Researchers Grow Brain Cells on a Chip

neuron blob on a scaffold
Photo: Stuart Hay/ANU

Every human thought starts with a signal traveling from one neuron to another in the brain. Yet we know relatively little about how these connections form. In an effort to watch that process unfold, Australian researchers engineered a nanowire scaffold on a semiconductor chip that enables brain cells to grow and form circuits. The scientists described their device recently in the journal Nano Letters

The neural scaffold falls far short of any brain-on-a-chip that futurists might imagine. But it does provide a way for scientists to guide the growth of neurons and study their connectivity, says Vini Gautam, a biomaterials engineer at Australian National University who led the study.

That has been a challenge for scientists trying to recreate neural circuitry in the lab. Neurons in the brain connect and communicate in a highly ordered way. But in the lab, the cells tend to reconstruct randomly and suffer from experimental limitations that render the circuitry nothing like the real thing in the brain. 

“Understanding how neural circuits form in the brain is one of the fundamental questions in neuroscience,” Gautam says. Those connections form the basis for how we process information, and understanding them is key to developing treatments for mental disorders, she says.

Gautam and her colleagues Chennupati Jagadish and Vincent Daria wanted to create an environment where they could both direct the growth of neurons and allow them to make natural, synchronized connections. So they made a nanowire scaffold made of indium phosphide. The semiconductor material is well known for applications in nanoscale electronics such as in the fabrication of LEDs, solar cells. But no one had used it to interface with brain cells, Gautam says.

The researchers arranged the nanowires in a square lattice pattern, placed about 50 neuronal cells from rodents on each scaffold, put it in a culturing medium and watched them grow.

After a few days, the neurons had produced outgrowths called neurites. In the brain, these long, thin structures branch out from the cell body and connect with other neurons at junctions called synapses. On Gautam’s nanowire scaffold, the neurons shot out neurites that branched across the lattice and appeared to link up with other cells through synaptic connections.

“I have a lot of previous experience observing neuronal cells,” where the neurons always grew randomly, Gautam says. “This time when I looked at the scaffold through the microscope, I immediately saw something striking: The neurites of the cells were aligned as a grid in straight lines.”

That’s a good thing, because it means that neurite growth was guided by the topography of the scaffold, giving researchers some control. At the same time, the cells connected naturally, and the communication activity between them was synchronized, as it would be in the brain. Taken together, those attributes make the scaffolds a good platform for studying the biology of neuronal circuits. 

The group monitored the growth using scanning electron microscopy and evaluated the communication between neurons using functional calcium imaging. The cells grew best on scaffolds that had been coated in a thin layer of lysine and laminin—substances that assist with the attachment of cells.

Gautam and her colleagues are now optimizing the scaffolds to better mimic the physical cues of the brain and are using it to investigate the mechanisms involved in the formation of neural circuits. She says she hopes the work will eventually lead to the development of a brain prosthetic that could be used to restore neural circuit formation after injury or disease. 

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Brain on a Chip, DARPA-style

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