Recent statistics show that the incidence and mortality of cancer are on the rise. Among all types of cancer, lung cancer and liver cancer are the most prevalent. We have many biomarkers for these two cancers, among which the cytokeratin fragment 21-1 (CYFRA 21-1) and α-fetoprotein (AFP) are the most common and widely used. Among the various detection methods, the field effect transistor (FET) biosensor is one of the most attractive approaches, providing a label-free, fast, and low-cost electrical detection of biomarkers with high specificity and sensitivity. In previous work, we applied biomarkers for a single cancer type. With the detection of CYFRA 21-1 and neuron-specific enolase (NSE), lung cancer was differentiated in the early stages. Compared with the early work, the biomarkers for the two cancer types, CYFRA 21-1 for lung cancer and AFP for liver cancer, were prepared in this work. The detection of CYFRA 21-1 and AFP in human serum was achieved at the same time with the limits of detection of 1 and 10 ng mL−1, while the cut-off values were 4 and 10 ng mL−1. The method featured short analytical time, small sample volume, and low cost. With its good selectivity and appropriate sensitivity, clinical application will become popular in the future.

In recent years, food safety concerning food allergy has received increasing attention globally. A simple and sensitive detection method should be developed to measure trace amounts of allergens in foods. Here, we propose a label-free field effect transistor (FET)-based biosensing system for the detection of a buckwheat allergenic protein, BWp16, by surfactant-induced signal amplification. BWp16 could be detected by coupling with an anionic surfactant, sodium dodecyl sulfate (SDS), as this coupling enhanced the net charge of the protein, enough to be detected by FET biosensors. A significant response was observed when the allergen was coupled with SDS, while the responses were decreased or unchanged when it was coupled with a cationic or non-ionic surfactant, suggesting that the SDS coupling maintains the antibody recognition ability of the target allergen, and it would be useful to enhance the sensor responses. The fluorescence spectroscopic measurement revealed that the SDS molecules were successfully coupled with target allergenic protein BWp16, resulting in an increase in its net charge. Furthermore, we demonstrated that the FET biosensor enables specific detection of the allergen in food at the desired concentration levels for food safety analysis, suggesting that it could be used as an alternative food allergen analyzer, both industrially and domestically. (C) 2017 The Authors. Published by Elsevier B.V.

With the objective of finding an avenue for development of magnetic hyperthermia as an effective mesothelioma treatment, the influence of heating by magnetite nanoparticles (MNPs) with a diameter of similar to 40 nm, which were incorporated into cells and then subjected to AC magnetic field, on induction of cell death was investigated in all three histological subtypes of human mesothelioma cells (i.e., epithelioid NCI-H28, sarcomatoid NCI-H2052, and biphasic MSTO-211H cells). Cellular uptake of MNPs was observed in all cell types, but the amount of MNPs incorporated per cell into MSTO-211H cells was smaller than in NCI-H28 and NCI-H2052 cells. On the other hand, cell death induced by cellular uptake of MNPs was observed specifically in MSTO-211H cells. Hence, when cells are heated by intracellular MNPs under AC magnetic field, a high degree of cell mortality in NCI-H28 and NCI-H2052 cells is induced by the temperature increase derived from the high amount of intracellular MNPs, but the combination of intracellular heating and cell-type-specific toxicity of MNPs induced high rates of cell death in MSTO-211H cells even at a lower temperature. Almost all of the heated cells were dead after 24-h incubation at 37 degrees C in all histological subtypes. Additionally, higher mortalities were observed in all three types of mesothelioma cells after MNPs-heating, as compared to the heating with a thermostatic bath. Herein, the significance of cellular uptake of MNPs for effectively inducing cell death in mesothelioma has been demonstrated in vitro. (C) 2017 Elsevier B.V. All rights reserved.

The concept of unobtrusive physiological balance sensing system implementing biosensors is discussed. Biosensors connected with a data system are expected to play a significant role when we extend the sensing objects from body to mind and spirit. Here, we describe the unobtrusive monitoring system using field effect transistor-type sensors and wireless communication devices. Substances subject to the survey of our research will include small ions, immunoglobulins, and hormones. (C) 2017 Wiley Periodicals, Inc.

To evaluate the efficiency with which intra-and extracellular magnetite nanoparticles (MNPs) induce cell death under an alternating magnetic field (AMF), we comparatively investigated two systems consisting of MCF-7 human breast cancer cells and MNPs: one is a "simply-added" system, which is essentially a simple mixture of cells and extracellular MNPs, and the other is a "pre-cultivated" system that contains both intra-and extracellular MNPs. We also evaluated the effect of heating by thermostatic water bath (WB) on cell death in both systems. The degree of cell death was greater under heating with MNPs subjected to AMF than in the WB-heating in both systems. At higher doses of MNPs, the degree of cell death was greater in the "pre-cultivated" system than in the "simply-added" system using both heating methods. The cellular uptake of MNPs induced slight cell damage and caused a high degree of cell death at higher temperatures. A significant decrease in cell viability was observed in the presence of internalized MNPs under the AMF and was suggested to be a result of the combined effect of intracellular heating and cellular damage by MNPs.

