My most recent article for the MEMS Investor Journal, titled MEMS FOR NEUROSCIENCE RESEARCH APPLICATIONS, is now available at their website, and reproduced here. The original title, “MEMS on the Brain”, did not make it pass the editor.
An in-vitro study of a neuronal network, with electrodes visible as black squares under the culture, with neuron in green and their nuceli in red. Photo courtesy of 3Brain.
Most articles on MEMS related topics tend to cover large markets in automotive and consumer electronics, not the treatment of debilitating illnesses of the nervous system. But even though the market for neurological applications today is small, MEMS and microfabrication technologies are helping neuroscience researchers in their quest to understand the workings of the brain, advancing knowledge in one of the most exciting fields of scientific endeavor today. And what is more exciting, MEMS technologies are already being deployed in medical devices to treat injuries and diseases of the nervous system, with several products already in human clinical trials and more expected within the next twelve months. Some of these products, quite literally, have neurosurgeons surgically implanting “MEMS on the brain”.
First, some perspective. According to Zack Lynch at the Neurotech Industry Organization, over $150 billion is spent annually on the diagnosis and treatment of diseases of the brain and nervous system. The burden to society of these diseases exceeds one trillion dollars if one includes ancillary costs, such as caring for patients suffering from conditions including Alzheimer’s disease as well as paraplegia and quadriplegia due to a spinal injury.
Central nervous system (CNS) therapeutics are among the most difficult for biotech and pharmaceutical companies to develop. This is partly due to the added difficulty of getting drugs past the “blood-brain barrier”. But another reason is simply that there is just so much yet unknown about the detailed working of the healthy brain and nervous system, and how this changes with injury and disease.
Experimental electrophysiology — stimulating and recording the electrical signals or “action potentials” of neurons (nerve cells) — is a basic technique for studying the nervous system that dates back at least as far as the year 1791 to the work of Galvani stimulating nerves in the legs of frogs. However detailed and precise studies of smaller and more complex networks of neurons require arrays of individual electrodes that are on the order of microns in size. MEMS microfabrication technology is ideal for this. Several academic and commercial groups have adapted existing MEMS technology to microfabricate electrodes, typically made of silicon, platinum or platinum-iridium, partially encased in an insulating material such as polyimide, parylene, or an inorganic dielectric. Examples of such structures are shown in the photos included with this article.
One use of this MEMS technology is to study how neurons and neuronal clusters function in vitro – that is, cells that live outside of the body in a culture dish. This conceptual equivalent of a Petri dish is combined with a two-dimensional array of MEMS based electrodes; neural networks are cultured and can be electrically stimulated and action potentials recorded very precisely. Most current products have 256 individually addressable electrodes; the startup company 3Brain, a new spin-off from the Swiss institute CSEM, recently introduced a product with 4,096 individually addressable electrodes.
A second use of MEMS electrodes is to study brain function in vivo, that is, in living animals — typically rats but sometimes in animals as large as primates. Electrodes are surgically implanted in the brain so that real-time neural activity can be monitored. The University of Michigan spinoff company NeuroNexus is considered a pioneer in this area and provides both single- and multi-electrode products, as is Blackrock Microsystems, tracing its lineage back to the University of Utah. Both companies are so well known in the neuroscience field that paper titles will reference “Michigan probes” and “Utah arrays”. More recently, the European Neuroprobes effort coordinated by IMEC in Belgium and funded by the European Union has developed some innovative products including a three-dimensional electrode arrays.
Neuroscientists routinely use these MEMS based products for “research purposes”, a phrase in the medical world that also implies that they cannot be used in humans. However, several groups and companies are developing MEMS for medical devices meant to be surgically implanted in human patients for treatment of conditions including paraplegia and Parkinson’s disease. This will be the topic of an upcoming article here in the MEMS Investor Journal, which will also include updates from the NIH’s Neural Interfaces Conference, being held this year in Long Beach, California, from June 21 to 23.
