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Colorized SEM image of the nanowire array. Credit: Integrated Electronics and Biointerfaces Laboratory, UC San Diego

Newly developed nanowires that can record the electrical activity of neurons in detail, may be the key to the next generation of drugs to treat neurological diseases.

A team led by engineers at the University of California San Diego have developed new nanowire technology, which could one day serve as a platform to screen drugs for neurological diseases, enabling  researchers to better understand how single cells communicate in large neuronal networks.

“We’re developing tools that will allow us to dig deeper into the science of how the brain works,” Shadi Dayeh, an electrical engineering professor at the UC San Diego Jacobs School of Engineering and the team’s lead investigator, said in a statement.

Currently 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 caused by difference in ion concentration between the inside and outside of the cell.

This measurement technique is sensitive to small potential changes and provides readings with high signal-to-noise ratio. However, this method is destructive, as it can break the cell membrane and eventually kill the cell. It is also limited to analyzing only one cell at a time, which makes it impractical for studying large networks of neurons, which are how they are naturally arranged in the body.

The novel nanowire technology is nondestructive and can simultaneously measure potential changes in multiple neurons with the same high sensitivity and resolution achieved by the current state-of-the-art technique.

“Existing high sensitivity measurement techniques are not scalable to 2D and 3D tissue-like structures cultured in vitro,” Dayeh said. “The development of a nanoscale technology that can measure rapid and minute potential changes in neuronal cellular networks could accelerate drug development for diseases of the central and peripheral nervous systems.”

How it works

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

The research team recorded the electrical activity of neurons that were isolated from mice and derived from human induced pluripotent stem cells using the nanowires. The neurons survived and continued functioning for at least six weeks while interfaced with the nanowire array in vitro.

The new technology can also 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.

The researchers got past this problem by inventing a new wafer bonding approach to fuse the silicon nanoewires to the nickel electrodes. This approach involved a process called silicidation—a reaction that binds silicon and another metal together without melting either material.

This prevents the nickel electrodes from liquidizing, spreading out and shorting adjacent electrode leads.

While silicidation usually is used to make contacts to transistors, this represents the first time it is being used to do patterned wafer bonding.

“And since this process is used in semiconductor device fabrication, we can integrate versions of these nanowires with CMOS electronics,” Dayeh said.

According to Dayeh, the technology needs further optimization for brain-on-chip drug screening and his team is working to extend the application of the technology to heart-on-chip drug screening for cardiac diseases and in vivo brain mapping. This is still several years away due to significant technological and biological challenges that the researchers need to overcome.

 

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