Theoretical analyses of L-alanine (L-Ala)- and L-homocysteine (L-Hcy)-Cu(II) complexes in basic, neutral, and acidic solutions were carried out using density functional theory to investigate the pH dependence of the formation mechanism of amino acid-Cu(II) complexes. The calculated complex formation energies indicate that the amino acid-Cu(II) complexes were expected to form in basic and neutral solutions but not in acidic solutions. The factors that determine the stability of these complexes are the coordination ability of each amino acid and the significance of intramolecular interactions among ligands within the complexes. As predicted from the molecular structure, in neutral solutions, the coordination ability of amino acid becomes lower than that in basic solutions because of the inert structure of the protonated amino group, -NH3+; however, the coordination ability originating from the -COO- group is estimated to be sufficient for stabilizing the entire complex system. Moreover, two H2O molecules coordinate with the central Cu2+ ion from the equatorial direction and interact with the coordinating amino acids, providing additional stability within the complex. In contrast, in acidic solutions, the complex does not have either sufficient coordination ability of amino acids or effective intramolecular interactions within the complex.

A robust and applicable strategy of signal amplification for field effect transistor (FET) biosensor is of scientifically and technologically importance to detect wide range of target molecules, particularly for the molecules of low charge density, and to configure highly sensitive analysis. In this communication, we demonstrate a simple technique to modify the net charge of target protein based on the concept of protein conjugation for the detection of prion, which is infectious and transmissible protein in neurodegenerative disorders. The increases of prion net charge after chemical modification generate signal amplification and have remarkably enhanced the sensitivity of FET biosensor below than femtomolar (fM) level. Thus, we suggest that such strategy is promising technique for achieving a highly sensitive detection at very low concentration that is useful for early determination of protein biomarkers. (C) 2016 Elsevier B.V. All rights reserved.

Food allergens, especially buckwheat proteins, sometimes induce anaphylactic shock in patients after ingestion. Development of a simple and rapid screening method based on a field effect transistor (FET) biosensor for food allergens in food facilities or products is in demand. In this study, we achieved the FET detection of a buckwheat allergenic protein (BWp16), which is not charged enough to be electrically detected by FET biosensors, by introducing additional negative charges from anionic surfactants to the target proteins. A change in the FET characteristics reflecting surface potential caused by the adsorption of target charged proteins was observed when the target sample was coupled with the anionic surfactant (sodium dodecyl sulfate
SDS), while no significant response was detected without any surfactant treatment. It was suggested that the surfactant conjugated with the protein could be useful for the charge amplification of the target proteins. The surface plasmon resonance analysis revealed that the SDS-coupled proteins were successfully captured by the receptors immobilized on the sensing surface. Additionally, we obtained the FET responses at various concentrations of BWp16 ranging from 1 ng/mL to 10 μg/mL. These results suggest that a signal amplification method for FET biosensing is useful for allergen detection in the food industry.

The concept of unobtrusive physiological balance sensing system implementing biosensors is discussed. Biosensors connected with a data system is expected to play a significant role when we extend the sensing objects from body to mind and spirit. Here, we describe the unobtrusive monitoring system using FET-type sensors and wireless communication devices. Substances subject to the survey of our research will include small ions, immunoglobulins, and hormones.

To compare heat generation under an AC magnetic field for inducing cancer cell death, CoFe2O4 and Fe3O4 nanoparticles with a diameter of similar to 10 nm were synthesized by hydrolysis in an aqueous solution containing the metal chlorides iron(III) chloride and cobalt(II) or iron(II) chloride, with spermine or N,N'-bis(3-aminopropyl)butane-1,4-diamine, as a base and a protective reagent. Both CoFe2O4 and Fe3O4 nanoparticles were incorporated into human breast cancer MCF-7 cells; the nanoparticles exhibited little toxicity on the cells. When the cells containing nanoparticles were subjected to an AC magnetic field, MCF-7 cell death was induced by heat generated from similar to 10-nm CoFe2O4 nanoparticles but not from similar to 10-nm Fe3O4 nanoparticles. An increase in coercivity derived from the substitution of Fe2+ with Co2+ facilitated the ability of the nanoparticles to induce cell death in human breast cancer cells under an AC magnetic field. (C) 2015 Elsevier Ltd. All rights reserved.

Nanoparticle uptake and cell death following addition of magnetite nanoparticles (MNPs) with a diameter of similar to 10 nm were evaluated in three histological types of human mesothelioma cells, NCI-H28 (epithelioid), NCI-H2052 (sarcomatoid), and MSTO-211H (biphasic) cells, and human breast cancer MCF-7 cells. Dose dependent cell death was observed in MSTO-211H cells but not in MCF-7 cells, although cellular uptake of MNPs was observed in both cell types. Mesothelioma NCI-H28 and NCI-H2052 cells showed behavior more similar to that of breast cancer MCF-7 cells than that of mesothelioma MSTO-211H cells. DNA fragmentation and microarray analyses suggested that MNPs induced transforming growth factor beta 2 related apoptosis in MSTO-211H cells. On the other hand, the viability of human mesothelioma cells containing MNPs with a diameter of similar to 40 nm was investigated after exposure to an alternating magnetic field. Temperature increase under the alternating magnetic field and high rates of cell death were observed in all three histological types of human mesothelioma.

