Nanotechnology coming to a brain near you

(Nanowerk Spotlight) If you have seen the movie The Matrix then you are familiar with 'jacking in' - a brain-machine neural interface that connects a human brain to a computer network. For the time being, this is still a sci-fi scenario, but don't think that researchers are not heavily working on it. What is already reality today is something called neuroprosthetics, an area of neuroscience that uses artificial microdevices to replace the function of impaired nervous systems or sensory organs.

Different biomedical devices implanted in the central nervous system, so-called neural interfaces, already have been developed to control motor disorders or to translate willful brain processes into specific actions by the control of external devices. These implants could help increase the independence of people with disabilities by allowing them to control various devices with their thoughts (not surprisingly, the other candidate for early adoption of this technology is the military).

The potential of nanotechnology application in neuroscience is widely accepted and an indication of where nanotechnology can be used in the future. Especially single-walled carbon nanotubes (SWCNT) have received great attention because of their unique physical and chemical features, which allow the development of devices with outstanding electrical properties.

In a crucial step towards a new generation of future neuroprosthetic devices, a group of European scientists developed a SWCNT/neuron hybrid system and demonstrated that carbon nanotubes can directly stimulate brain circuit activity.

Examples of existing brain implants include brain pacemakers, to ease the symptoms of such diseases as epilepsy, Parkinson's Disease, dystonia and recently depression; retinal implants that consist of an array of electrodes implanted on the back of the retina, a digital camera worn on the user's body, and a transmitter/image processor that converts the image to electrical signals sent to the brain; and most recently, cyberkinetics devices such as the BrainGate™ Neural Interface System that has been used successfully by quadriplegic patients to control a computer with thoughts alone.

Where will nanotechnology take us in this field? Thanks to the application of recent advances in nanotechnology to the nervous system, a novel generation of neuro-implantable devices is on the horizon, capable of restoring function loss as a result of neuronal damage or altered circuit function. The field will very soon be mature enough to explore in vivo neural implants in animal models.

"We developed an integrated system coupling SWCNTs to an ex vivo reduced nervous system, where a mesh of SWCNTs deposited on glass acts as a growing substrate for rat cultured neurons" Dr. Maurizio Prato and Dr. Laura Ballerini explain to Nanowerk. "We demonstrated that neurons form functional healthy networks in vitro over a period of several days and developed a dense array of connection fibers, unexpectedly intermingled with the SWCNT meshwork with tight contacts with the cellular membranes.

Ballerini, an associate professor in Physiology, and Prato, a professor in the Department of Pharmaceutical Science both at the University of Trieste, Italy, are also involved in the European Neuronano project, an advanced scientific multi-disciplinary project to develop neuronal nano-engineering by integrating neuroscience with materials science, micro- and nanotechnology. The Neuronano network's major aim is to integrate carbon nanotubes with multi electrode array technology to develop a new generation biochips to help repair damaged central nervous system tissues.



"For the first time, we show how electrical stimulation delivered through carbon nanotubes activates neuronal electrical signaling and network synaptic interactions" says Dr. Michele Giugliano , a researcher at the Brain Mind Institute at the Ecole Polytechnique Federale de Lausanne in Switzerland. He is one of Ballerini's co-authors of their recent paper "Interfacing Neurons with Carbon Nanotubes: Electrical Signal Transfer and Synaptic Stimulation in Cultured Brain Circuits" . "We developed a mathematical model of the neuron/SWCNT electrochemical interface. This model provides for the first time the basis for understanding the electrical coupling between neurons and SWCNT."



Over the past few years, there has been tremendous interest in exploiting nanotechnology materials and devices either in clinical or in basic neurosciences research. However, so far the interactions between carbon nanotubes and cellular physiology have been studied and characterized as an issue of biochemical mechanisms involving molecular transport, cellular adhesion, biocompatibility, etc. These new findings boost scientists' understanding of interfacing the nervous system with conductive nanoparticles, at the very fast time scale of electrical neuronal activity which in mammals determines behavior, cognition and learning.

"Recently, the Neuronano research group pioneered the exploration of carbon nanotubes as artificial means to interact with the collective electrical activity emerging in networks of vertebrate neurons" says Giugliano. "Biocompatibility of carbon nanotubes has been shown in the literature and several groups recently have attempted coupling neurons to carbon nanotubes to probe or elicit electrical impulses. However, specific considerations of the electrophysiological techniques that are crucial for understanding signal-transduction and electrical coupling were underestimated."

The researchers achieved direct SWCNT?neuron interactions by culturing rat hippocampal cells on a film of purified SWCNTs for 8?14 days, to allow for neuronal growth. This neuronal growth was accompanied by variable degree of neurite extension on the SWCNT mat. A detailed scanning electron microscopy analysis suggested the presence of tight interactions between cell membranes and SWCNTs at the level of neuronal processes and cell surfaces

"With regards to the technological processes involved in the SWCNT deposition on glass, the chemical processes we previously developed and used in this work is the only one effectively employing no intermediate functional group to anchor the carbon nanotubes to the glass substrate, thus allowing a unique perspective of the properties and interaction of nanotubes alone" says Prato.

The scientists point out that their results as a whole represent a crucial step towards future neuroprosthetic devices, exploiting the surprising mechanical and (semi)conductive properties of carbon nanotubes. This field is now closer to a quantitative understanding of how precise electrical stimulation may be delivered in deep structures by 'brain pacemakers' in the treatment of brain diseases.