Neuron-reading nanowires

Accelerating the development of drugs for neurological diseases

December 19, 2017

neuron

A breakthrough in nanowire technology is enabling researchers to dig deeper into the science of how the brain works, and help identify the most effective drugs for neurological diseases.

New non-destructive technology

The team, led by Shadi Dayeh, an electrical engineering professor at the UC San Diego Jacobs School of Engineering, has developed nanowires that can record the electrical activity of neurons in fine detail, allowing researchers to better understand how single cells communicate in large neuronal networks.

The key differentiator? The new nanowire technology is nondestructive and can simultaneously measure potential changes in multiple neurons—with the high sensitivity and resolution achieved by the current state of the art.

The new device consists of an array of silicon nanowires densely packed on a small chip patterned with nickel electrode leads that are coated with silica. The nanowires penetrate cells without damaging them and are sensitive enough to measure small potential changes that are a fraction of or a few millivolts in magnitude.

Researchers can uncover details about a neuron’s health, activity and response to drugs by measuring ion channel currents and changes in its intracellular potential. These are due to the difference in ion concentration between the inside and outside of the cell.

This is in contrast to the existing high sensitivity measurement technique. It was ultimately destructive, breaking the cell membrane and eventually killing the cell. It was also limited to analysing only one cell at a time, making it impractical for studying large networks of neurons. And it was not scalable to 2D and 3D tissue-like structures cultured in vitro.

Wafer bonding innovation

Another innovative feature of this technology is it can isolate the electrical signal measured by each individual nanowire.

“This is unusual in existing nanowire technologies, where several wires are electrically shorted together and you cannot differentiate the signal from every single wire,” Dayeh said.

To overcome this hurdle, researchers invented a new wafer bonding approach to fuse the silicon nanowires to the nickel electrodes. They used a process called silicidation, which is a reaction that binds together two solids (silicon and another metal) without melting either material. This prevents the nickel electrodes from liquidising, spreading out and shorting adjacent electrode leads.

Researchers have used the new nanowire technology to record the electrical activity of neurons that were isolated from mice and derived from human induced pluripotent stem cells. These neurons survived and continued functioning for at least six weeks while interfaced with the nanowire array in vitro.

Dayeh noted that the technology needs further optimisation for brain-on-chip drug screening. “Our ultimate goal is to translate this technology to a device that can be implanted in the brain.”

“We envision that this nanowire technology could be used on stem-cell-derived brain models to identify the most effective drugs for neurological diseases,” said Anne Bang, director of cell biology at the Conrad Prebys Center for Chemical Genomics at the Sanford Burnham Medical Research Institute.

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