Detection of tumor markers is important for cancer diagnosis. Field effect transistor (FET) has been recognized as a powerful technique for label-free, sensitive, real-time, and multifunctional biosensing. Here, we developed FET biosensors that allow the label-free detection of cytokeratin fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE), useful tumor markers for lung cancer type differentiation. It was found that the FET biosensor was capable of quantitatively detecting these tumor markers in both phosphate-buffered saline and human serum. Additionally, we developed a multianalyte FET biosensor for the selective multiplexed detection of CYFRA 21-1 and NSE at the same time, by integrating two antibody types on the same chip, providing a step towards the realization of sensor arrays. The multianalyte FET biosensor, as described herein, will help for lung cancer differential diagnosis with advantages of simple and rapid detection procedures, low sample consumption, and low cost. (C) 2015 Elsevier B.V. All rights reserved.

Simple and accurate detection of prion proteins in biological samples is of utmost importance in recent years. In this study, we developed a label-free electrical detection-based field effect transistor (FET) biosensor using thiamine as a probe molecule for a non-invasive and specific test of human prion protein detection. We found that thiamine-immobilized FETs can be used to observe the prion protein oligomer, and might be a significant test for the early diagnosis of prion-related diseases. The thiamine-immobilized FET was also demonstrated for the detection of prion proteins in blood serum without any complex pre-treatments. Furthermore, we designed a dual-ligand binding approach by the addition of metal ions as a second ligand to bind with the adsorbed prion protein on the thiamine-immobilized surface. When the prion attached to metal ions, the additional positive charge was induced on the gate surface of the FET. This approach was capable of amplifying the magnitude of the FET response and of enhancing the sensitivity of the FET biosensor. Detection of prion proteins has achieved the required concentration for clinical diagnosis in blood serum, which is less than 2 nM. In summary, this FET biosensor was successfully applied to prion detection and proved useful as a simple, fast, sensitive and low-cost method towards a mass-scale and routine blood screening-based test. (C) 2014 Elsevier B.V. All rights reserved.

We have developed a field effect transistor (FET) sensor to sensitively detect copper ions (Cu2+) in a human serum (HS) sample for promising health-care diagnosis. By utilizing a Cu2+-binding prion protein that was immobilized on the FET gate surface, such an FET sensor can provide a simple, label free and highly selective performance, even in HS samples. We demonstrated the sensitivity of the sensor at the nanomolar level, 0-100 nM, which is very useful for the detection range of Cu2+ deficiency in practical applications.

In this paper, we report the effects of chemical treatment of indium tin oxide (ITO) surface on its surface chemistry such as chemical composition and surface roughness and on its usage as an electrode with monolayer modification. Atomic force microscopy, angel-resolved X-ray photoelectron spectroscopy, and Kelvin probe force microscopy have been used to investigate the morphology and the chemical properties of commercial thin ITO films after several treatments commonly used prior to the formation of organic layer on the surface. The amount of spike present on the surface of as-received ITO substrates was significantly reduced by etching with KOH whereas the roughness of ITO increased with HCI etching. We demonstrated that the successive treatment of ITO electrode with HCI and KOH affects the surface characteristics such as roughness and work function, contributing to the potentiometric detection of tiyptophan. (C) 2014 Elsevier B.V. All rights reserved.

Detection of tumor markers is important for cancer diagnosis. Field-effect transistors (FETs) are a promising method for the label-free detection of trace amounts of biomolecules. However, detection of electrically charged proteins using antibody-immobilized FETs is limited by ionic screening by the large probe molecules adsorbed to the transistor gate surface, reducing sensor responsiveness. Here, we investigated the effect of probe molecule size on the detection of a tumor marker, alpha-fetoprotein (AFP) using a FET biosensor. We demonstrated that the small receptor antigen binding fragment (Fab), immobilized on a sensing surface as small as 2-3 nm, offers a higher degree of sensitivity and a wider concentration range (100 pg/mL-1 mu g/mL) for the FET detection of AFP in buffer solution, compared to the whole antibody. Therefore, the use of a small Fab probe molecule instead of a whole antibody is shown to be effective for improving the sensitivity of AFP detection in FET biosensors. Furthermore, we also demonstrated that a Fab-immobilized FET subjected to a blocking treatment, to avoid non-specific interactions, could sensitively and selectively detect AFP in human serum.

