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Directing neurons to form predetermined circuits with the intention of treating neurological disorders and neurodegenerative diseases is a fundamental goal and current challenge in neuroengineering. Until recently, only neuronal aggregates were studied and characterized in culture, which can limit information gathered to populations of cells. In this study, we use a substrate constructed of arrays of strain-induced self-rolled-up membrane 3D architectures. This results in changes in the neuronal architecture and altered growth dynamics of neurites. Hippocampal neurons from postnatal rats were cultured at low confluency (∼250 cells mm–2) on an array of transparent rolled-up microtubes (μ-tubes; 4–5 μm diameter) of varying topographical arrangements. Neurite growth on the μ-tubes was characterized and compared to controls in order to establish a baseline for alignment imposed by the topography. Compared to control substrates, neurites are significantly more aligned toward the 0° reference on the μ-tube arra...

In neural interface platforms, cultures are often carried out on a flat, open, rigid, and opaque substrate, posing challenges to reflecting the native microenvironment of the brain and precise engagement with neurons. Here we present a neuron cell culturing platform that consists of arrays of ordered microtubes (2.7–4.4 μm in diameter), formed by strain-induced self-rolled-up nanomembrane (s-RUM) technology using ultrathin (

An outstanding challenge for humanity is to continue to understand how our brain works and invent technology to restore neural circuit functionalities. Many neural interfaces used for neuron cell cultures are flat, open, rigid, and opaque, posing challenges to reflecting the native microenvironment of the brain and precise engagement with neurons. Here we present a novel neural interface consisting of silicon nitride microtube arrays formed by a new nanotechnology platform that simply relies on strain-induced self-rolled-up membrane (S-RUM) mechanism [1]. We have found that these microtubes provide robust physical confinement and unprecedented guidance effect towards outgrowth of primary cortical neurons [2]. What is more surprising is that a dramatic increase (20x) of the growth rate inside the microtube compared to regions outside the microtubes has been observed [2]. The outgrowth of hippocampal neurons is also explored using identical platforms with the intent of integrating both networks on the same chip. The unique characteristics of these S-RUM microtubes that enabled the cell guidance and acceleration will be discussed in detail: (1) True 3D geometrical confinement: the perfect cylindrical geometry of the S-RUM microtubes with tunable diameters and ultra-thin walls, the same type of small and confined spaces neurons grow in vivo, provides conformal 3D adhesion tailored to different kinds of cells. (2) Electrostatic adhesion: the deposited SiN x thin films are found to have a high density of trapped positive charges that naturally attract the axon towards the microtube opening. The ability of the microtube array to control the speed and direction of axonal extension provides a key element in arranging patterned neural networks that have both short and long range connections. (3) Optically transparent: having the ability to see through both the tube and the underlying substrate enabled direct observation of how cells transition from the flat regions to different parts of the tube.

This study presents the superior structural versatility of strained silicon nitride (SiNx) membranes as a platform for three-dimensional (3D) hierarchical tubular architectures. The effects of compressive and tensile stressed SiNx layer thickness on the self-rolled-up tube curvature, the sacrificial layer etching anisotropy on rolling direction and chirality, and stress engineering by localized thickness control or thermal treatment, are explored systematically. Using strained SiNx membranes as an electrically insulating and optically transparent mechanical support, compact 3D hierarchical architectures involving carbon nanotube arrays and passive electronic components are demonstrated by releasing the functional structures deposited and patterned in 2D. These examples highlight the uniqueness of this platform that exploits 2D processing and self-assembly to achieve highly functional 3D structures.