title: Toward intelligent synthetic neural circuits: directing and accelerating neuron cell growth by self-rolled-up silicon nitride microtube array.
abstract: 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 (<40 nm) silicon nitride (SiNx) film on transparent substrates. These microtubes demonstrated robust physical confinement and unprecedented guidance effect toward outgrowth of primary cortical neurons, with a coaxially confined configuration resembling that of myelin sheaths. The dynamic neural growth inside the microtube, evaluated with continuous live-cell imaging, showed a marked increase (20×) of the growth rate inside the microtube compared to regions outside the microtubes. We attribute the dramatic accelerating effect and precise guiding of the microtube array to three-dimensional (3D) adhesion and electrostatic interaction with the SiNx microtubes, respectively. This work has clear implications toward building intelligent synthetic neural circuits by arranging the size, site, and patterns of the microtube array, for potential treatment of neurological disorders.
authors.affiliation: Department of Electrical and Computer Engineering, Micro and Nanotechnology Laboratory, ‡Department of Bioengineering, and §Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Froeter
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Olivia V
authors.initials: OV
authors.lastname: Cangellaris
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.forename: Erik W
authors.initials: EW
authors.lastname: Dent
authors.forename: Martha U
authors.initials: MU
authors.lastname: Gillette
authors.forename: Justin C
authors.initials: JC
authors.lastname: Williams
authors.forename: Xiuling
authors.initials: X
authors.lastname: Li
mesh_terms: D002455:Cell Division; D005453:Fluorescence; D008855:Microscopy, Electron, Scanning; D016571:Neural Networks, Computer; D009474:Neurons / Q000166:cytology*; D017655:Silicon Compounds
chemical_list: D017655:Silicon Compounds; C032734:silicon nitride
keywords: axon guidance; neural culture; neural-electrode interface; pathfinding; silicon nitride nanomembrane