Tunnels for neurons to guide brain-electronics interface studies
(Nanowerk Spotlight) Brain-computer interfaces, neural probes, brain implants – they all require intensive in vivo studies on how to best combine inorganic electronics with organic neurons (see for instance "Nanotechnology to repair the brain"). Currently, most neural culture studies suffer from the fact that their cells migrate on a flat surface and are directly exposed to the culture solution, which do not reflect the microenvironment in vivo – neurons, though, can alter their behaviors dramatically in response to the environment change. Ideal cultures, therefore, should mimic the native neural microenvironment to capture the normal cell behavior.
This has motivated a group of researchers at the University of Wisconsin-Madison, led by Robert Blick and Justin Williams, to come up with this a semiconductor nanomembrane tube approach, which provides a 3D confinement that can potentially isolate the cells from the culture solution. Since these tubes are made from a semiconductor material, it means that they can be integrated with electronic functionalities such as voltage sensors.
"We fabricated arrays of semiconductor tubes using strained silicon and germanium nanomembranes and employed them as a cell culture substrate for primary cortical neurons," Minrui Yu tells Nanowerk. "Our experiments show that the silicon-germanium substrate and the tube fabrication process are biologically viable for neuron cells. We also observe that neurons are attracted by the tube topography, even in the absence of adhesion factors."
Here, they show that neurons can be guided to pass through the tubes during outgrowth, leading to defined neuronal networks.
Arrays of semiconductor tubes can guide neuron outgrowth (through the tube) and signal propagation (shown as lightnings) among them. (Image: Minrui Yu, University of Wisconsin-Madison)
"The tube diameter reported in our paper is still big compared to the neural processes, or neurites" says Yu. "Ideally we want to keep it between 1 to 3 micrometers, which is a range relevant to neuronal cell culture applications. This way we can achieve a tight wrapping around the neurites and hopefully isolate them from the extracellular solution. Currently we are working with our materials science colleagues to grow materials that can provide tubes with the right size. Our initial results show tubes with such sizes do not affect neuron outgrowth."
There are several interesting aspects in this work:
the finding that silicon-germanium, as a semiconductor material, can actually support neural cell culture;
the fabrication of micrometer-sized tubes with this material and the observation that neurons seem to be attracted by the tubular topography to the extent that their outgrowth is guided by the tubes;
a printing technology that allows putting neurons close to the entrance of a tube so that a single axon – which is like a long tail projecting from the cell body and helps to pass electrical signals from the cell – can be isolated and grow into and through the tube.
"Our findings suggest a promising approach in the study of neuro-semiconductor interface – not only is it possible to bring electronics close to the cell, but also can we control the neurons to grow into a predefined network in such a way that the axon can be potentially shielded by the tube" Says Yu. "The latter point is important because that is what it looks like in vivo, where the axon is ensheathed by a dielectric material called myelin. Actually our calculations show that the semiconductor tube resembles the myelin, both physically and electrically."
Fluorescent microscopy and SEM images of cortical neurons cultured on a silicon wafer with Si/SiGe tubes. (a) Pseudocolored fluorescent image of neurons growing extensively on an array of patterns, which consist of multiple extending tubes on each side. Inset is a SEM picture of the pattern. The fluorescent image, is taken using antibody to tubulin that heavily labels dendrites and axons. Semiconductor structures are invisible in the fluorescent image, but are outlined by the contrast of surrounding fluorescently labeled neurons and processes, as shown inside the white circle. (b) SEM image of neurons at an intersection of several tubes. Neurons appear to grow processes in the entire area, although more concentrated in the vicinity of the tubes. Scale bar is 100 µm for (a) and 10 µm for (b). (Reprinted with permission from American Chemical Society)
Since our tube mimics the natural myelin, researchers might be able to use them to investigate myelin-related neurodegenerative diseases such as multiple sclerosis. The knowledge gained from studying the neuro-electronic interface can also help in the design of future neuroprosthetic devices.
"As the potential applications suggest, the ultimate goal of our study is to apply this technology in vivo" Yu points out. "Before that, we have to answer important questions such as the material biocompatibility, how to implant devices like this into the body, and any long term effects."