High broadband photoconductivity of few-layered MoS2 field-effect transistors measured using multi-terminal methods: effects of contact resistance.

Among the layered two dimensional semiconductors, molybdenum disulfide (MoS2) is considered to be an excellent candidate for applications in optoelectronics and integrated circuits due to its layer-dependent tunable bandgap in the visible region, high ON/OFF current ratio in field-effect transistors (FET) and strong light-matter interaction properties. In this study, using multi-terminal measurements, we report high broadband photocurrent response (R) and external quantum efficiency (EQE) of few-atomic layered MoS2 phototransistors fabricated on a SiO2 dielectric substrate and encapsulated with a thin transparent polymer film of Cytop. The photocurrent response was measured using a white light source as well as a monochromatic light of wavelength λ = 400 nm-900 nm. We measured responsivity using a 2-terminal configuration as high as R = 1 × 103 A W-1 under white light illumination with an optical power Popt = 0.02 nW. The R value increased to 3.5 × 103 A W-1 when measured using a 4-terminal configuration. Using monochromatic light on the same device, the measured values of R were 103 and 6 × 103 A W-1 under illumination of λ = 400 nm when measured using 2- and 4-terminal methods, respectively. The highest EQE values obtained using λ = 400 nm were 105% and 106% measured using 2- and 4-terminal configurations, respectively. The wavelength dependent responsivity decreased from 400 nm to the near-IR region at 900 nm. The observed photoresponse, photocurrent-dark current ratio (PDCR), detectivity as a function of applied gate voltage, optical power, contact resistances and wavelength were measured and are discussed in detail. The observed responsivity is also thoroughly studied as a function of contact resistance of the device.

Mechanistic Study of the Synergistic Antibacterial Activity of Combined Silver Nanoparticles and Common Antibiotics.

A combination of silver nanoparticles (AgNPs) and an antibiotic can synergistically inhibit bacterial growth, especially against the drug-resistant bacteria Salmonella typhimurium. However, the mechanism for the synergistic activity is not known. This study chooses four classes of antibiotics, ß-lactam (ampicillin and penicillin), quinolone (enoxacin), aminoglycoside (kanamycin and neomycin), and polykeptide (tetracycline) to explore their synergistic mechanism when combined with AgNPs against the multidrug-resistant bacterium Salmonella typhimurium DT 104. Enoxacin, kanamycin, neomycin, and tetracycline show synergistic growth inhibition against the Salmonella bacteria when combined with AgNPs, while ampicillin and penicillin do not. UV-vis and Raman spectroscopy studies reveal that all these four synergistic antibiotics can form complexes with AgNPs, while ampicillin and penicillin do not. The presence of tetracycline enhances the binding of Ag to Salmonella by 21% and Ag(+) release by 26% in comparison to that without tetracycline, while the presence of penicillin does not enhance the binding of Ag or Ag(+) release. This means that AgNPs first form a complex with tetracycline. The tetracycline-AgNPs complex interacts more strongly with the Salmonella cells and causes more Ag(+) release, thus creating a temporal high concentration of Ag(+) near the bacteria cell wall that leads to growth inhibition of the bacteria. These findings agree with the recent findings that Ag(+) release from AgNPs is the agent causing toxicity.

Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles.

Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV. Pfs25 has a complex tertiary structure characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it has been rather difficult to obtain Pfs25 as a homogenous product in native conformation in any heterologous expression system. Recently, we have reported expression of codon-harmonized recombinant Pfs25 in Escherichia coli (CHrPfs25) and which elicited highly potent malaria transmission-blocking antibodies in mice. In the current study, we investigated CHrPfs25 along with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity. The results revealed that CHrPfs25 delivered with various gold nanoparticles elicited strong transmission blocking antibodies and suggested that gold nanoparticles based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens.

Synergistic Antibacterial Effect of Silver Nanoparticles Combined with Ineffective Antibiotics on Drug Resistant Salmonella typhimurium DT104.

Synergistic antibacterial activity of combined silver nanoparticles (AgNPs) with tetracycline (polykeptide), neomycin (aminoglycoside), and penicillin (ß-lactam) was tested against the multidrug resistant bacterium Salmonella typhimurium DT104. Dose-dependent inhibition of Salmonella typhimurium DT104 growth is observed for tetracycline-AgNPs and neomycin-AgNPs combination with IC50 of 0.07 µg/mL and 0.43 µg/mL, respectively. There is no inhibition by the penicillin-AgNPs combination. These results suggest that the combination of the ineffective tetracycline or neomycin with AgNPs effectively inhibits the growth of this bacterium. The synergistic antibacterial effect is likely due to enhanced bacterial binding by AgNPs assisted by tetracycline or neomycin, but not by penicillin.

