The range of length scale in biology varies by several orders of magnitudes—from nanometer sized nucleic or amino acids to several centimeters for organs and neuronal circuits. There is a need for interfaces with nanoscale spatial resolution in order to investigate processes at the subcellular level. Besides carbon nanotubes, these interfaces can be achieved through the use of other nanostructures, such as semiconductor nanowires having dimensions as small as a protein molecule. CNTs and NWs represent the building blocks for nanoscale electronics (McEuen et al. 2002; Lieber 2003). The critical feature sizes (atomic scale) of these building blocks can be well controlled during synthesis, in contrast with the nanostructures fabricated by the “top-down” process. Even for isolated CNTs transistors that have shown exceptional properties (Javey et al. 2003), large scale integration challenges remain due to difficulties in preparing pure semiconductor nanotubes. The issues faced by CNTs could be overcome by nanowires because of the reproducible control over size and electronic properties that current growth methods enable (Cui et al. 2001b, 2003; Cui and Lieber 2001; Wu et al. 2004). A good class of NWs has been developed, ranging from NWs based on classic semiconductors, such as silicon NWs (Chen et al. 2006; Goncher et al. 2006; Yajie et al. 2008), GaP (Dujavova-Laurencikova et al. 2013), GaN (Lee et al. 2007), CdS and ZnS (Barrelet et al. 2003), heterostructures as Ge-Si (Xiang et al. 2006a, b), InAs-InP (Jiang et al. 2007), oxide nanowires MgO (Yin et al. 2002), Cu₂O (Jiang et al. 2002), SiO₂ (Yu et al. 1998; Liu et al. 2001; Zheng et al. 2002), Ga₂O₃ (Wu et al. 2000; Sharma and Sunkara 2002), Al₂O₃ (Valcarcel et al. 1998; Xiao et al. 2002), In₂O₃ (Li et al. 2003), SnO₂ (Dai et al. 2001), MnO₂ (Wang and Li 2002), Sb₂O₃ (Guo et al. 2000), TiO₂ (Seraji et al. 2000; Miao et al. 2002), ZnO (Tian et al. 2003; Vayssieres 2003), LiNiO₂ (Zhou et al. 2002), and others.

The field-effect transistors (FETs) configuration of semiconductor NWs is one of the most appropriate detection schemes for biological events (Cui and Lieber 2001; Cui et al. 2001a, 2003; Zheng et al. 2004; Xiang et al. 2006b). An illustration of a FET schematic is depicted in Fig. 18.2. The binding to the dielectric gate of a polar/charged species appears analogous to applying a voltage to a gate electrode. For example, accumulation of positive carriers (holes) together with an increase/variation in device conductance can be generated by binding a protein with a negative charge to the surface of a p-type FET. Silicon based NWs (or other types of semiconductors) also may function as FET devices (Cui and Lieber 2001; Cui et al. 2003; Lieber 2003; Zheng et al. 2004; Li et al. 2006; Xiang et al. 2006b). One-dimensional morphology of NWs is the main feature that determines overcoming sensitivity limitations for planar FET devices. Thus, a more substantial change in device conductance for the NWs versus a planar FET will take place if any analyte binding event will happen (this event leads to accumulation or depletion of carriers).

One of the most powerful and versatile platforms for building functional interfaces to biological systems (including neurons) is based on NWs devices. NWs are highly local probes for neuronal projections because individual NWs devices are becoming optimal for interfacing with neurons, mainly due to the contact length along the axon, or the dendrite projection crossing a NW, being just about 20 nm. Compared to micro-fabricated electrodes and planar FETs, the active junction area for NWs devices is orders of magnitude smaller.

An important advantage when compared to other electrophysiological methods is the small hybrid junction that is quite similar to natural synapses. This small size creates advantages such as: (a) spatially resolved signal detection without complicated averaging of the extracellular potential, which changes over a large portion of a given neuron, and (b) integration of the axon’s elements together with the dendrite projections from a single cell. The stimulation of neuronal activity through NW/axon junctions is also achievable using NWs devices. Somatic action potential spikes detected with intracellular electrodes are generated by applying excitatory sequences of biphasic pulses to the NWs of NW/axon junctions (Patolsky et al. 2007).

Additionally, a NW-based FET device array can be designed to promote neuron growth (Patolsky et al. 2007). Thus, interfacing ensembles of NWs inputs and outputs to different neuron ensembles enables the implementation of stimulation, inhibition, or reversibly blocking signal propagation through specific pathways allowing the signal flow to be simultaneously mapped throughout the network. Besides single or multiple arrays of NWs-based FET devices used for investigating neuronal activity, the NWs were also used to design and build NWs-based electrodes for neural recordings in the brain.

