Plasmonic-Magnetic Active Nanorheology for Intracellular Viscosity.

We demonstrate active plasmonic systems where plasmonic signals are repeatedly modulated by changing the orientation of nanoprobes under an external magnetic field, which is a prerequisite for in situ active nanorheology in intracellular viscosity measurements. Au/Ni/Au nanorods act as "nanotransmitters", which transmit the mechanical motion of nanorods to an electromagnetic radiation signal as a periodic sine function. This fluctuating optical response is transduced to frequency peaks via Fourier transform surface plasmon resonance (FTSPR). As a driving frequency of the external magnetic field applied to the Au/Ni/Au nanorods increases and reaches above a critical threshold, there is a transition from the synchronous motion of nanorods to asynchronous responses, leading to the disappearance of the FTSPR peak, which allows us to measure the local viscosity of the complex fluids. Using this ensemble-based method with plasmonic functional nanomaterials, we measure the intracellular viscosity of cancer cells and normal cells in a reliable and reproducible manner.

Bioelectronic Skin Based on Nociceptive Ion Channel for Human-Like Perception of Cold Pains.

A bioelectronic skin device based on nociceptive ion channels in nanovesicles is developed for the detection of chemical cold-pain stimuli and cold environments just like human somesthetic sensory systems. The human transient receptor potential ankyrin 1 (hTRPA1) is involved in transmission and modulation of cold-pain sensations. In the bioelectronic skin, the nanovesicles containing the hTRPA1 nociceptive ion channel protein reacts to cold-pain stimuli, and it is electrically monitored through carbon nanotube transistor devices based on floating electrodes. The bioelectronic skin devices sensitively detect chemical cold-pain stimuli like cinnamaldehyde at 10 fm, and selectively discriminate cinnamaldehyde among other chemical stimuli. Further, the bioelectronic skin is used to evaluate the effect of cold environments on the response of the hTRPA1, finding that the nociceptive ion channel responds more sensitively to cinnamaldehyde at lower temperatures than at higher temperatures. The bioelectronic skin device could be useful for a basic study on somesthetic systems such as cold-pain sensation, and should be used for versatile applications such as screening of foods and drugs.

Ion-Selective Carbon Nanotube Field-Effect Transistors for Monitoring Drug Effects on Nicotinic Acetylcholine Receptor Activation in Live Cells.

We developed ion-selective field-effect transistor (FET) sensors with floating electrodes for the monitoring of the potassium ion release by the stimulation of nicotinic acetylcholine receptors (nAChRs) on PC12 cells. Here, ion-selective valinomycin-polyvinyl chloride (PVC) membranes were coated on the floating electrode-based carbon nanotube (CNT) FETs to build the sensors. The sensors could selectively measure potassium ions with a minimum detection limit of 1 nM. We utilized the sensor for the real-time monitoring of the potassium ion released from a live cell stimulated by nicotine. Notably, this method also allowed us to quantitatively monitor the cell responses by agonists and antagonists of nAChRs. These results suggest that our ion-selective CNT-FET sensor has potential uses in biological and medical researches such as the monitoring of ion-channel activity and the screening of drugs.

Nanoscale Mapping of Molecular Vibrational Modes via Vibrational Noise Spectroscopy.

We have developed a "vibrational noise spectroscopy (VNS)" method to identify and map vibrational modes of molecular wires on a solid substrate. In the method, electrical-noises generated in molecules on a conducting substrate were measured using a conducting atomic force microscopy (AFM) with a nanoresolution. We found that the bias voltage applied to the conducting AFM probe can stimulate specific vibrational modes of measured molecules, resulting in enhanced electrical noises. Thus, by analyzing noise-voltage spectra, we could identify various vibrational modes of the molecular wires on the substrates. Further, we could image the distribution of vibrational modes on molecule patterns on the substrates. In addition, we found that VNS imaging data could be further analyzed to quantitatively estimate the density of a specific vibrational mode in the layers of different molecular species. The VNS method allows one to measure molecular vibrational modes under ambient conditions with a nanoresolution, and thus it can be a powerful tool for nanoscale electronics and materials researches in general.

Fourier Transform Surface Plasmon Resonance of Nanodisks Embedded in Magnetic Nanorods.

In this study, we demonstrate the synthesis and application of magnetic plasmonic gyro-nanodisks (GNDs) for Fourier transform surface plasmon resonance based biodetection. Plasmonically active and magnetically responsive gyro-nanodisks were synthesized using electrochemical methods with anodized aluminum templates. Due to the unique properties of GNDs (magnetic responsiveness and surface plasmon bands), periodic extinction signals were generated under an external rotating magnetic field, which is, in turn, converted into frequency domains using Fourier transformation. After the binding of a target on GNDs, an increase in the shear force causes a shift in the frequency domain, which allows us to investigate biodetection for HA1 (the influenza virus). Most importantly, by modulating the number and the location of plasmonic nanodisks (a method for controlling the hydrodynamic forces by rationally designing the nanomaterial architecture), we achieved enhanced biodetection sensitivity. We expect that our results will contribute to improved sensing module performance, as well as a better understanding of dynamic nanoparticle systems, by harnessing the perturbed periodic fluctuation of surface plasmon bands under the modulated magnetic field.

Nanoscale "Noise-Source Switching" during the Optoelectronic Switching of Phase-Separated Polymer Nanocomposites.

A method is developed to directly map nanoscale "noise-source switching" phenomena during the optoelectronic switching of phase-separated polymer nanocomposites of tetrathiafulvalene (TTF) and phenyl-C61 -butyric acid methyl ester (PCBM) molecules dispersed in a polystyrene (PS) matrix. In the method, electrical current and noise maps of the nanocomposite film are recorded using a conducting nanoprobe, enabling the mapping of a conductivity and a noise-source density. The results provide evidence for a repeated modulation in noise sources, a "noise-source switching," in each stage of a switching cycle. Interestingly, when the nanocomposite is "set" by a high bias, insulating PS-rich phases shows a drastic decrease in a noise-source density which becomes lower than that of conducting TTF-PCBM-rich phases. This can be attributed to a trap filling by charge carriers generated from a TTF (donor)-PCBM (acceptor) complex. In addition, when the film is exposed to UV, an optical switching occurs due to chemical reactions which lead to irreversible changes on the noise-source density and conductivity. The method provides a new insight on noise-source activities during the optoelectronic switching of polymer nanocomposites and thus can be a powerful tool for basic noise research and applications in organic memory devices.

Mapping nanoscale effects of localized noise-source activities on photoconductive charge transports in polymer-blend films.

We develolped a method to directly image the nanoscale effects of localized noise-source activities on photoconducting charge transports in domain structures of phase-separated polymer-blend films of Poly(9,9-di-n-octylfluorenyl-2,7-diyl) and Poly(9,9-di-n-octylfluorene-alt-benzothiadiazole). For the imaging, current and noise maps of the polymer-blend were recorded using a conducting nanoprobe in contact with the surface, enabling the conductivity (σ) and noise-source density (N T) mappings under an external stimulus. The blend-films exhibited the phase-separation between the constituent polymers at domains level. Within a domain, high σ (low N T) and low σ (high N T) regions were observed, which could be associated with the ordered and disordered regions of a domain. In the N T maps, we observed that noise-sources strongly affected the conduction mechanism, resulting in a scaling behavior of σ âˆ [Formula: see text] in both ordered and disordered regions. When a blend film was under an influence of an external stimulus such as a high bias or an illumination, an increase in the σ was observed, but that also resulted in increases in the N T as a trade-off. Interestingly, the Δσ versus ΔN T plot exhibited an unusual scaling behavior of Δσ âˆ [Formula: see text] which is attributed to the de-trapping of carriers from deep traps by the external stimuli. In addition, we found that an external stimulus increased the conductivity at the interfaces without significantly increasing their N T, which can be the origin of the superior performances of polymer-blend based devices. These results provide valuable insight about the effects of noise-sources on nanoscale optoelectronic properties in polymer-blend films, which can be an important guideline for improving devices based on polymer-blend.

Nanoscale anomalous noise source switching with a trap-free current transition in a PEDOT:PSS film.

