SOMETIMES our bodies are just too clever for their own good. Whether the object is to overcome a disability, or to use our thoughts to control machines around us, there’s a major obstacle to creating an interface between brain and machine: our ever-alert immune system. Even the most effective immunosuppressant drugs cannot stop it piling up cells around an electrode and walling off the intruder from the very neurons it is trying to contact. Whenever surgeons remove implanted electrodes – which frequently stop working within a few weeks – they find them covered in a layer of immune cells.
Now David Martin, a materials engineer at the University of Michigan, has found a way of making the invading electrodes seem a little less hostile. His trick is to give them a furry coat. “Cells are little living objects,” he points out. “They like things that feel nice.” Simplistic as this sounds, the evidence is building up that Martin’s touchy-feely approach really works.
In the past year, Ravi Bellamkonda and colleagues at Case Western Reserve University in Cleveland, Ohio, have found that the difference in hardness between biological tissue and a foreign material has a big influence on the strength of the immune response. The greater the difference, the stronger the immune response, they reported in October at the US National Institutes of 91ɫƬ Workshop on Neural Prosthetics. So as the human brain is a million times softer than the silicon used to make many implanted electrodes, it’s no wonder the immune system responds so vigorously to their presence.
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In Martin’s initial attempts to make electrodes seem less foreign to living tissue, he used polymers based on the proteins in spider silk. Using an electric field to control a fine jet of a solution containing the protein, he piled the protein molecules onto the surface of an electrode. Protein molecules landing on the silicon surface emerge from solution and link up with one another to form a polymer chain, leaving the electrode wrapped in a fine fuzz.
To see how these polymer-coated electrodes would fare when implanted into rat brains, Martin teamed up in 2001 with pathologist Patrick Tresco at the University of Utah in Salt Lake City. The results were striking. When the team removed the electrodes several weeks after they had been implanted, a clump of living brain tissue came out with them, attached by a network of spidery neurons that had grown into the furry coating. Control electrodes without the polymer coating came out covered with nothing more than a thin film of immune cells.
It was promising proof of the fur coat principle. But there were still practical problems to overcome. Examining the electrodes closely, Martin could see that the neuron growth did not extend up to the surface of the electrode – an essential requirement for good electrical contact. This seemed to be because the fuzzy protein was only loosely attached. There was still an abrupt change in hardness at the electrode’s surface, and this acted as a barrier to neurons. What was needed was something that would grow thick, dense hair right from the electrode’s surface.
Armed with this insight, Martin began to experiment with conducting polymers – plastics that conduct electricity but are hundreds of times softer than silicon. Although these materials are not good enough conductors to act as probes in their own right, Martin figured they could mediate between the hardness of the electrode and the softness of the brain.
Polypyrrole, a soft, conducting polymer often used in antistatic coatings for wrapping electronics, seemed to Martin to be a good candidate. If you put a charge on the electrodes while the polypyrrole is forming, one end of the growing polymer chain will cling electrostatically to the electrode surface.
Ideally, these hairs should stick out of the electrode, inviting neuron growth towards the conducting surface. One of Martin’s graduate students, Mohammad Abidian, suggested that the best way to achieve this would be to use gel – hydrogel, to be precise. Hydrogels are networks of polymers that strongly attract water molecules, which cluster along every fibre in the material. This makes the polymer network soft and pliable – thus ideal for use alongside biological tissue – and an excellent scaffold for supporting the polymer hairs.
Abidian suggested coating the electrodes with a hydrogel seeded with the pyrrole units that make up polypyrrole. If a charge is then placed on the electrodes as the pyrroles polymerise, which happens whenever they come in contact with water, the resulting polymer molecules stick onto the electrode surface like soft fur growing from a skin. They tried it, and it worked. Within a few days, another of Martin’s students, Donghwan Kim, had produced microscope pictures of a thick fur coating the electrodes.
But when Martin’s team tried implanting the coated electrodes, they hit another problem. The coating was so weak it came away from the surface as the electrode was pushed into living tissue. And even when the coating survived implantation, the hydrogel turned out to be impenetrable. Its strong surface tension meant that, like pond skaters sitting on water, neurons simply couldn’t get under its skin. For several months, the hydrogel idea seemed to have hit a dead end.
Now Martin has come up with a strategy that deals with both these problems: get tough before you get fluffy. He makes up the hydrogel-pyrrole mixture as normal and then freeze-dries it on the electrode. This leaves a tough coating that easily survives the implantation procedure. Although the drying breaks up the polymerised pyrrole into its constituent units again, the pyrrole units that were electrostatically bonded to the electrode remain in place. Once inside living tissue, the gel reinflates and the pyrrole re-polymerises to form the furry coating.
This trick also helps neurons to get inside the hydrogel. The freeze-drying process creates fissures and cracks in the coating, which provide a route for neurons to grow into the reinflated hydrogel. Martin and Tresco are currently testing the new inflatable gel in rats. So far they only know that it successfully reinflates in situ.
Martin is also looking at ways to improve the electrical connection between the conducting polymer and the neurons. In conducting polymers, as in metals, current is carried by the movement of electrons. But in neurons, it is the movement of waves of ions in and out of cells that carries the current. “The critical event is the transfer of electrons from the device to ions in the brain,” says Martin. Biological cells are covered with nanoscale fuzz formed by clusters of membrane proteins. Martin’s initial results show electrical charge is transferred more efficiently if the surface texture of the furry electrodes is matched more closely to that of living tissue.
So far no one knows exactly what the surface texture of neurons is like, but Martin is finding out by creating different kinds of fuzz on his electrodes. He does this by using surfactants — chemicals like washing-up liquids that create bubbles in water – to create water bubbles in the hydrogel. Different-sized bubbles cause the polypyrrole to polymerise on different scales, producing fuzz of different textures. By comparing the way these various coatings transfer charge to neurons, Martin hopes to pin down the scale of neural fuzz and create the perfect electrical interface for biological tissue. Then at last, thanks to a nanoscale fur coat, the cyborg revolution can begin in earnest.