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Nanoimprinting process consisting of embossing and RIE etching into resist, intermediate mask layers and substrate. Illustration of imprinting technique using a Si mold. During this process, the pattern of the mold is imprinted 2 and cooled down. After de-molding 3 , the patterns on the Si substrate were heat treated to obtain the final Pd patterns.

During stage 2, there are a few other patterning possibilities: A—C hierarchical patterning can be obtained by using a different Si mold with smaller feature sizes on top of the imprinted Pd benzylthiolate patterns; D—F transfer stacking that is realized by using the Pd pattern and 3 as a substrate; G—I polycarbonate PC transfer that is obtained by using 3 as mold and PC as substrate. Reprinted by permission from Macmillan Publishers Ltd: Radha et al.

Using NIL to create nanoelectrodes allows control of the nanostructure size height, diameter , density, distribution and integration Kuo et al.

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Nanostructure fabrication is flexible in terms of choices of deposition techniques and the substrates on which the deposition takes place insulators, semiconductors or conductors and standard thin film fabrication techniques can be used. There is a need for new device architecture that requires less power and uses smaller surface than the multi-channel devices produced by lithographic patterning. Recently, Rehman and Kamboh reported a novel architecture to amplify the neural signal in implantable brain machine interfaces, which is able to manage both components of the neural signals, i.

Performance metrics could be improved if nanotechology is used to create novel architectures with nanosize features. Because this technology works for more simple nanostructures, the challenge is to finely tune the deposition conditions for creating multi-junction nanostructures using a diameter-controlled synthesis inside the nanopores of a custom made template. An example is the nanofabrication of extracellular electrode array with high density electrical leads such as the low noise multi-channel silicone system Du et al. These results were obtained in awake, behaving, mice by using nanoarrays with a 64 channel silicone-based neural probe.

In the quest to minimize the size and the noise of the system, researchers are searching to decrease the size of neural probes. NIL could be a useful tool to increase the density of recording channels and to achieve high performance recording devices at small scale. Simultaneous recordings of neurons with nanofabricated probes in awake behaving mice.

A Nissl-stained brain section overlaid with a schematic of the probe at its stereotaxically implanted location. Each silicon shaft is 60 mm wide. Scale bar, mm. B Current source density analysis of local field potentials across the hippocampus with a vertical resolution of 28 mm. DG, dentate gyrus.

Neural data was collected during home cage exploratory behavior. Scale bar, ms. C Waveforms of two putative single cells recorded with the nano-probe across all sites together with histograms showing theta phase locking of spikes. Dashed ellipses indicate the sites exhibiting the highest extracellular action potentials for these units. Theta oscillations shown on top of the histograms are for reference. Theta oscillations were measured from the upper rightmost electrode near the CA1 pyramidal cell layer Adapted with permission from Du et al.

Engineering a nanostructure-integrated neuroelectrode represents a particularly difficult challenge: characterization by conventional methods reveals the complexity of materials while in fact the devices are quite simple.

Nanotubes and Nanowires (Nanoscience)

Unconventional physical properties are expected since the crystalline structure depends on the direction of growth. Device performance cannot be exclusively defined by taking the properties of each component and then applying junction theory to them. Instead, a multidisciplinary approach is required.

Given the ability of nanoelectrodes to interact with physiological systems, there is a still work to be done in understanding the relationship between the nanostructure properties and the device properties made from them. Cooperative efforts of many techniques and approaches are required to gain a comprehensive understanding of this relationship.

Additionally, many surface-sensitive techniques have been developed for flat and ultraflat surfaces but not for nanostructures. The tools needed to study the brain must operate at the same nanoscale as brain functions. Huge effort is now devoted to the decoding of specific neural interactions and circuits, a goal that has emerged as the Brain Activity Mapping Project Alivisatos et al. Several examples of the synergy between nanoscience and neuroscience contributions to brain study and brain augmentation are given as follows:.

MEAs add versatility to the real-time, long-term recording of chemical fluctuations in the extra-cellular micro-environment along with neurophysiological activity while being minimally invasive Wise, ; Chang-Hsiao et al. The organization of neural network, its neuronal excitability, and synaptic plasticity, together with drug responses may be monitored by MEAs. Carbon nanotubes CNTs array chips are now used for non-invasive measurement of action potentials, real-time concentration of dopamine, and postsynaptic potentials.

Suzuki et al. These CNTs-MEA chips have been fabricated directly on the microelectrode surfaces by electroplating an indium-tin oxide. Chronoamperometric measurements based on such CNTs-MEA chips detected dopamine concentration at nanomolar level with high temporal resolution and a fold better signal to noise ratio.

