Today, surgical procedures for implanting electronic devices that stimulate the heart muscle to correct abnormal cardiac rhythms are considered routine. But addressing the brain in this way--and reaching areas deep within the cerebral mass without destroying neurons en route--is another matter.
While surgeons have successfully installed electrodes in the brain that have restored a semblance of sight or hearing, stopped the tremors of Parkinson's disease, and cataloged the brain's responses to environmental stimuli, they've always had to break in through the skull. That procedure damages healthy brain tissue, exposes patients to infection, and leaves wires sticking out of their heads. And over time, scar tissue forms around the electrodes, encapsulating them and isolating them from the active brain tissue.
Now a promising new procedure has been proposed [see photo]. In a paper that appeared in the 5 July issue of The Journal of Nanoparticle Research, researchers from the New York University Medical Center, the Massachusetts Institute of Technology, and the University of Tokyo demonstrate how advances in nanotechnology could lead to a better way of getting into the brain. The team, led by Rodolfo Llinas, head of the department of physiology and neuroscience at the NYU Medical Center, in New York City, has devised a method for attaching electrodes to small clusters of brain cells--or even individual neurons--using the cardiovascular system as the conduit through which wires are threaded.
The researchers predict that within a decade or so, it will be possible to insert a catheter into a large artery and guide it through the circulatory system to the brain. Once there, an array of nanowires (wires with diameters on the order of 10-9 meters) would spread into a "bouquet" consisting of millions of tiny probes that could use the 25 000 meters of 10-micrometer-wide capillaries inside the brain as a way to harmlessly reach specific locations within the brain.
In the team's proof-of-concept experiments, they maneuvered 500-nm-diameter platinum wires through the blood vessels in human tissue samples and detected the electrical activity of living brain cells placed adjacent to the tissue. At the same time, they created software and hardware that will likely form a type of analog-to-digital converter, turning signals emitted by the brain into digital signals and vice versa.
"Five years ago, we [at the MIT BioInstrumentation Laboratory] created arrays comprising 100 microelectrodes that [required us] to open the skull and literally punch electrodes into the brain to do recordings," said Patrick Anquetil, a coauthor of the paper who is a Ph.D. candidate at MIT, in Cambridge, Mass. "When we started our collaboration with Professor Llinas and showed him the original work, he was really shocked at how crude a method it was. It was his idea to use the bloodstream, or, in his words, 'the plumbing that is already there.'"
Since then, the challenge has been to create a connector that is small enough at one end to reach any neuron without blocking blood flow, but large enough at the other end (roughly 500 mm) so it can connect with instruments for recording or for delivering pulses of electricity. "That's actually the whole problem with nanotechnology," says Anquetil. "It's actually easy to create these [very tiny] structures, but how do you interface them with our macro world?"
One solution for making this stepping down of wire gauges possible was changing the type of wire. The platinum wires used in the experiments are being phased out in favor of conducting polymers, because they are cheaper, can be turned into much thinner wires, and are more flexible. The team is working on a process to create conducting polymer nanowires as thin as 100 nm.
They believe that a nanowire of this type can also be made steerable so that it could be directed along one of many small blood vessels branching out from a larger one. When a small current is applied to a suitably doped wire, the polymers swell or contract, prompting the wire to bend in a controllable way. The arrangement in the material of dopant (a chemical additive that determines whether the material has the electrical properties of a semiconductor or a conductor) can be electrochemically switched in real time.
What's more, the conducting polymer material is biodegradable, so depending on its composition, it can be implanted for short-term studies or medical diagnostics and will decompose in a manner similar to the sutures used by surgeons to close wounds below the skin. For longer-term connections, such as those that would make possible a through-the-bloodstream cerebral pacemaker for Parkinson's patients, a different polymer formulation would be created from the same set of basic molecular building blocks.
"One of the reasons we're so excited about [these polymers] in the long term is that they are, to our knowledge, the only materials that allow you to build a whole system from the same class of materials," said Anquetil. "Not only can you create wires to transmit information or energy, you can build actuators [to replicate the function of muscles], logic gates for computation, or even sensors."
--Willie D. Jones