Superior neuronal outgrowth guidance and rate enhancement using silicon nitride self-rolled-up membranes

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.