Applications of carbon nanotubes for cancer research

Carbon nanotubes have many unique properties such as high surface area, hollow cavities, and excellent mechanical and electrical properties. Interfacing carbon nanotubes with biological systems could lead to significant applications in various disease diagnoses. Significant progress in interfacing carbon nanotubes with biological materials has been made in key areas such as aqueous solubility, chemical and biological functionalization for biocompatibility and specificity, and electronic sensing of proteins. In addition, the bioconjugated nanotubes combined with the sensitive nanotube-based electronic devices would enable sensitive biosensors toward medical diagnostics. Furthermore, recent findings of improved cell membrane permeability for carbon nanotubes would also expand medical applications to therapeutics using carbon nanotubes as carriers in gene delivery systems. This article reviews the current trends in biological functionalization of carbon nanotubes and their potential applications for breast cancer diagnostics. The article also reports the applications of confocal microscopy for use in understanding the interactions of biological materials such as antibodies on carbon nanotubes that are specific to surface receptors in breast cancer cells. Furthermore, a nanotube-field-effect transistor is demonstrated for electronic sensing of antibodies that are specific to surface receptors in cancer cells.     

Peptide-coated nanotube-based biosensor for the detection of disease-specific autoantibodies in human serum

We demonstrate a label-free peptide-coated carbon nanotube-based immunosensor for the direct assay of human serum. A rheumatoid arthritis (RA)-specific (cyclic citrulline-containing) peptide, was immobilized to functionalized single-walled carbon nanotubes deposited on a quartz crystal microbalance (QCM) sensing crystal. Serum from RA patients was used to probe these nanotube-based sensors, and antibody binding was detected by QCM sensing. Specific antibody binding was also determined by comparing the assay of two serum control groups (normal and diseased sera), and the native unmodified peptide. The sensitivity of the nanotube-based sensor (detection in the femtomol range) was higher than that of the established ELISA and recently described microarray assay systems, detecting 34.4 and 37.5% more RA patients with anti-citrullinated peptide antibodies than those found by ELISA and microarray, respectively. There was also an 18.4 and 19.6% greater chance of a negative test being a true indicator of a person not having RA than by either ELISA or microarray, respectively. The performance of our label-free biosensor enables its application in the direct assay of sera in research and diagnostics.     

Electromechanical and Chemical Sensing at the Nanoscale: Molecular Modeling Applications

Atomistic modeling and simulations are becoming increasingly important in the design of new devices at the nanoscale. Of the myriad of potential application areas commonly associated with Nanotechnology, sensors based on carbon nanotubes (CNT) and metal-oxide nanoribbons are one of the closest to commercial reality. In this work, we review some recent molecular modeling investigations on: (1) CNT-based electromechanical sensors, and (2) gas-sensing properties of SnO² nanoribbons. Simulation methods include: First-Principles Density Functional Theory (DFT), classical molecular mechanics, and Green's-function-based tight-binding transport.     

Coupling of mechanical and electronic properties of carbon nanotubes

Because of the potential importance of carbon nanotubes (CNT) in renewable energy and other fields, molecular orbital ab initio calculations are used to study the relation between mechanical and electronic properties of such structures. We estimate a modulus of elasticity of 1.3 TPa and find out that the mechanism of CNT structure deformation is dependent on their chirality. Armchair and chiral nanotubes have ductile deformation fracture while zigzag have both ductile and brittle; on the other hand armchair nanotubes fracture and form two caps while chiral nanotubes adopt a helical-structure conformation. In addition, the energy gap between occupied and unoccupied molecular orbitals increases when nanotubes are under plastic deformation. This strong coupling between mechanical and electrical properties can be used to tune CNT mechanically to specific electronic bandgaps, affecting directly their electromagnetic absorption properties.     

Can trans-polyacetylene be formed on single-walled carbon-doped boron nitride nanotubes?

Recently, the grafting of polymer chains onto nanotubes has attracted increasing attention as it can potentially be used to enhance the solubility of nanotubes and in the development of novel nanotube-based devices. In this article, based on density functional theory (DFT) calculations, we report the formation of trans-polyacetylene on single-walled carbon-doped boron nitride nanotubes (BNNTs) through their adsorption of a series of C(2)H(2) molecules. The results show that, rather than through [2 + 2] cycloaddition, an individualmolecule would preferentially attach to a carbon-doped BNNT via "carbon attack" (i.e., a carbon in the C(2)H(2) attacks a site on the BNNT). The adsorption energy gradually decreases with increasing tube diameter. The free radical of the carbon-doped BNNT is almost completely transferred to the carbon atom at the end of the adsorbed C(2)H(2) molecule. When another C(2)H(2) molecule approaches the carbon-doped BNNT, it is most energetically favorable for this C(2)H(2) molecule to be adsorbed at the end of the previously adsorbed C(2)H(2) molecule, and so on with extra C(2)H(2) molecules, leading to the formation of polyacetylene on the nanotube. The spin of the whole system is always localized at the tip of the polyacetylene formed, which initiates the adsorption of the incoming species. The present results imply that carbon-doped BNNT is an effective "metal-free" initiator for the formation of polyacetylene.     

Carbon Nanotube‐Silicon Solar Cells

Due to the high cost of silicon photovoltaics there is currently great interest in finding alternative semiconductor materials for light harvesting devices. Single‐walled carbon nanotubes are an allotrope of carbon with unique electrical and optical properties and are promising as future photovoltaic materials. It is thus important to investigate the methods of exploiting their properties in photovoltaic devices. In addition to already extensive research using carbon nanotubes in organic photovoltaics and photoelectrochemical cells, another way to do this is to combine them with a relatively well understood model semiconductor such as silicon. Nanotube‐silicon heterojunction solar cells are a recent photovoltaic architecture with demonstrated power conversion efficiencies of up to ～14% that may in part exploit the photoactivity of carbon nanotubes.     

Controlled patterning of peptide nanotubes and nanospheres using inkjet printing technology.

Peptide nanostructures are expected to serve as a major tool in future nanotechnological applications owing to their excellent self-assembly properties, biological and chemical flexibility and structural simplicity. Yet one of the limiting factors for the integration of peptide assemblies into functional electro-organic hybrid devices is the controlled patterning of their assemblies. Here we report the use of inkjet technology for the application of peptide nanostructures on nonbiological surfaces. The aromatic dipeptides nanotubes (ADNT) which readily self-assemble in solution were used as an 'ink' and patterned on transparency foil and ITO plastic surfaces using a commercial inkjet printer. While inkjet technology was used in the past for the patterning of carbon nanotubes, it was not used for the deposition of biomolecular nanostructures. Furthermore, during the development of the application we were able to produce two types of nanostructures, i.e. nanotubes and nanospheres by the self-assembly of the same aromatic dipeptide, tertbutoxycarbonyl-Phe-Phe-OH (Boc-Phe-Phe-OH), under different conditions. Both spherical and tubular structures could be efficiently patterned on surfaces into predesigned patterns. The applications of such technology are discussed.     

Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.     

Microtubule architecture: inspiration for novel carbon nanotube-based biomimetic materials

Microtubules are self-assembling biological nanotubes that are essential for cell motility, cell division and intracellular trafficking. Microtubules have outstanding mechanical properties, combining high resilience and stiffness. Such a combination allows microtubules to accomplish multiple cellular functions and makes them interesting for material sciences. We review recent experiments that elucidate the relationship between molecular architecture and mechanics in microtubules and examine analogies and differences between microtubules and carbon nanotubes, which are their closest equivalent in nanotechnology. We suggest that a long-term goal in bionanotechnology should be mimicking the properties of microtubules and microtubule bundles to produce new functional nanomaterials.     

Simulations of electrophoretic RNA transport through transmembrane carbon nanotubes

The study of interactions between carbon nanotubes and cellular components, such as membranes and biomolecules, is fundamental for the rational design of nanodevices interfacing with biological systems. In this work, we use molecular dynamics simulations to study the electrophoretic transport of RNA through carbon nanotubes embedded in membranes. Decorated and naked carbon nanotubes are inserted into a dodecane membrane and a dimyristoylphosphatidylcholine lipid bilayer, and the system is subjected to electrostatic potential differences. The transport properties of this artificial pore are determined by the structural modifications of the membrane in the vicinity of the nanotube openings and they are quantified by the nonuniform electrostatic potential maps at the entrance and inside the nanotube. The pore is used to transport electrophoretically a short RNA segment and we find that the speed of translocation exhibits an exponential dependence on the applied potential differences. The RNA is transported while undergoing a repeated stacking and unstacking process, affected by steric interactions with the membrane headgroups and by hydrophobic interaction with the walls of the nanotube. The RNA is structurally reorganized inside the nanotube, with its backbone solvated by water molecules near the axis of the tube and its bases aligned with the nanotube walls. Upon exiting the pore, the RNA interacts with the membrane headgroups and remains attached to the dodecane membrane while it is expelled into the solvent in the case of the lipid bilayer. The results of the simulations detail processes of molecular transport into cellular compartments through manufactured nanopores and they are discussed in the context of applications in biotechnology and nanomedicine.     

Water transport through carbon nanotubes with defects

Non-equilibrium molecular dynamics simulations are performed to investigate how changing the number of structural defects in the wall of a (7,7) single-walled carbon nanotube (CNT) affects water transport and internal fluid dynamics. Structural defects are modelled as vacancy sites (missing carbon atoms). We find that, while fluid flow rates exceed continuum expectations, increasing numbers of defects lead to significant reductions in fluid velocity and mass flow rate. The inclusion of such defects causes a reduction in the water density inside the nanotubes and disrupts the nearly frictionless water transport commonly attributed to CNTs.     

Label-free, chemiresistor immunosensor for stress biomarker cortisol in saliva

Salivary cortisol is commonly used as a bioindicator of the psychobiologic response to environmental and psychological stressors. Current analytical approaches rely on immunoassays performed at distant, centralized laboratories and involve an elaborate specimen collection-processing-transportation-storage-analysis-reporting cycle. To facilitate point-of-use measurement of salivary cortisol levels, we describe the development and proof-of-concept testing of an ultrasensitive, label-free immunosensor based on a single-walled, carbon nanotube-based chemiresistive transducer. Carbon nanotubes were functionalized with a cortisol analog [cortisol-3-CMO-NHS ester] and a monoclonal anti-cortisol antibody was ligated to this receptor. Addition of phosphate buffer as well as artificial saliva spiked with varying cortisol concentrations displaced the anti-cortisol antibody producing corresponding decreases in the resistance/conductance of the nanotube-biomolecule hybrid. The immunosensor demonstrated an ultralow detection limit of 1 pg/ml and excellent binding selectivity for cortisol even in the presence of structurally similar steroids such as 21-hydroprogesterone. The nanotube immunosensor offers attractive prospects for the development of highly sensitive biosensor for rapid, label-free measurement of salivary cortisol in a variety of clinical and research settings.     

Developing implantable optical biosensors

Nanobiotechnologists are developing devices that can measure specific enzymes and proteins. These devices are expected to detect single enzyme or protein molecules accurately, providing highly sensitive biosensing applications. A recent study by Strano and co-workers shows that single-walled carbon nanotubes (SWNTs) hold great promise as implantable biosensors. Although most researchers have focused on substrate-oriented biosensors, Strano and colleagues have shown that the inherent fluorescent properties of suspended individual SWNTs can be used for solution-phase beta-D-glucose sensing.     

Carbon Nanomaterials for Dye‐Sensitized Solar Cell Applications: A Bright Future

There is an urgent need for alternative energy resources due to the rapid rise in the price of fossil fuels and the great danger of the increasing greenhouse effect caused by carbon dioxide emission. Sunlight provides by far the largest of all carbon‐neutral energy sources. Therefore, the current solar‐ or photovoltaic‐cell‐based technologies, which can utilize solar energy, are of extreme importance. Dye‐sensitized solar cells (DSSCs) are of particular interest because they can offer a number of advantages when compared to existing photovoltaic technologies. In this review, recent advances in carbon‐related nanomaterials and their application as materials for DSSCs are discussed. Carbon nanomaterials such as carbon nanotubes and graphene display remarkable electrical, thermal, and mechanical properties that enable several exciting applications in DSSCs. The progress on the utilisation of carbon nanotubes, graphene, and their nanocomposites is reviewed as highly prospective materials to replace transparent conductive oxide (TCO) layers and counter electrodes in DSSCs. Moreover, carbon nanomaterials enable improvement of the performance of absorbing layers in working photoanodes by enhancing the light absorption and electron transport across the semiconducting nanostructured film. The application of carbon nanotubes, graphite particles, and graphene as additives towards the improved efficiency of the electrolyte in these solar cells is also discussed. Finally, a brief outlook is provided on the future development of carbon nanomaterial composites as prospective materials for DSSCs, particularly as components for printable solar cells, which are expected to play an important role in the future solar‐cell market.     

Flexible Supercapacitors Based on Bacterial Cellulose Paper Electrodes

Supercapacitors based on freestanding and flexible electrodes that can be fabricated with bacterial cellulose (BC), multiwalled carbon nanotubes (MWCNTs), and polyaniline (PANI) are reported. Due to the porous structure and electrolyte absorption properties of the BC paper, the flexible BC‐MWCNTs‐PANI hybrid electrode exhibits appreciable specific capacitance (656 F g^?1 at a discharge current density of 1 A g^?1) and remarkable cycling stability with capacitance degradation less than 0.5% after 1000 charge–discharge cycles at a current density of 10 A g^?1. The facile and low‐cost of this binder‐free paper electrode may have great potential in development of flexible energy‐storage devices.     

Theoretical investigations on the functionalization of carbon nanotubes

In this paper, our recent work concerning theoretical studies on the functionalization of carbon nanotubes (CNTs) is reviewed. In particular, two different aspects of the functionalization process are taken into account. On the one hand, the chemical functionalization of the sidewall is exploited as a way to develop nanostructured gas sensing devices. On the other hand, we investigated the possibility of functionalizing the sidewall with transition metal complexes, thus extending the concepts of organometallic chemistry to CNTs. Calculations were performed by applying statical and dynamical (Car-Parrinello) density functional theory methods, as well as hybrid (quantum mechanics/molecular mechanics) schemes. The structural and electronic peculiarities of the CNT model under study, due, for example to the presence of defects, were found to play a crucial role in the modelization of the functionalization process. In most cases, the use of realistic models was essential to achieve a full agreement with experiments.     

High‐Performance Thermoelectric Paper Based on Double Carrier‐Filtering Processes at Nanowire Heterojunctions

As commercial interest in flexible power‐conversion devices increases, the demand for high‐performance alternatives to brittle inorganic thermoelectric (TE) materials is growing. As an alternative, we propose a rationally designed graphene/polymer/inorganic nanocrystal free‐standing paper with high TE performance, high flexibility, and mechanical/chemical durability. The ternary hybrid system of the graphene/polymer/inorganic nanocrystal includes two hetero­junctions that induce double‐carrier filtering, which significantly increases the electrical conductivity without a major decrease in the thermopower. The ternary hybrid shows a power factor of 143 μW m^?1 K^?1 at 300 K, which is one to two orders of magnitude higher than those of single‐ or binary‐component materials. In addition, with five hybrid papers and polyethyleneimine (PEI)‐doped single‐walled carbon nanotubes (SWCNTs) as the p‐type and n‐type TE units, respectively, a maximum power density of 650 nW cm^?2 at a temperature difference of 50 K can be obtained. The strategy proposed here can improve the performance of flexible TE materials by introducing more heterojunctions and optimizing carrier transfer at those junctions, and shows great potential for the preparation of flexible or wearable power‐conversion devices.     

Study of carbon nanotube modified biosensor for monitoring total cholesterol in blood

A carbon nanotube modified biosensor for monitoring total cholesterol in blood was studied. This sensor consists of a carbon working electrode and a reference electrode screen-printed on a polycarbonate substrate. Cholesterol esterase, cholesterol oxidase, peroxidase and potassium ferrocyanide were immobilized on the screen-printed carbon electrodes. Multi-walled carbon nanotubes (MWCN) were added to prompt electron transfer. Experimental results show that the carbon nanotube modified biosensor offers a reliable calibration profile and stable electrochemical properties.     

Efficiency, selectivity, and robustness of nucleocytoplasmic transport

All materials enter or exit the cell nucleus through nuclear pore complexes (NPCs), efficient transport devices that combine high selectivity and throughput. NPC-associated proteins containing phenylalanine–glycine repeats (FG nups) have large, flexible, unstructured proteinaceous regions, and line the NPC. A central feature of NPC-mediated transport is the binding of cargo-carrying soluble transport factors to the unstructured regions of FG nups. Here, we model the dynamics of nucleocytoplasmic transport as diffusion in an effective potential resulting from the interaction of the transport factors with the flexible FG nups, using a minimal number of assumptions consistent with the most well-established structural and functional properties of NPC transport. We discuss how specific binding of transport factors to the FG nups facilitates transport, and how this binding and competition between transport factors and other macromolecules for binding sites and space inside the NPC accounts for the high selectivity of transport. We also account for why transport is relatively insensitive to changes in the number and distribution of FG nups in the NPC, providing an explanation for recent experiments where up to half the total mass of the FG nups has been deleted without abolishing transport. Our results suggest strategies for the creation of artificial nanomolecular sorting devices.