We imaged localized charge traps in a PEDOT:PSS film by using a scanning noise microscopy (SNM) system and observed anomalous noise source switching behaviors affecting the electrical characteristics of the film. The SNM system enabled us to measure the localized electrical current and noise maps of a PEDOT:PSS film with nanoscale resolution. The measured maps of the currents and noises were utilized to calculate effective charge trap densities in the film. As a result, we found non-homogeneous distributions of currents and effective charge trap densities on the localized area of the film due to the non-uniform distribution of PEDOT-rich and PSS-rich grains. At a low bias voltage, we observed high current levels and high charge trap densities in PEDOT-rich grains, while PSS-rich grains showed low-current levels and charge trap densities. Interestingly, the charge trap densities in both grains showed a noise source switching behavior with respect to the applied bias voltages, and the behavior strongly affected their electrical characteristic such as the trap-free transition of currents. These results indicate that the charge traps in a PEDOT:PSS film play an important role in the electrical characteristics of the films. Our observations provide a valuable insight on the understanding of the electrical characteristics of PEDOT:PSS films and an important guideline for its practical applications.

Mapping reversible photoswitching of molecular resistance fluctuations during the conformational transformation of azobenzene-terminated molecular switches.

We report a direct mapping and analysis of electrical noise in azobenzene-terminated molecular monolayers, revealing reversible photoswitching of the molecular resistance fluctuations in the layers. In this work, a conducting atomic force microscope combined with a homemade spectrum analyzer was used to image electrical current and noise at patterned self-assembled monolayers (SAMs) of azobenzene-terminated molecular wires on a gold substrate. We analyzed the current and noise imaging data to obtain maps of molecular resistances and amount of mean-square fluctuations in the resistances of the regions of trans-azobenzene and a cis/trans-azobenzene mixture. We revealed that the fluctuations in the molecular resistances in the SAMs were enhanced after the trans-to-cis isomerization, while the resistances were reduced. This result could be attributed to enhanced disorders in the molecular arrangements in the cis-SAMs. Furthermore, we observed that the changes in the resistance fluctuations were reversible with respect to repeated trans-to-cis and cis-to-trans isomerizations, indicating that the effects originated from reversible photoswitching of the molecular structures rather than irreversible damages of the molecules. These findings provide valuable insights into the electrical fluctuations in photoswitchable molecules, which could be utilized in further studies on molecular switches and molecular electronics in general.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity.

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

High-Speed Lateral Flow Strategy for a Fast Biosensing with an Improved Selectivity and Binding Affinity.

We report a high-speed lateral flow strategy for a fast biosensing with an improved selectivity and binding affinity even under harsh conditions. In this strategy, biosensors were fixed at a location away from the center of a round shape disk, and the disk was rotated to create the lateral flow of a target solution on the biosensors during the sensing measurements. Experimental results using the strategy showed high reaction speeds, high binding affinity, and low nonspecific adsorptions of target molecules to biosensors. Furthermore, binding affinity between target molecules and sensing molecules was enhanced even in harsh conditions such as low pH and low ionic strength conditions. These results show that the strategy can improve the performance of conventional biosensors by generating high-speed lateral flows on a biosensor surface. Therefore, our strategy can be utilized as a simple but powerful tool for versatile bio and medical applications.

Fourier Transform Surface Plasmon Resonance (FTSPR) with Gyromagnetic Plasmonic Nanorods.

An unprecedented active and dynamic sensing platform based on a LSPR configuration that is modulated by using an external magnetic field is reported. Electrochemically synthesized Au/Fe/Au nanorods exhibited plasmonically active behavior through plasmonic coupling, and the middle ferromagnetic Fe block responded to a magnetic impetus, allowing the nanorods to be modulated. The shear force variation induced by the specific binding events between antigens and antibodies on the nanorod surface is used to enhance the sensitivity of detection of antigens in the plasmonics-based sensor application. As a proof-of-concept, influenza A virus (HA1) was used as a target protein. The limit of detection was enhanced by two orders of magnitude compared to that of traditional LSPR sensing.

Bioelectronic Nose Using Odorant Binding Protein-Derived Peptide and Carbon Nanotube Field-Effect Transistor for the Assessment of Salmonella Contamination in Food.

Salmonella infection is the one of the major causes of food borne illnesses including fever, abdominal pain, diarrhea, and nausea. Thus, early detection of Salmonella contamination is important for our healthy life. Conventional detection methods for the food contamination have limitations in sensitivity and rapidity; thus, the early detection has been difficult. Herein, we developed a bioelectronic nose using a carbon nanotube (CNT) field-effect transistor (FET) functionalized with Drosophila odorant binding protein (OBP)-derived peptide for easy and rapid detection of Salmonella contamination in ham. 3-Methyl-1-butanol is known as a specific volatile organic compound, generated from the ham contaminated with Salmonella. We designed and synthesized the peptide based on the sequence of the Drosophila OBP, LUSH, which specifically binds to alcohols. The C-terminus of the synthetic peptide was modified with three phenylalanine residues and directly immobilized onto CNT channels using the π-π interaction. The p-type properties of FET were clearly maintained after the functionalization using the peptide. The biosensor detected 1 fM of 3-methyl-1-butanol with high selectivity and successfully assessed Salmonella contamination in ham. These results indicate that the bioelectronic nose can be used for the rapid detection of Salmonella contamination in food.

Magnetically-refreshable receptor platform structures for reusable nano-biosensor chips.

We developed a magnetically-refreshable receptor platform structure which can be integrated with quite versatile nano-biosensor structures to build reusable nano-biosensor chips. This structure allows one to easily remove used receptor molecules from a biosensor surface and reuse the biosensor for repeated sensing operations. Using this structure, we demonstrated reusable immunofluorescence biosensors. Significantly, since our method allows one to place receptor molecules very close to a nano-biosensor surface, it can be utilized to build reusable carbon nanotube transistor-based biosensors which require receptor molecules within a Debye length from the sensor surface. Furthermore, we also show that a single sensor chip can be utilized to detect two different target molecules simply by replacing receptor molecules using our method. Since this method does not rely on any chemical reaction to refresh sensor chips, it can be utilized for versatile biosensor structures and virtually-general receptor molecular species.

Carbon and metal nanotube hybrid structures on graphene as efficient electron field emitters.

We report a facile and efficient method for the fabrication of highly-flexible field emission devices by forming tubular hybrid structures based on carbon nanotubes (CNTs) and nickel nanotubes (Ni NTs) on graphene-based flexible substrates. By employing an infiltration process in anodic alumina oxide (AAO) templates followed by Ni electrodeposition, we could fabricate CNT-wrapped Ni NT/graphene hybrid structures. During the electrodeposition process, the CNTs served as Ni nucleation sites, resulting in a large-area array of high aspect-ratio field emitters composed of CNT-wrapped Ni NT hybrid structures. As a proof of concepts, we demonstrate that high-quality flexible field emission devices can be simply fabricated using our method. Remarkably, our proto-type field emission devices exhibited a current density higher by two orders of magnitude compared to other devices fabricated by previous methods, while maintaining its structural integrity in various bending deformations. This novel fabrication strategy can be utilized in various applications such as optoelectronic devices, sensors and energy storage devices.

A Vanadium Dioxide Metamaterial Disengaged from Insulator-to-Metal Transition.

We report that vanadium dioxide films patterned with λ/100000 nanogaps exhibit an anomalous transition behavior at millimeter wavelengths. Most of the hybrid structure's switching actions occur well below the insulator to metal transition temperature, starting from 25 °C, so that the hysteresis curves completely separate themselves from their bare film counterparts. It is found that thermally excited intrinsic carriers are responsible for this behavior by introducing enough loss in the context of the radically modified electromagnetic environment in the vicinity of the nanogaps. This phenomenon newly extends the versatility of insulator to metal transition devices to encompass their semiconductor properties.

Observation of localized strains on vertically grown single-walled carbon nanotube forests via polarized Raman spectroscopy.

Vertically grown single-walled carbon nanotube (V-SWCNT) forests, synthesized by water-assisted plasma-enhanced chemical vapor deposition, were studied using polarized micro-Raman spectroscopy. Among three different sections (root, center and end) along the vertical growth direction, the degree of V-SWCNT alignment was highest in the center section. Raman frequency red-shifts up to 7 and 13 cm(-1), for RBM and G-band, respectively, were observed in the center section, with respect to the Raman frequencies measured in the root and the end sections. Raman frequency downshift and concurrent linewidth broadening of the G-band, revealing a localized strain, were also observed in the center section. The existence of a localized strain in the center section of the V-SWCNT was further confirmed by observing a strong polarization anisotropy of up to 8 cm(-1) in the G-band Raman frequency for different polarized Raman scattering configurations at the same probed spot.

Gate-bias stress-dependent photoconductive characteristics of multi-layer MoS2 field-effect transistors.

We investigated the photoconductive characteristics of molybdenum disulfide (MoS2) field-effect transistors (FETs) that were fabricated with mechanically exfoliated multi-layer MoS2 flakes. Upon exposure to UV light, we observed an increase in the MoS2 FET current because of electron-hole pair generation. The MoS2 FET current decayed after the UV light was turned off. The current decay processes were fitted using exponential functions with different decay characteristics. Specifically, a fast decay was used at the early stages immediately after turning off the light to account for the exciton relaxation, and a slow decay was used at later stages long after turning off the light due to charge trapping at the oxygen-related defect sites on the MoS2 surface. This photocurrent decay phenomenon of the MoS2 FET was influenced by the measurement environment (i.e., vacuum or oxygen environment) and the electrical gate-bias stress conditions (positive or negative gate biases). The results of this study will enhance the understanding of the influence of environmental and measurement conditions on the optical and electrical properties of MoS2 FETs.

Highly Sensitive Real-Time Monitoring of Adenosine Receptor Activities in Nonsmall Cell Lung Cancer Cells Using Carbon Nanotube Field-Effect Transistors.

Adenosine metabolism through adenosine receptors plays a critical role in lung cancer biology. Although recent studies showed the potential of targeting adenosine receptors as drug targets for lung cancer treatment, conventional methods for investigating receptor activities often suffer from various drawbacks, including low sensitivity and slow analysis speed. In this study, adenosine receptor activities in nonsmall cell lung cancer (NSCLC) cells were monitored in real time with high sensitivity through a carbon nanotube field-effect transistor (CNT-FET). In this method, we hybridized a CNT-FET with NSCLC cells expressing A2A and A2B adenosine receptors to construct a hybrid platform. This platform could detect adenosine, an endogenous ligand of adenosine receptors, down to 1 fM in real time and sensitively discriminate adenosine among other nucleosides. Furthermore, we could also utilize the platform to detect adenosine in complicated environments, such as human serum. Notably, our hybrid platform allowed us to monitor pharmacological effects between adenosine and other drugs, including dipyridamole and theophylline, even in human serum samples. These results indicate that the NSCLC cell-hybridized CNT-FET can be a practical tool for biomedical applications, such as the evaluation and screening of drug-candidate substances.

Duffy Antigen Receptor for Chemokines (DARC) Nanodisc-Based Biosensor for Detection of Staphylococcal Bicomponent Pore-Forming Leukocidins.

Staphylococcus aureus (S. aureus) is an opportunistic infectious pathogen, which causes a high mortality rate during bloodstream infections. The early detection of virulent strains in patients' blood samples is of medical interest for rapid diagnosis. The main virulent factors identified in patient isolates include leukocidins that bind to specific membrane receptors and lyse immune cells and erythrocytes. Duffy antigen receptor for chemokines (DARC) on the surface of specific cells is a main target of leukocidins such as gamma-hemolysin AB (HlgAB) and leukocidin ED (LukED). Among them, HlgAB is a conserved and critical leukocidin that binds to DARC and forms pores on the cell membranes, leading to cell lysis. Current methods are based on ELISA or bacterial culture, which takes hours to days. For detecting HlgAB with faster response and higher sensitivity, we developed a biosensor that combines single-walled carbon nanotube field effect transistors (swCNT-FETs) with immobilized DARC receptors as biosensing elements. DARC was purified from a bacterial expression system and successfully reconstituted into nanodiscs that preserve binding capability for HlgAB. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) showed an increase of the DARC-containing nanodisc size in the presence of HlgAB, indicating the formation of HlgAB prepore or pore complexes. We demonstrate that this sensor can specifically detect the leukocidins HlgA and HlgAB in a quantitative manner within the dynamic range of 1 fM to 100 pM with an LOD of 0.122 fM and an LOQ of 0.441 fM. The sensor was challenged with human serum spiked with HlgAB as simulated clinical samples. After dilution for decreasing nonspecific binding, it selectively detected the toxin with a similar detection range and apparent dissociation constant as in the buffer. This biosensor was demonstrated with remarkable sensitivity to detect HlgAB rapidly and has the potential as a tool for fundamental research and clinical applications, although this sensor cannot differentiate between HlgAB and LukED as both have the same receptor.