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Nanowiring for neurons If you want to know what’s going on in a single synapse of the brain, you’ve got to get down to the level of that synapse with your measurement tools. That’s how David Gracias and colleagues at Johns Hopkins University have tackled the problem of measuring local concentrations of an important neurotransmitter, dopamine. In their recent AC paper (DOI 10.1021/ac901744s), the investigators describe long, thin, gold nanowires that can be mass-produced, arranged in any pattern, and integrated with the outside world. “There is much interest in developing smaller electrodes because the normal electrodes used for dopamine detection in the brain are on the micron scale, larger than a synapse,” explains B. Jill Venton at the University of Virginia. She says that, at 30 nm in diameter, the smallest nanowires “in this report are on the scale that could fit in a synapse.” Electrochemical methods for measuring neurotransmitters go back to the 1970s when Ralph Adams at the University of Kansas and his team were demonstrating the ability of small electrodes to monitor neurochemistry. “We’re not reinventing the wheel,” states Gracias. “We’re just miniaturizing [the system] and showing that we can have electrochemical methods at the 30-nm scaleOat this scale, we can measure dopamine at relevant synaptic concentrations.” For instance, the investigators showed that when used for chronoamperometry, the sensors detected submicromolar concentrations of dopamine (the synaptic concentration of dopamine is estimated to be 1.6 mM). Gracias says that, to his knowledge, only one other demonstration has electrochemically measured dopamine at the nanoscale, with carbon nanotubes. But carbon nanotubes can have fabrication issuesOthey have to be grown at high temperatures and they are difficult to integrate with existing systems. In contrast, the gold nanowires that Gracias and colleagues produced are easy to fabricate by lithography and can 2
ANALYTICAL CHEMISTRY /
JANUARY 1, 2010
Optical images of insulated, gold-nanowirebased electrochemical sensors for dopamine, a neurotransmitter implicated in several neurological disorders, including Parkinson’s disease.
be readily insulated and connected to the outside world with a macroscale contact pad. The investigators adapted the fabrication method called lithographically patterned nanowire electrodeposition (LPNE), which was developed by Reginald Penner’s group at the University of California Irvine. The method involves cycles of deposition of various materials and selective etching to let researchers have exquisite control over the dimensions of an object’s features. Using LPNE, Gracias and colleagues could fabricate nanowires with diameters ranging from 30 to 1000 nm, and lengths from 1 to 20 mm. The nanowires were easily integrated and attached to macroscale connectors with alligator clips. As Penner explains, small electrodes demand high, mass-transport-based fluxes to generate currents. “The nice thing about nanowires is you get these high fluxes by shrinking the electrode in just two dimensions. But you leave one macroscopic dimension, and the result is
the currents aren’t in the nano-amp rangeOthey are in the micro-amp range,” he says. “That’s the conceptual leap these investigators have made. They are making micro- and nanoelectrodes out of these wires.” Gracias says it’s the first time gold has been used to make nanowires for the electrochemical detection of dopamine. The metal takes care of a nagging problem in dopamine detection: ascorbic acid. Ascorbic acid is present in high concentrations in synapses and has a similar oxidative potential to dopamine. “A gold electrode is more selective to dopamine than to ascorbic acid, which, in the brain, is a common interfering agent. When you do electrochemical recording, you need to have your electrode more sensitive to dopamine,” explains Gracias. “Otherwise you just measure the background of ascorbic acid.” The investigators discovered another surprising attribute of the nanowires: their sensitivity increased nonlinearly with decreasing diameter. “You would not intuitively think sensitivity necessarily increases with smaller size,” Gracias says, adding that he thinks some interesting diffusion behavior may explain the observation. He’s also encouraged by the phenomenon because it means that when the investigators move to an in vivo experimental system, they will get high sensitivity with the narrowest nanowires at single synaptic junctions. But in gearing up to apply these long, skinny, nanowire-based sensors to an in vivo setting, Gracias and colleagues are anticipating hurdles. For instance, “we have to position our nanowire relative to a single synapse. That is challenging,” Gracias says. “We would need to actually grow the synapse to make it come towards the wire.” The investigators plan on creating neuronal-growthfactor gradients to get the neurons to migrate toward the wire. —Rajendrani Mukhopadhyay
10.1021/AC9025913 2010 AMERICAN CHEMICAL SOCIETY
Published on Web 11/20/2009
