Neural Tubes

December 10, 2014

I worked in corporate research during the era when corporate laboratories were still bastions of much fundamental research. We had a diverse mix of specialties, including chemistry, physics, computer science, materials science, engineering, and some biotechnology. Such diversity allowed some interesting interdisciplinary studies; and, at one time, a research director espoused the idea of "putting ant brains on a chip."

This was just a vague suggestion, but it encapsulated the idea that Nature had done things in biology that the electronics of the time was having a hard time emulating. Today, the complexity of our microprocessors exceeds four billion transistors, as compared to the three million transistors of the Pentium chips at the time of the "ant brains" suggestion. Today, the path forward seems to rest more clearly on dense integrated circuits and skilled computer scientists and programmers than interfacing to an insect, or animal, brain.

Old school brain interfacing. It must be a serial interface, since only two wires are involved. (Detail of the poster for the 1962 film, "The Brain That Wouldn't Die," by the artist, Reynold Brown, via Wikimedia Commons.)

The brain is composed of neurons, electrically-excitable cells that signal each other through synapses to form the neural network basis of brain function. Aside from the somewhat solvable problem of communicating electrically with neurons, there's the problem of how to mount them on a chip.

Etched channels in glass plates and in other materials have been used to anchor neurons, but the neurons don't behave as they do in the body. Scientists at the University of Illinois at Urbana-Champaign and the University of Wisconsin-Madison have recently created microtubes of silicon nitride that not only act as carriers for neurons, but they also accelerate the nerve cell growth and guide the cell growth direction.[1-3]

This research builds upon the previous development of self-rolled silicon nitride nanotubes at the Micro and Nanotechnology Laboratory of the University of Illinois.[4-5] In work supported by the National Science Foundation and the Office of Naval Research, the laboratory demonstrated self-assembly of on-chip inductors from curled layers of silicon nitride patterned with a metal (see figure).[4-5] The silicon nitride, which is a few tens of nanometers thick, rolls into a tube that hides less than 1% of its original, flat area on the substrate.[5]

A self-rolled inductor starts as a flat layer of silicon nitride on a substrate. Metal traces are added, then one end is detached to allow the layer to curl into a tube, forming an inductor. (Illustration by Xiuling Li)[5]

Arrays of 2.7 - 4.4 micrometer diameter microtubes were formed by the same strain-induced self-rolled-up technology from ultrathin (less than 40 nm) silicon nitride films.[1] These tubes, having been formed from such thin layers, are flexible, so they wrap around the neurons without damaging them. It was found that axons, the long branches that neurons send out to connect with other neurons, grow at a rate that's twenty times faster within the microtubes.[1-2] The research team attributes the enhanced growth rate to adhesion within the tubes, and electrostatic interaction with the silicon nitride.

A photomicrograph of a neuron growing through a microtube. The microtube acts as a soft scaffold for axon growth. (Photo by Xiuling Li)[2]

Says Justin Williams, a professor of biomedical engineering at the University of Wisconsin, Madison, and co-principal investigator of the study,

"It's not surprising that the axons like to grow within the tubes... These are exactly the types of spaces where they grow in vivo. What was really surprising was how much faster they grew. This now gives us a powerful investigative tool as we look to further optimize tube structure and geometry."[2]

Williams also commented on the importance of the research done by University of Illinois graduate student, Paul Froeter, who was also the first author of the study, to mount the transparent microtubes on glass slides,

"Having the ability to see through both the tube and the underlying substrate has been really enlightening... Without this we may have noticed an overall increase in growth rates, but we never would have observed the dramatic changes that occur as the cells transition from the flat regions to the tube inlets."[2]

There she grows! Time lapse images of a neuron growing through a microtube. Reference to the timestamp reveals the enhanced growth rate inside the tube. (University of Illinois image.)[2]

Such guided growth of neurons could enable such things as synthetic neural circuits; and, when stacked in multiple layers, as a scaffold for the growth of nerve bundles. The microtubes could even form a means for restoring the severed nerve connections in spinal cord injury and limb reattachment.[2] One of the next research steps is to place electrodes in the microtubes to allow measurement of the electrical signals in the nerves. This research was supported by the National Science Foundation.[2]

References:

1. Paul Froeter, Yu Huang, Olivia V. Cangellaris, Wen Huang, Erik W. Dent, Martha U. Gillette, Justin C. Williams, and Xiuling Li, "Toward Intelligent Synthetic Neural Circuits: Directing and Accelerating Neuron Cell Growth by Self-Rolled-Up Silicon Nitride Microtube Array," ACS Nano, Article ASAP, October 20, 2014, DOI: 10.1021/nn504876y.
2. Liz Ahlberg, "Microtubes create cozy space for neurons to grow, and grow fast," University of Illinois Press Release, November 11, 2014.
3. Neuron growth through a microotube array, YouTube Video, November 10, 2014.
4. Wen Huang, Xin Yu, Paul Froeter, Ruimin Xu, Placid Ferreira, and Xiuling Li, "On-Chip Inductors with Self-Rolled-Up SiNx Nanomembrane Tubes: A Novel Design Platform for Extreme Miniaturization," Nano Letters, vol. 12, no. 12 (November 21, 2012), pp. 6283-6288 .
5. Liz Ahlberg, "Engineers roll up their sleeves – and then do same with inductors," University of Illinois Press Release, December 13, 2012.