We fabricated dye-sensitized solar cells (DSSCs) with synthetic quartz nanoparticle (SQNP)-supported Pt/fluorine doped tin oxide counter electrodes to utilize an adsorptive capacity of synthetic quartz. The amperage of I-3(-) reduction was 1.6 times higher with SQNP than that without SQNP. SQNP also improved the photocurrent density-voltage characteristics and the incident photon to current conversion efficiency spectra in the visible region. These suggest that SQNP enhances the I-3(-) reduction activity on the counter electrode and the electron transfer to the photoanode. The SQNP-supported counter electrode is expected to be useful to raise the efficiency of a DSSC. (C) The Electrochemical Society of Japan, All rights reserved.

We propose, as an alternative to conventional spectroscopic assays, a simple method for discriminating fibrous amyloid proteins by using a label-free semiconductor-based biosensor. The highly sensitive assay is expected to be useful for accelerating amyloid related research.

Influenza virus, through cell invasion and propagation with the interaction between hemagglutinin (HA) present on its surface and glycans on the host cell, causes a rapidly spreading infection throughout the world. In the present investigation, we succeeded for the first time in the attomolar-level sensing and discrimination of influenza A viral HA molecules H1 and H5 by using a glycan-immobilized field effect transistor (FET) biosensor. The small ligand glycans immobilized on the FET device, which make effective use of the charge-detectable region for FET-based detection in terms of Debye length, gave an advantage in the highly sensitive detection of the proteins. Two kinds of trisaccharides receptors terminating in sialic acid-alpha 2,6-galactose (6'-sialyllactose) and in sialic acid-alpha 2,3-galactose (3'-sialyllactose) were conjugated directly with the SiO2 surface of FET devices by a simple glycoblotting method using the self-assembled monolayer (SAM) of aminooxy terminated silane-coupling reagent, 3-aminooxypropyltriethoxysilane. Furthermore, it was demonstrated that the FETs with densely immobilized glycans, which possess the high capture ability by achieving the glycoside cluster effect, clearly distinguish HA molecules between their subtypes H1 (human) and H5 (avian) at the attomolar level, while the conventional method based on HA antibodies achieves only picomolar-level detection. Our findings indicate that the glycan-immobilized FET is a promising device to detect various pathogenic bacteria and viruses through glycan-protein interaction found ubiquitously in many infectious diseases.

Magnetite nanoparticles are expected to be applied in the medical field because of their biocompatibility and high saturated magnetization. In this paper, magnetite nanoparticles with a diameter of approximately 40 nm were evaluated for their safety by using mouse embryonic stein (mES) cells. First, various doses of magnetite nanoparticles were added to mES cells to find an optimal dose and to evaluate viability and keeping undifferentiated states of mES. The uptake of nanoparticles by mES cells was confirmed by using cytospin and transmission electron microscopy. Next, mES cells containing magnetite nanoparticles were collected by a magnet column 24 h after the addition of magnetite nanoparticles, and the change in the ratio of those mES cells to the total mES cells was assayed by FACS 0, 4, 8, 12, 16, 24, 48 and 72 h after incubation. The result showed that the ratio decreased with time, indicating that the mES cells excreted the nanoparticles, for there was no change in the total number of cells. Based on these results, it was concluded that magnetite nanoparticles were safe to mES cells. (c) 2012 Elsevier B.V. All rights reserved.

Matrix metalloproteinase (MMP) is known to be involved in chronic inflammation, tumor invasion, and carcinogenesis. To detect MMP-2, we examined the use of field effect transistors (FETs). After the addition of MMP-2 to a fibronectin (FN)-immobilized gate, negative value of FET response was observed, which indicates MMP-2 decreased the amount of negative charges arising from FN molecules. This FET device successfully detected MMP-2 by utilizing degradation of FN on the gate.

Superparamagnetic and ferromagnetic magnetite nanoparticles, with diameters of approximately 13 and 44 nm, respectively, were synthesized and their uptake amount and heating efficiency were evaluated for application to magnetic hyperthermia. Both nanoparticles had almost the same zeta-potential (+10.2 mV) and hydrodynamic size (similar to 1 mu m) and there was no significant difference in their uptake amount 18 h after they were added to the medium. After internalization, the ferromagnetic nanoparticles incorporated in human breast cancer cells (MCF-7) showed a higher heating efficiency than the superparamagnetic nanoparticles when an external magnetic field (4 kW, 250 kHz) high enough to produce heat by hysteresis loss was applied, followed by cellular death of MCF-7 with high ferromagnetic nanoparticle content. (C) 2012 Elsevier B.V. All rights reserved.

A self-assembled monolayer (SAM) of L-homocysteine (L-Hcy) formed on the surface of a gold-deposited gate of a field effect transistor (FET) was used to differentiate between enantiomers of amino acids, for which the formation of diastereomeric metal complexes is fundamental for chiral discrimination. Here, we focus our attention on the dependence of the FET response on the analyte amino acids, the central metal ions involved in complex formation, and the solution pH. Using the L-Hcy SAM-modified gate with added Cu(II), notable negative FET responses were enantioselectively observed for the L-enantiomers of alanine (Ala), phenylalanine, and tryptophan, whereas differences in the FET responses between enantiomers were negligible for asparagine and aspartic acid. Regarding the enantioselectivity for Ala, the addition of Cu(II) was demonstrated to show higher selectivity as compared to other metal ions such as Co(II) and Ni(II). Moreover, for the addition of L-Ala and Cu(II), a particularly strong negative FET response was observed at pH 5.5. (C) 2011 Elsevier Ltd. All rights reserved.

The effect of surface modification of indium tin oxide (ITO) electrode on its potential response to tryptophan was investigated for ITO substrates with different surface roughness. It was found that a small difference in surface roughness, between similar to 1 and similar to 2 nm of R(a) evaluated by atomic force microscopy, affects the rest potential of ITO electrode in the electrolyte. A slight difference in In:Sn ratio at the near surface of the ITO substrates, measured by angle-resolved X-ray photoelectron spectrometry and Auger electron spectroscopy is remarkable, and considered to relate with surface roughness. Interestingly, successive modification of the ITO surface with aminopropylsilane and disuccinimidyl suberate, of which essentiality to the potential response to indole compounds we previously reported, improved the stability of the rest potential and enabled the electrodes to respond to tryptophan in case of specimens with R(a) values ranging between similar to 2 and similar to 3 nm but not for those with R(a) of similar to 1 nm. It was suggested that there are optimum values of effective work function of ITO for specific potential response to tryptophan, which can be obtained by the successive modification of ITO surface. (C) 2011 Elsevier Ltd. All rights reserved.

A novel potentiometric method using an indium tin oxide (ITO) electrode, surface-treated with aminopropylsilane and disuccinimidyl suberate successively, has been developed for measuring serotonin (5-HT), 5-hydroxy-L-tryptophan (5-HTP), 5-hydroxy-indole-acetic acid (5-HIAA), and melatonin (MT) (N-acetyl-5-methoxytryptamine) in phosphate buffered saline (PBS) solution (pH 7.4). A linear concentration range of 1 nM to 100 mu M was obtained with a correlation coefficient of 0.995 for all target analytes. The minimum detectable concentration obtained was 0.1 nM for 5-HT and 1.0 nM for other analytes. The relationship between the molecular structure of the indole derivatives and the enhanced potential shift behaviour was also discussed. This simple and efficient method can be used to measure other neurotransmitters, as well.

The application of field effect transistor (FET) to chiral discrimination was investigated. An Au film vapor-deposited on a self-assembled monolayer (SAM) of (3-mercaptopropyl)trimethoxysilane, which was formed on the SiO(2) gate of FET as an adhesive and insulating layer, stabilizes the drain current-gate voltage (I(d)-V(g)) property of FET. The modification by homocysteine(Hcy)SAM on the surface of Au-coated gate makes it possible for the FET to distinguish between the enantiomers of alanine (Ala). Namely, after the sequential addition of Ala and Cu(II) to a K(2)SO(4) solution in this system, it was confirmed that the lateral shift of I(d)-V(g) curves for the FET corresponded to the chirality of Ala. With the L-Hcy SAM-modified gate, a notable negative shift was observed for L-Ala, whereas the shift observed with D-Ala was much smaller. In contrast, opposite results were obtained with D-Hcy SAM. Results of quartz crystal microbalance measurement suggested that such an FET response was originated from the enantioselective formation of diastereomeric Cu complexes with Ala molecules on the Hey SAM. This system was demonstrated to respond quantitatively to one enantiomeric form of Ala in mixed solutions of two enantiomers as well as in pure enantiomeric solutions (C) 2010 Elsevier Ltd. All rights reserved.

Potential response of indium tin oxide (ITO) electrode modified by treatment with disuccinimidyl suberate (DSS) was investigated to various target molecules. Distinctively, the DSS-modified ITO electrode exhibited a potential shift to the molecules possessing an indole group such as tryptophan, tryptamine and indole propionic acid, while little response to benzoic acid, phenylalanine, proline, proline amide, and arginine was observed. In addition, the combination of this specificity to indoles and enantioselective affinity of human serum albumin (HSA), which was additionally immobilized on the DSS-modified ITO electrode, brought about enantioselective potential response to tryptophan.

This paper describes an overview of our research with the title of Establishment of Electrochemical Device Engineering. The goal of this work is to develop systematic methodologies for the creation of advanced materials and devices based on the design of the interface, which is derived from our study of the practical application of Electrochemical Nanotechnology. We introduce three-, two-, and zero-dimensional viewpoints to the design of the interface between electrode and electrolyte based on electrochemical nanotechnology. In this manuscript, two-dimensional design is explained first and then three- and zero-dimensional topics are mentioned.

Internalization of magnetite nanoparticles with diameter of approximately 40 turn into normal and cancer cells was examined by microscopic observation and flow cytometry. Magnetite nanoparticles were synthesized by hydrolysis in an aqueous solution containing ferrous chloride with organic amines as a base. It was demonstrated that the difference in surface charge of magnetite nanoparticles brought about the difference in uptake efficiency. The nanoparticles with positive charge showed higher internalization into human breast cancer cells than the nanoparticles with negative charge, while the degree of internalization of the positively- and negatively-charged nanoparticles into human umbilical vein endothelial cells (HUVEC) was almost the same. (C) 2009 Elsevier B.V. All rights reserved.

The application of localized surface plasmon resonance (LSPR) of gold nanoparticles for the detection of biotin-streptavidin binding, as a typical biological reaction, was investigated by using optical waveguide spectroscopy, and two different modes for the use of gold nanoparticles, one as a probe and the other as a label were compared with each other. The combination with optical waveguide spectroscopy was found to bring about a high sensitivity for the biomolecular detection system using LSPR of gold nanoparticles in both modes. In particular, the mode using gold nanoparticles as a label was demonstrated to be of advantage to devising proper procedures for using nanoparticles and evaluating actual response relevant to the phenomenon concerned, and thus to sensitive detection. (C) 2009 Elsevier Inc. All rights reserved.

The use of Tb3+ as a center ion and media to introduce more exogenously negative charges onto double-stranded DNA (dsDNA), can greatly enhance potentiometric signals produced by the shift of gate voltage of field effect transisitor (FET). Furthermore, different affinities of Tb3+ to normal and mismatched dsDNAs amplified the signal difference between their detections, which can improve the discrimination of single nucleotide polymorphism.

A facile and simple approach has been described for the synthesis of magnetite nanoparticles and iron oxyhydroxide nanorods using biogenic polyamines. At room temperature, highly crystalline magnetite particles with average size of 44 ± 2 and 37 ± 1 nm were synthesized with spermine and spermidine, respectively. The formation of nanoparticles was characterized with TEM, HRTEM, XPS and SQUID. The magnetite nanoparticles formed by the biogenic polyamines exhibits ferrimagnetic behavior at 300 K. When the reaction was carried out at low temperature, high aspect ratio, well crystalline nanorods were observed. X-ray diffraction and Infrared spectroscopy suggests that the nanorods correspond to lepidocrocite (γ-FeOOH). TEM analysis shows each bundle consisting of several nanorods stacked together by side on fashion. γ-FeOOH nanorods with high aspect ratio of 70 were observed. The SQUID analysis reveals that the lepidocrocite nanorods exhibit superparamagnetic behavior at room temperature. ©The Electrochemical Society.

A facile and simple approach for the synthesis of nanosized iron oxide and oxyhydroxide using biogenic polyamines is described. At room temperature, the highly crystalline nanoparticles of magnetite (Fe(3)O(4)) with average sizes of 44 +/- 2 and 37 +/- 1 nm were synthesized with spermine and spermidine, respectively. The magnetite nanoparticles formed by the biogenic polyamines exhibited a ferrimagnetic behavior at room temperature. When the same reaction was carried out at low temperature, crystalline nanorods of lepidocrocite (gamma-FeOOH) with a high aspect ratio were formed. It was revealed that the lepidocrocite nanorods with an aspect ratio of 70 formed bundles, each of which consisted of several nanorods stacked together by the side on fashion. It was suggested that the nanorods are of single-crystalline nature and exhibit a superparamagnetic behavior at room temperature. As the reaction temperature increased from 40 to 70 degrees C, the formation of magnetite nanotetrapods, nanorods, and nanoparticles was observed depending on the reaction temperatures. Magnetic properties of products were demonstrated to depend on the morphology, the degree of crystallinity, and the presence of amorphous oxyhydroxide. (C) 2009 The Electrochemical Society. [DOI: 10.1149/1.3125767] All rights reserved.

Preparation of human immune T cells containing iron-oxide nanoparticles was carried Out for the development of magnetically mediated immunotherapy. Peripheral blood lymphocytes (PBLs) after the incubation with magnetite nanoparticles were found to contain measurable ferric ions, which suggested the incorporation of magnetite nanoparticles. Transmission electron microscopic (TEM) study indicated that the incorporation of magnetite nanoparticles was mediated by endocytosis of PBLs. Furthermore, the effects of dosages and diameter of magnetite nanoparticles on the magnetite incorporation were investigated, and it was demonstrated that the increase in dosage promoted the incorporation of nanoparticles and the uptake into PBLs was more effective for magnetite nanoparticles, which formed smaller aggregations in medium. Finally, the demonstration of magnetite incorporation. into enriched T cells and tumor antigen-specific cytotoxic T lymphocyte (CTL) line promises the achievement of magnetically mediated immunotherapy with tumor-specific CTLs containing magnetic nanoparticles.

The present study aims at extending the possibility of utilizing bulky molecules such as proteins for fabricating electrochemical chiral sensors using an indium tin oxide (ITO) electrode. Enantioselective potential response of the human serum albumin (HSA)-modified ITO electrode was observed for tryptophan (Trp) when HSA was immobilized on an ITO electrode surface modified with disuccinimidyl suberate (DSS). In this sensing system. the enantioselective interaction between HSA and Trp is detected through the chemically reactive DSS group immobilized on the ITO electrode. (C) 2008 Elsevier B.V. All rights reserved.

Nanoparticles of FePt were prepared in two different ionic liquids (ILs). Because IL serves not only as a solvent but also as a surfactant, the particles prepared could be dispersed stably in hexane without adding other surfactants. The size distribution of the particles was found to be narrow without depending oil a size-selection process such as centrifugation. In addition, the particle sizes and composition were found to depend on the kind of IL employed.

The stereospecificity of a self-assembled monolayer (SAM) of homocysteine formed on the (111)-oriented gold surface toward the molecules with two chiral centers was investigated. Redox behaviors of catechins, which are electrochemically active molecules with two chiral centers, were analyzed with cyclic voltammetry by using a gold electrode modified with one enantiomeric form of homocysteine. The homocysteine SAM of one enantiomeric form was demonstrated to block the redox reaction of one enantiomer of catechin or epicatechin greater than that of the other, with cross inversion for the other enantiomer, in acidic solution. In addition, the homocysteine SAM on the gold electrode was suggested to recognize the chirality of one of the two chiral centers in catechin and epicatechin. (C) 2008 Elsevier Ltd. All rights reserved.

The process of preparation of FePt nanoparticles was investigated with emphasis on the effect of "growth temperature," at which the atomic diffusion between Pt-rich and Fe-rich phases leads to the formation of uniform nanoparticles. Consequently, it was demonstrated that by controlling, the growth temperature, the shape and crystallinity of FePt nanoparticles can be controlled. Oil the other hand, the size and composition were almost invariable at 5.6 +/- 0.5 nm and Fe53Pt47. respectively.

The effect of pH on the enantiospecificity of An (111) electrode modified with L-homocysteine was evaluated for the electrochemical redox reaction of 3,4-dihydroxyphenylalanine (DOPA). Cyclic voltammetric peaks clearly exhibited enantiospecificity at pH 0.6 and 2, whereas no enantiospecificity was observed at pH 3, 4, and 5.5. Scanning tunneling microscopy confirmed the highly ordered (2 root 3 x 3 root 3)R30 degrees structure of L-homocysteine at pH 0.6, at which L-homocysteine molecules form a dimer through the hydrogen-bond between carboxy groups (COOH), while a disordered structure was observed at pH 5.5. These results suggest that the dimer formed in the acidic solutions at pH below 3 plays an important role in providing the enantiospecificity to the Au(111) surface.

Synthesis of An nanoparticles (NPs) and their immobilization on optical waveguide (OWG) made of quartz plate were carried out aiming at application to sensing. Au NPs with diameters of similar to 5 nm and similar to 20 nm were synthesized by reduction of tetrachloroaurate ions with borohydride and immobilized on quartz OWG coated with monolayer of organosilane. With the OWG spectroscopy, the surface plasmon absorption of the An NPs immobilized on OWG was suggested to be influenced by the particle size and the interparticle distance and to response to the refractive index of nanoparticle proximity sensitively. (C) 2007 Elsevier B.V. All rights reserved.

An organic molecular sensor with a plasmon antenna was developed. A coaxial Ag grating antenna was designed by a finite differential time domain (FDTD) calculation and fabricated by a lift-off process. When pumping light was irradiated onto the sensor, a surface plasmon wave was generated and focused at the center of the antenna
this wave produced a strong electric field. By coating a cystamine self-assembled monolayer (SAM) onto the sensor, strong Raman scattering light produced by a surface-enhanced Raman scattering (SERS) effect was observed at the center of the device. The Raman spectrum showed good agreement with that of cystamine on a Ag surface. The Raman intensity at the center of the device increased significantly and was more than 2,000 times that outside the device. Our optical sensor can detect an unknown single molecule and can be incorporated into other sensors such as gas sensors and biosensors. © The Electrochemical Society.

Nanoparticles of Fe3O4 were synthesized by hydrolysis in an aqueous solution containing ferrous and ferric salts at various ratios with 1,6-hexanediamine as a base. It was found that the ferrous to ferric ratio influences the reaction mechanism for the formation of Fe3O4. When the ratio of ferrous to ferric ions was increased, the formation of large hydroxide particles as a precursor of Fe3O4 was promoted, which resulted in an increase in the size of Fe3O4 nanoparticles. As a result, the mean diameter of Fe3O4 nanoparticles increased from similar to 9 to similar to 37 nm as the molar percentage of ferrous ions with respect to the total iron ions was increased from 33 to 100%. Furthermore, it was demonstrated that magnetic properties of Fe3O4 nanoparticles can be controlled by adjusting the molar ratio of ferrous to ferric ions as well as the particle diameter. (C) 2007 Elsevier Inc. All rights reserved.

The enantioselectivity imparted to a gold electrode by modifying its surface with a self-assembled monolayer (SAM) of cysteine (Cys) was investigated for the electrochemical redox reaction of 3,4-dihydroxyphenylalanine (DOPA). A cyclic voltammetric study of the redox reaction revealed that the enantioselectivity was determined by the surface coverage of the gold electrode with Cys molecules. The electrode modified with similar to 1.8 x 10(14) Cys molecules cm(-2) exhibited enantioselectivity in the voltammogram. for the oxidation and reduction of DOPA, while the voltammograms obtained by the electrodes with either more or less surface coverages did not exhibit significant enantioselectivity. It is suggested that the accessibility of DOPA to that area of the gold surface which is not blocked by Cys molecules at an optimum surface coverage, is required for the enantioselective redox reaction of DOPA to proceed.