Cytotoxicity of organic surface coating agents used for nanoparticles synthesis and stability.

Impact on health by nanomaterials has become a public concern with the great advances of nanomaterials for various applications. Surface coating agents are an integral part of nanoparticles, but not enough attention has been paid during toxicity tests of nanoparticles. As a result, there are inconsistent toxicity results for certain nanomaterials. In this study, we explored the cytotoxicity of eleven commonly used surface coating agents in two cell lines, human epidermal keratinocyte (HaCaT) and lung fibroblast (CRL-1490) cells, at surface coating agent concentrations of 3, 10, 30, and 100 µM. Two exposure time points, 2 h and 24 h, were employed for the study. Six of the eleven surface coating agents are cytotoxic, especially those surfactants with long aliphatic chains, both cationic (cetyltrimethylammonium bromide, oleylamine, tetraoctylammonium bromide, and hexadecylamine) and anionic (sodium dodecylsulfate). In addition, exposure time and the use of different cell lines also affect the cytotoxicity results. Therefore, factors such as cell lines used and exposure times must be considered when conducting toxicity tests or comparing cytotoxicity results.

Bio-Conjugated Gold Nanoparticle Based SERS Probe for Ultrasensitive Identification of Mosquito-Borne Viruses Using Raman Fingerprinting.

Dengue virus (DENV) and West Nile virus (WNV) are two well-documented mosquito-borne flaviviruses that cause significant health problems worldwide. Driven by this need, we have developed a bio-conjugated gold nanoparticle (AuNP)-based surface enhanced Raman spectroscopy (SERS) probe for the detection of both DENV and WNV. Reported data demonstrate anti-flavivirus 4G2 antibody conjugated gold nanoparticle (GNP) SERS probe can be used as a Raman fingerprint for the ultrasensitive detection of DENV and WNV selectively. Experimental data show that due to the plasmon coupling in nano-assembly, antibody conjugated GNP- based SERS is able to detect as low as 10 plaque-forming units (PFU)/ml of DENV-2 and WNV, which is comparable with the sensitivity of quantitative PCR-based assays. Selectivity of our probe was demonstrated using another mosquito-borne chikungunya virus (CHIKV) as a negative control. Experimental data demonstrate a huge enhancement of SERS intensity is mainly due to the strong electric field enhancement, which has been confirmed by the finite-difference time-domain (FDTD) simulation. Reported FDTD simulation data indicate the SERS enhancement factor can be more than 104 times, due to the assembled structure. Reported results suggest that bio-conjugated AuNP-4G2 based SERS probes have great potential to be used to screen viral particles in clinical and research-based laboratories.

Inhibition of cytomegalovirus infection and photothermolysis of infected cells using bioconjugated gold nanoparticles.

Human cytomegalovirus (CMV) is a herpesvirus that causes major health problems in neonates as well as in immunocompromised individuals. At present, a vaccine is not available for CMV infection and the available antiviral drugs suffer from toxicity, poor efficacy and resistance. Here, we chemically conjugated a monoclonal antibody raised against CMV surface glycoprotein (gB) with gold nanoparticles (GNP) and characterized the potential of this gB-GNP conjugate for antiviral activity against CMV. The gB-GNP blocks viral replication, virus-induced cytopathogenic effects and virus spread in cell culture without inducing cytotoxicity. High concentrations of gB-GNP that coat the surface of virus particles block virus entry, whereas lower concentrations block a later stage of virus life cycle. Also, cells treated with gB-GNP gain resistance to CMV infection. In addition, infected cells when bound to gB-GNP can be selectively lysed after exposing them to specific wavelength of laser (nanophotothermolysis). Thus, we have not only designed a potential antiviral strategy that specifically blocks CMV infection at multiple stages of virus life cycle, but we have also characterized a technique that can potentially be useful in eliminating CMV infected cells from donor tissue during transplant or transfusion.

Theranostic nanomedicine for cancer detection and treatment.

