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ARCHIVED - Brain on a chip

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A new tool will allow scientists to study multiple living cells for weeks or months at a time. Researchers could investigate how communication changes between diseased brain cells, or how they respond to potential drugs.

neurochip.

Canadian scientists have built a revolutionary biochip that promises to further research on neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as heart disease and cancer. Called a neurochip, the new tool can detect electrical signals in groups of connected neurons (brain cells). It could accelerate the development of new drugs and improve our understanding of how neurons communicate and interact.

What is a biochip?

A biochip is a type of microchip that is used to sense either a whole cell or smaller biological entities such as DNA fragments or proteins. The chip works as a sensor and measures chemical reactions, colour changes, electrical activity, or other properties. See bottom of page to find out how researchers use biochips.

This technology is different from other types of biochips in that “we can simultaneously record electrical activity, at a very high level of detail, from several living cells connected in a network,” says Geoff Mealing, an NRC electrophysiologist.

Traditionally, when researchers wanted to measure a cell’s electrical activity, one approach was to grow cell cultures and apply a probe, or “patch-clamp,” with a microscopic head to the membrane of an individual cell. A variation of this approach involves adhering an individual cell to a flat glass surface that has a tiny hole. The probe measures electrical activity by contacting the exposed part of the cell through the hole. But these technologies allow measurements to be done on only one cell at a time.

Dr. Christophe Py inspects a wafer of neurochips.

Dr. Christophe Py inspects a wafer of neurochips.

The NRC neurochip extends the above approach by integrating several probes on a single chip to study multiple living cells over time. Studying groups of cells such as neurons “is a better model of what happens in the brain than looking at just one cell,” stresses Mealing.

“Another fundamental difference between the technology that we’re developing and what’s commercially available is that we’re growing the cells directly on the chip and keeping them alive for extended periods of time,” says Dr. Christophe Py, a semiconductor physicist at NRC. This means scientists could study neuronal networks that are representative of patients with Alzheimer’s or Parkinson’s disease, for example, accelerating the pace of research discoveries.   

The development of this technology required input from a team of biologists, engineers, chemists and other experts. There were numerous puzzles to solve — ranging from how to keep the cells alive and adhere them to the chip to how best to read activity between cells.

With help from the University of Calgary, the NRC team has tested prototype neurochips using snail neurons. “Snail cells are substantially larger than those from a mammal, and easier to work with,” explains Dr. Py.

So far, the researchers have successfully cultured neurons on prototypes and obtained preliminary measurements of synaptic activity between two cells. They are now trying to grow larger numbers of cells on the chips and they plan to work with other types of mammalian cells.

The neurochip was developed with input from NRC biologists, engineers, chemists and other experts. Tanya Comas (left) and Dr. Dolores Martinez (right)

The neurochip was developed with input from NRC biologists, engineers, chemists and other experts. Tanya Comas (left) and Dr. Dolores Martinez (right)

To date, snail cell cultures have survived on the chips for up to two weeks, but the research team anticipates that cells could survive up to several months. This would open the door to studying how neurons change their behaviour over time. For example, scientists could investigate how brain cells are affected by exposure to different chemicals, how communication changes between diseased cells, and how neurons respond to environmental changes or potential drugs. End

Why are biochips helpful for research?

Biochips are used to test how proteins or cells react when exposed to compounds that might be used as potential drugs, to study the behaviour of proteins when exposed to other sorts of chemicals, and more. Biochips are used widely in medical and pharmaceutical research.