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MEA chips may be useful for various applications such as drug screening and toxicity, in vitro stem cell differentiation, synaptic plasticity, or pathogenic processes associated with stroke, epilepsy, Alzheimer's and other neurodegenerative diseases. MEAs using MWCNTs have the advantage of decreased physical size of microelectrode with increased impedance and decreased charge-transfer capability Gacem et al. To decrease impedance, the effective surface area for recording of the electrode needs to be increased.

With a steam-plasma treatment the surface of MWCNTs becomes converted from super-hydrophobic to super-hydrophilic. A multi-walled MEA was employed to record neural signals from a lateral giant cell of an American crayfish.

Synthesis of Inorganic Nanotubes

This electrode type allows the separation of neural signals with their distinct shapes for long-term recordings and improved recording performance. Recent neural probes based on silicon Du et al. MEA uses an application-specific integrated circuit ASIC to intensify signals, multiplexing functions and band-pass filtering.

Multiplex high density devices with a fully integrated low noise, channel system can perform high spatial resolution extracellular measurements and weighs just mg Du et al. Similarly, Viventi et al. This system was employed to record in cat the spatial properties of brain activity in vivo , including patterns of activity like sleep spindles, single-trial visual evoked responses or electrographic seizures.

These developments might provide diagnostic and therapeutic brain-machine interface devices. This electrode has a sensing part made of a thin metal layer deposited on epitaxial grown GaP nanowires. Suyatin et al. Xie et al. The team also has successfully tested the electrode by in vivo recordings in the cortex of rat in multiple brain implantations. This kind of electrode with a controllable geometry of nanowires now can be further used for the investigation of many in vivo functional properties in nanostructured neuronal interfaces.

Current methodologies permit the simultaneous, long-term non-invasive recordings of extracellular field potentials, but not the sub-threshold synaptic potentials that are generated by single cells. Because intracellular recordings of the electrophysiological properties sub-threshold action potentials, synaptic potentials and membrane oscillations can be acquired only by sharp or patch microelectrodes, these recordings may be limited to very short durations and single cells at a time.

An emerging approach in a number of laboratories is based on the merging of the advantages of extracellular microelectrode arrays with those of intracellular microelectrodes Spira and Hai, The neural prostheses that successfully help patients increase their daily living activities are quite simple implants that yield some definite tissue response and are well recognized as foreign body Stieglitz, Based on the latest developments in materials science, new avenues for highly advanced systems to interface the human brain have emerged.

Combinations of neural cells with micro-implants can become the platform of stable bio-hybrid interfaces. Furthermore, converging technologies that exploit synergies between computer sciences and engineering, neuroscience and psychology are envisioned to completely change the understanding of the entire field. Still, the implementation of the neural network type of circuits that are based on non-CMOS complementary metal-oxide-semiconductor memory devices with learning capabilities are rare.

Gacem et al.

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This is possible because the same device ensemble can be trained many times to code successively any type of 3-input combination of Boolean logic functions despite the variability among devices. This approach has huge potential for application to parallel learning of several devices with more complex function. Carbon nanowires used as interface material in contact with neurons can both deliver electrical stimulation to these cells and detect neuronal electrical activity.

Carbon nanowires or nanotubes emerge as materials that do not have recognizable adverse effects. Consequently, they can be successfully used in brain-machine interfaces Malarkey and Parpura, In recent years, research on growing CNT substrates has been used to examine in vivo formation of neurons and neuronal networks during guided growth by artificial nano-scaled cues. Additionally, prostheses for monitoring brain activity were developed using interfaces based on nanotube architecture Stankova et al.

Fabbro et al.

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This observation highlighted the exceptional ability of the CNT substrate to induce nerve tissue growth. They confirmed that CNT scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord and maintained in vitro. Results indicated that spinal neurons plated on electro-conductive CNTs show an assisted expansion.

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  5. These microarray experiments suggest that CNT platforms activate healing activities involving microglia in the absence of reactive gliosis. Imaging applications of CNTs to living cells and tissues bring promising advantages to biological applications based on optical properties of nanotubes. Due to the high photostability of SWCNTs' photoluminescence, a longer excitation time is attainable at higher laser fluency compared to quantum dots or organic fluorophores.

    Also, attenuated absorption combined with autofluorescence and scattering characteristics makes visible the opaque tissue in the range of — nm, while nanotubes allow imaging of the whole blood and thick tissue Heller et al.