Cancer is the second leading cause of death in the USA according to the American Cancer Society. In the past 5 years, "theranostic nanomedicine", for both therapeutics and imaging, has shown to be "the right drug for the right patient at the right moment" to manage deadly cancers. This review article presents an overview of recent developments, mainly from the authors' laboratories, along with potential medical applications for theranostic nanomedicine including basic concepts and critical properties. Finally, we outline the future research direction and possible challenges for theranostic nanomedicine research.

Mechanisms of nanotoxicity: generation of reactive oxygen species.

Nanotechnology is a rapidly developing field in the 21(st) century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.

Molecular toxicity mechanism of nanosilver.

Silver is an ancient antibiotic that has found many new uses due to its unique properties on the nanoscale. Due to its presence in many consumer products, the toxicity of nanosilver has become a hot topic. This review summarizes recent advances, particularly the molecular mechanism of nanosilver toxicity. The surface of nanosilver can easily be oxidized by O(2) and other molecules in the environmental and biological systems leading to the release of Ag(+), a known toxic ion. Therefore, nanosilver toxicity is closely related to the release of Ag(+). In fact, it is difficult to determine what portion of the toxicity is from the nano-form and what is from the ionic form. The surface oxidation rate is closely related to the nanosilver surface coating, coexisting molecules, especially thiol-containing compounds, lighting conditions, and the interaction of nanosilver with nucleic acids, lipid molecules, and proteins in a biological system. Nanosilver has been shown to penetrate the cell and become internalized. Thus, nanosilver often acts as a source of Ag(+) inside the cell. One of the main mechanisms of toxicity is that it causes oxidative stress through the generation of reactive oxygen species and causes damage to cellular components including DNA damage, activation of antioxidant enzymes, depletion of antioxidant molecules (e.g., glutathione), binding and disabling of proteins, and damage to the cell membrane. Several major questions remain to be answered: (1) the toxic contribution from the ionic form versus the nano-form; (2) key enzymes and signaling pathways responsible for the toxicity; and (3) effect of coexisting molecules on the toxicity and its relationship to surface coating.

Gold nanocage assemblies for selective second harmonic generation imaging of cancer cell.

Second harmonic generation (SHG) imaging using near infrared laser light is the key to improving penetration depths, leading to biological understanding. Unfortunately, currently SHG imaging techniques have limited capability due to the poor signal-to-noise ratio, resulting from the low SHG efficiency of available dyes. Targeted tumor imaging over nontargeted tissues is also a challenge that needs to be overcome. Driven by this need, in this study, the development of two-photon SHG imaging of live cancer cell lines selectively by enhancement of the nonlinear optical response of gold nanocage assemblies is reported. Experimental results show that two-photon scattering intensity can be increased by few orders of magnitude by just developing nanoparticle self-assembly. Theoretical modeling indicates that the field enhancement values for the nanocage assemblies can explain, in part, the enhanced nonlinear optical properties. Our experimental data also show that A9 RNA aptamer conjugated gold nanocage assemblies can be used for targeted SHG imaging of the LNCaP prostate cancer cell line. Experimental results with the HaCaT normal skin cell lines show that bioconjugated nanocage-based assemblies demonstrate SHG imaging that is highly selective and will be able to distinguish targeted cancer cell lines from other nontargeted cell types. After optimization, this reported SHG imaging assay could have considerable application for biology.

Sensitive and selective detection of trivalent chromium using Hyper Rayleigh Scattering with 5,5'-dithio-bis-(2-nitrobenzoic acid)-modified gold nanoparticles.

Hyper Rayleigh Scattering (HRS) and absorption spectral assays using surface-modified gold nanoparticles (AuNP) have been developed for sensitive and selective detection of trivalent chromium (Cr3+) from other metal ions including hexavalent chromium (as Cr2O72-). Gold nanoparticles of 13 nm, covalently attached with 5,5'-dithio-bis-(2-nitrobenzoic acid) (AuNP-DTNBA), is used as a probe for both the absorption and HRS assays. AuNP-DTNBA is able to detect Cr3+ at 20 ppb level at pH 6.0 using absorption spectral change of the AuNP-DTNBA. Visible color change can be observed when mixed with 250 ppb of Cr3+, while there is no color change when mixed with 2 ppm level of some of the most common metal ions such as Cr2O72-, Hg2+, Ba2+, Fe3+, Pb2+, Na+, Zn2+, Cd2+, Co2+, Mn2+, Ca2+, and Ni2+. However, a color change is observed when mixed with Ni2+, Zn2+, and Cd2+ at a concentration higher than 2 ppm. The detection limit for the HRS assay is on a remarkable 25 ppt level, and there is no detectable HRS signal at 2 ppm level for Cr2O72-, Hg2+, Ba2+, Fe3+, Pb2+, Na+, Zn2+, Cd2+, Co2+, Mn2+, Ca2+, and Ni2+.