The potential to revolutionize neuroscience research and clinical therapy (Benabid 2007; Kipke et al. 2008; Vaadia and Birbaumer 2009; Suyatin et al. 2013) is represented by implantable neural interfaces (Rutten 2002; Fromherz 2003; Cogan 2008). However, the recorded neurons and tissue reactions that encapsulate and insulate the implant are still presenting instability results (Schouenborg 2011). The nanostructured electrodes are considered as a promising alternative to conventional neuronal interfaces because the recording properties depend mainly on electrode surface properties and tissue reactions to the surface (Kotov et al. 2009; Timko et al. 2010; Dvir et al. 2011; Suyatin et al. 2013). Nanostructured electrodes provide additional advantages such as improved electrical properties (Keefer et al. 2008; Cellot et al. 2009; Martin et al. 2010; Ansaldo et al. 2011; Duan et al. 2012), a shorter cell-to-electrode distance (Tian et al. 2010; Duan et al. 2012; Xie et al. 2012), and better spatial resolution. They also have a potential for less tissue damage (Almquist and Melosh 2010; Martin et al. 2010; Tian et al. 2010; Duan et al. 2012), better biocompatibility (Hallstrom et al. 2007; Kim et al. 2007; Martin et al. 2010; Berthing et al. 2011) and new functionalities, such as selective guidance of neuronal fibers (Hallstrom et al. 2009). Importantly, recordings of cell signals with different nanowire-based electrodes have been achieved in vitro (Kotov et al. 2009; Tian et al. 2010; Timko et al. 2010; Brueggemann et al. 2011; Dvir et al. 2011; Duan et al. 2012; Robinson et al. 2012; Xie et al. 2012), thus demonstrating that epitaxially grown wires of small diameter may provide a minimally invasive tissue penetration (Kawano et al. 2010; Takei et al. 2010; Tian et al. 2010; Duan et al. 2012; Xie et al. 2012). Until now, using mainly carbon nanotubes without structural feature control and in combination with rather big surfaces, has shown improved cell survival for neuronal interfaces (Hallstrom et al. 2007) and improved cell adhesion with focal adhesions forming specifically on the nanowires epitaxially grown, e.g., gallium phosphide (GaP) NWs have beneficial properties (Prinz et al. 2008). Compared to other material NWs, GaP NWs can be synthesized with very little tapering and exceptional control over their position and geometry, and with a high aspect ratio (the ratio between their length and their diameter) is over 50 (Suyatin et al. 2009). Also, the design and fabrication of a first generation of GaP NW-based electrode with a controllable nanomorphology was reported (Suyatin et al. 2013). The first functional testing in vivo of a NWs based device was performed during acute recordings in the rat cerebral cortex, where the NWs were used as a backbone for metal nanostructured electrode with a three-dimensional (3D) structure. This electrode design opened the development of a new model system, with the prospect of enabling a more reliable tissue anchoring as well as a more intimate contact between the electrode and the neurons (Xie et al. 2010). Further research on the functionality of nanostructure-based neuronal interfaces in vivo is providing better electrode-cell electrical coupling (Hai et al. 2010; Robinson et al. 2012; Xie et al. 2012).

Carbon nanotubes have a multitude of useful properties (electrical, mechanical and chemical) that make them very promising materials for applications in neuroscience. The ease with which carbon nanotubes can be patterned permits use for studying the organization of neural networks while the electrical conductivity of nanotubes can provide a vital mechanism to monitor or stimulate the neurons. Carbon nanotubes can interact with neurons and affect neuronal function, especially at the level of ion channels (Malarkey and Parpura 2007, 2010). Both SWCNTs and MWCNTs have been increasingly used as “scaffolds for neuronal growth”. Recently, CNTs have been used in neural stem cell growth and differentiation research. Also, CNTs have been used as interface materials with neurons, where they can deliver electrical stimulation to these cells and detect electrical activity. Here we mention just few applications of the CNTs:

The tools used to study the functions of the neocortex need to operate at the nano-level, i.e. the same scale as brain functions operate. Nanoscience together with nanotechnology bring together an arsenal of unique methods to examine the complexity of brain function by allowing concurrent recording of thousands of neurons and manipulating the activity of millions of cells. One major reason why we are interested in examining them relates to the fact that they are ideal elements to uncover the micro-connectivity between cortical neurons intra-layer and within cortical minicolumns (Wade and Katzman 1975; Gandhi et al. 2010; Qiu et al. 2010; Choi et al. 2012; Jiang et al. 2013). Huge effort is now being devoted to the decoding of specific neural interactions and circuits, a goal that has emerged as the Brain Activity Mapping Project (Alivisatos et al. 2013). Several examples of the rich synergy between nanotechnology and neuroscience are given as follows: