ARCHIVED - Chips with Neurons Require Brains from Many Disciplines

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February 07, 2007— Ottawa, Ontario

Electronic chips do so much for us in the course of a day, whether it be allowing us to make a cell phone call to anywhere in the world or store video files on a home computer. Imagine how much more they might be able to do if part of those chips were alive, incorporating brain cells as a means of gathering and storing even more information.

A small team of NRC researchers is now exploring this prospect, building partnerships across scientific and technological disciplines, as well as collaborating with new enterprises emerging in this field.

The NRC Institute for Biological Sciences (NRC-IBS) investigators are enticing individual brain cells and very thin sections of brain tissue to grow on the surface of various chip substrates, the kind of silicon wafer that has become so familiar. As these neurons begin to thrive, they re-establish physical connections to one another, building up a synaptic network not unlike that in the brain. At the same time, the underlying substrate can be patterned in ways that guide these connections, encouraging the cells to grow in close proximity to tiny sensors.

Cultured brain (hippocampus) tissue section recorded on a multi-electrode array probe. (Ahuja_IBS-NRC)
Cultured brain (hippocampus) tissue section recorded on a multi-electrode array probe. (Ahuja_IBS-NRC)

These sensors detect the minute electrical signals that cells send or receive throughout the network. Dubbed "neurochips", these devices can reveal much about how neurons function, as well as laying the foundation for a powerful new platform of analytical and diagnostic tools.

"This platform will provide us with highly specific information about what the neurons sense in their environment," says Dr. Danica Stanimirovic, Director of the Neurobiology Program at NRC-IBS. "Based on this, we could use neurochips to look for specific substances in biological fluids, or for toxins. Furthermore, researchers could derive specific information about how drugs interact with the nervous system."

In fact, the most appealing application is a dramatic improvement in the speed and efficiency of drug screening for pharmaceutical research, which requires an understanding of how drug candidate compounds interact with living tissue. Neurochips have the potential to revolutionize this kind of assessment, reporting the electrical or optical activity of these cell networks directly and analysing them with software.

Before such a sensitive and convenient probe can become practical, however, Dr. Stanimirovic and her colleagues have to determine how this kind of functional neurochip would work by developing and testing different prototypes.

"There are several layers of problems, requiring the teaming up of various experts across NRC institutes," she explains. "One issue is biological: how to grow these neurons and complex neuronal structures. Another is finding the materials to support this growth. A third layer is the interface between the cells and materials, which requires engineering skills. And a fourth layer is collecting and analysing the data, which means we need people in information technology."

Multi-electrode array apparatus for long-term recording of electrical activity from brain tissue sections maintained in culture. (Devecseri_IBS – NRC)
Multi-electrode array apparatus for long-term recording of electrical activity from brain tissue sections maintained in culture. (Devecseri_IBS – NRC)

Geoff Mealing, an electrophysiologist in the Synaptic Pathophysiology Group at NRC-IBS, who leads the Neurochip project, has been working with Dr. Stanimirovic to develop partnerships to meet these diverse challenges. An initial "grass roots" effort by several researchers at NRC-IBS and at the NRC Institute for Microstructural Sciences (NRC-IMS) has recently led to combined support from multiple NRC institutes.

As a direct result, a first generation of neurochips is being designed by Christophe Py, a Senior Research Officer in NRC-IMS, with manufacturing to begin soon at the Canadian Photonics Fabrication Centre. The project is also taking advantage of complementary expertise at other NRC institutes, including the NRC Industrial Materials Institute and the NRC Steacie Institute for Molecular Sciences. All four of these NRC institutes will be taking part in an upcoming Neurochip Development Initiative meeting to determine the most effective strategy to move neurochip technology forward.

Other participants include the Heinrich-Heine University of Dusseldorf and several biotech companies, who have formed a "Neurochip Consortium". Among these companies is Ottawa-based QBM Cell Science, which is led by a former NRC postdoctoral fellow, Dr. Anthony Krantis. QBM has developed technology that permits neurons to be frozen and shipped anywhere in the world, where they can be thawed and are as viable as if they had just been harvested. This form of "on demand" supply will be essential to any widespread use of neurochips, but that is only one of the first hurdles.

Mr. Mealing points out that there are many different ways of measuring the tiny electrical signals that represent cell-to-cell communication, including multiple electrophysiological, or optical technologies. The current research in this field is still considering such aspects of the best approach for the design and operation of neurochips. As fundamental as these efforts may be, Dr. Stanimirovic and Mr. Mealing insist that the prospects for the resulting technology remain highly tangible. Quite apart from new devices that could transform existing laboratory procedures, this work promises to shed new light on the most elusive and important properties of neurons.

For Mr. Mealing, what neurochips reveal about brain cells could be as exciting as their application to environmental detection or drug testing. They could answer many of the questions surrounding ailments such as Alzheimer's or Parkinson Disease. He concludes that we may ultimately value this innovation not just because of what it enables electronic chips to do, but for showing us what brain cells have always done.

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