Enhanced Photodynamic Selectivity of Nano-Silica-Attached Porphyrins Against Breast Cancer Cells.

The synthesis and characterization of bare silica (4 nm in diameter) nanoparticle-attached meso-tetra(N-methyl-4-pyridyl)porphine (SiO(2)-TMPyP, 6 nm in diameter) are described for pH-controllable photosensitization. Distinguished from organosilanes, SiO(2) nanoparticles were functionalized as a potential quencher of triplet TMPyP and/or singlet oxygen ((1)O(2)) at alkaline pH, thereby turning off sensitizer photoactivity. In weak acidic solutions, TMPyP was released from SiO(2) surface for efficient production of (1)O(2). By monitoring (1)O(2) luminescence at 1270 nm, quantum yields of (1)O(2) production were found to be pH-dependent, dropping from ~ 0.45 in a pH range of 3-6 to 0.08 at pH 8-9, which is consistent with pH-dependent adsorption behavior of TMPyP on SiO(2) surface. These features make bare SiO(2)-attached cationic porphyrin a promising candidate for use in PDT for cancer treatment in which efficient (1)O(2) production at acidic pH and sensitizer deactivation at physiological pH are desirable. The enhanced therapeutic selectivity was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests and trypan blue exclusion tests of cell viability in breast cancer cell lines. Bimolecular quenching rate constants of (1)O(2) by free TMPyP, SiO(2) and SiO(2)-TMPyP nanoparticles were also determined.

Imidazole-modified porphyrin as a pH-responsive sensitizer for cancer photodynamic therapy.

5,10,15,20-Tetrakis(N-(2-(1H-imidazol-4-yl)ethyl)benzamide)porphyrin produced twice as many singlet oxygen ((1)O(2)) molecules at pH 5.0 (quantum yield 0.53 ± 0.01) than at pH 7.4, whereas the (1)O(2) quenching rate was reduced by a factor of 2.5 for a pH change from 7.4 to 5.0.

A label-free gold-nanoparticle-based SERS assay for direct cyanide detection at the parts-per-trillion level.

Cyanide is an extremely toxic lethal poison known to humankind. Developing rapid, highly sensitive, and selective detection of cyanide from water samples is extremely essential for human life safety. Driven by the need, here we report a gold-nanoparticle-based label-free surface-enhanced Raman spectroscopy (SERS) system for highly toxic cyanide ion recognition in parts-per-trillion level and to examine gold-nanoparticle-cyanide interaction. We have shown that the SERS assay can be used to probe the gold nanoparticle dissociation process in the presence of cyanide ions. Our experimental data indicates that gold-nanoparticle-based SERS can detect cyanide from a water sample at the 110 ppt level with excellent discrimination against other common anions and cations. The results also show that the SERS probe can be used to detect cyanide from environmental samples.

Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria.

Nanometer-sized gold, due to its beautiful and bountiful color and unique optical properties, is a versatile material for many industrial and societal applications. We have studied the effect of gold nanoparticles on Salmonella typhimurium strain TA 102. The gold nanoparticles in solution prepared using the citrate reduction method is found not to be toxic or mutagenic but photomutagenic to the bacteria; however, careful control experiments indicate that the photomutagenicity is due to the co-existing citrate and Au³âº ions, not due to the gold nanoparticle itself. Au³âº is also found to be photomutagenic to the bacteria at concentrations lower than 1 µM, but toxic at higher concentrations. The toxicity of Au³âº is enhanced by light irradiation. The photomutagenicity of both citrate and Au³âº is likely due to the formation of free radicals, as a result of light-induced citrate decarboxylation or Au³âº oxidation of co-existing molecules. Both processes can generate free radicals that may cause DNA damage and mutation. Studies of the interaction of gold nanoparticles with the bacteria indicate that gold nanoparticles can be absorbed onto the bacteria surface but not able to penetrate the bacteria wall to enter the bacteria.

Structure, bonding, and linear optical properties of a series of silver and gold nanorod clusters: DFT/TDDFT studies.

DFT/TDDFT calculations have been carried out for a series of silver and gold nanorod clusters (Ag(n), Au(n), n = 12-120) whose structures are of cigar-type. Pentagonal Ag(n) clusters with n = 49-121 and hexagonal Au(n) clusters with n = 14-74 were also calculated for comparison. Metal-metal distances, binding energies per atom, ionization potentials, and electron affinities were determined, and their trends with cluster size were examined. The TDDFT calculated excitation energies and oscillator strengths were fit by a Lorentz line shape modification, which gives rise to the simulated absorption spectra. The significant features of the experimental spectra for actual silver and gold nanorod particles are well reproduced by the calculations on the clusters. The calculated spectral patterns are also in agreement with previous theoretical results on different-type Ag(n) clusters. Many differences in the calculated properties are found between the Ag(n) and Au(n) clusters, which can be explained by relativistic effects.

Rapid colorimetric identification and targeted photothermal lysis of Salmonella bacteria by using bioconjugated oval-shaped gold nanoparticles.

Salmonella bacteria are the major cause for the infection of 16 million people worldwide with typhoid fever each year. Antibiotic-resistant Salmonella strains have been isolated from various food products. As a result, the development of ultrasensitive sensing technology for detection and new approaches for the treatment of infectious bacterial pathogens that do not rely on traditional therapeutic regimes is very urgent for public health, food safety, and the world economy. Driven by this need, we report herein a nanotechnology-driven approach that uses antibody-conjugated oval-shaped gold nanoparticles to selectively target and destroy pathogenic bacteria. Our experiments have shown the use of a simple colorimetric assay, with an anti-salmonella antibody conjugated to oval-shaped gold nanoparticles, for the label-free detection of S. typhimurium with an excellent detection limit (10(4) bacteria per mL) and high selectivity over other pathogens. When bacteria conjugated to oval-shaped gold nanoparticles were exposed to near-infrared radiation, a highly significant reduction in bacterial cell viability was observed due to photothermal lysis. Ideally, this nanotechnology-based assay would have enormous potential for rapid, on-site pathogen detection to avoid the distribution of contaminated foods.

Influence of the central metal ion on nonlinear optical and two-photon absorption properties of push-pull transition metal porphyrins.

We present a quantum-chemical analysis of the central metal ion's effect on first hyperpolarizabilities and two-photon absorption (TPA) cross sections at the infrared region of a series of push-pull porphyrins whose synthesis and NLO properties have been reported earlier (J. Am. Chem. Soc. 2005, 127, 9710). The molecular geometries are obtained via the B3LYP/6-31G(d,p) level optimization including SCRF/PCM approach, and the NLO and TPA properties are calculated with the ZINDO/CV method including solvent effects. It is found that the CT transition between the metal ion's d orbital and the macrocycle pi orbitals plays an important role on NLO and TPA properties of metal porphyrins. Our data suggest a new approach to enhance TPA properties of porphyrin materials. We also present a quantum-chemical analysis on porphyrin dimers and trimers to understand the relationship between structural and collective NLO properties. It has been observed that beta values can be improved about an order of magnitude and TPA properties can be enhanced by 2 orders of magnitude by the formation of a trimer. The importance of our results with respect to the design of photonic and photodynamic therapy materials have been discussed.

Effect of conjugation path length on quadratic nonlinear optical properties of monomer and aggregates of zwitterionic merocyanine dyes.

We present a quantum-chemical analysis of the conjugation path length effect on first hyperpolarizabilities of a series of zwitterionic merocyanine dyes whose synthesis has been reported earlier (J. Am. Chem. Soc.2002, 124, 9431, J. Am. Chem. Soc. 1997, 119, 3144). The effect of the conjugation path lengths is evaluated to demonstrate the engineering guidelines for enhancing molecular optical nonlinearity. The first hyperpolarizabilities are calculated for extended conjugated monomer and H and J type aggregates of merocyanine dyes, to provide insight into the intermolecular interactions and the relationship between structural and collective nonlinear optical properties. The molecular geometries for monomers are obtained via B3LYP/6-31G(d,p) level optimization including the SCRF/PCM approach, and the dynamic nonlinear optical (NLO) properties for monomer and aggregates are calculated with the ZINDO/CV method, including solvent effects. It is found that the chain length dependence of the first nonlinearity peaks at n = 6 and then it starts changing slowly for monomer and aggregates of zwitterionic merocyanine dyes. It is concluded that an excellent NLO response in solution might vanish when the active chromophore forms higher H aggregates. The importance of our results on the design of electrooptic materials has been discussed.