An extremely enhanced enantioselectivity was achieved for the detection of enantiomers of alanine (Ala), leucine (Leu), and 3,4-dihydroxyphenylalanine (DOPA) based on the voltammograms for the deposition of Cu from Cu complexes of the amino acids at an Au electrode modified with a self-assembled monolayer (SAM) Of L-homocysteine (Hcy). The enantioselective current density peak for the Cu deposition was found to change with increasing number of potential cycles after the addition of Cu(II), and the highest enantioselectivity was observed immediately after the addition of Cu(II). Besides, enantio selectivity was not observed with proline, whose five-membered ring contains the nitrogen atom of a secondary amino group, while some amino acids with a primary amine group such as Ala, Leu, and DOPA exhibited enantioselectivity. These results suggest that the chiral ligand exchange reaction at the L-Hcy SAM-modified Au electrode, namely, the enantioselective formation of diastereomeric complexes of Cu(II) with target enantiomers and L-Hcy self-assembled on the Au electrode, plays an important role in the chiral discrimination based on the Cu deposition. (c) 2006 Elsevier B.V. All rights reserved.

Structural and energetic investigations based on semiempirical PM5 and ab initio HF and MP2 calculations suggested that the self-assembled monolayer of an atropisomeric compound, (R)- or (S)-1,1'-binaphthalene-2,2'-dithiol (BNSH), on a gold (1 1 1) surface selectively adsorbs one enantiomer of phenylalanine (Phe), resulting in chiral discrimination, through hydrophobic, cation(-NH3+)-pi and NH(Phe)-pi (BNSH) interactions in a nanometer-sized screw-hole-like pocket composed of three BNSH molecules in the monolayer. (c) 2006 Elsevier B.V. All rights reserved.

The chemical reduction of ferrous or ferric ions to metallic iron by a reducing agent such as sodium borohydride (NaBH4), hydrazine (N2H4), or sodium phosphonate (NaH2PO2) and its subsequent oxidation were investigated for the preparation of iron-oxide nanoparticles in reverse micelles. The crystal structure and crystallinity of the oxide nanoparticles were found to depend on the oxidation potential of the reducing agent and the catalytic activity of the surface of deposited iron. In addition, it was demonstrated that the process used for oxidizing the metallic iron was critical for the formation of oxide nanoparticles, and that the enhancement of magnetic properties was achieved by providing a flow of oxygen during the oxidation process. (c) 2006 Elsevier Ltd. All rights reserved.

Crystallization of chiral amino acid, leucine, on the gold substrate modified with a self-assembled monolayer (SAM) was investigated with X-ray diffraction (XRD) and atomic force microscopy (AFM). It was found that the formation of enantiomeric crystalline phase occurred enantioselectively when the specimen modified with the SAM, to which one enantiomeric form of leucine molecules was covalently attached, was immersed in a pure enantiomeric solution of leucine. On the contrary, a racemic crystalline phase was formed on both D- and L-leucine-attached SAMs after soaking in a racemic leucine solution. In non-racemic solutions, both enantiomeric and racemic crystalline phases were formed on the enantiomer-attached SAM when the one enantiomeric form with the same chirality as the attached enantiomer was contained in excess, while neither of the crystals was formed with the other enantiomeric form in excess. Changes in the surface morphology of the specimens accompanied with the growth of crystalline phases on the SAM, reflecting the crystallinity suggested from the XRD method, were observed by using AFM. (c) 2006 Elsevier B.V. All rights reserved.

The effect of the surface morphology of gold-deposited quartz substrate on the enantioselective crystallization of leucine was investigated by using quartz crystal microbalance (QCM) and X-ray diffraction methods. The gold substrate was modified with a self-assembled monolayer with covalently attached D-leucine molecules. For a rough surface with root-mean-square (RMS) roughness of 17 nm, the QCM measurement showed a continuous decrease in frequency, while for a smooth surface with RMS roughness of 2 nm, essentially no change in frequency was observed. Nevertheless, leucine crystals with high crystallinity were clearly formed on the smooth surface.

An investigation was carried out on the surface modification of gamma-Fe2O3 nanoparticles with aminopropylsilyl (APS) groups in 3-aminopropyltriethoxysilane and the interparticle linkage with alpha,omega-dicarboxylic acids (succinic acid and suberic acid) through the terminal amino groups of APS moiety at the surface of gamma-Fe2O3 nanoparticles. It was demonstrated that the change in interparticle distance caused by these surface modifications influences the magnetic property of the composites. When gamma-Fe2O3 nanoparticles were modified with APS groups, coercivity increased and when they were further modified with alpha,omega-dicarboxylic acids, the larger decrease in coercivity was observed with the longer dicarboxylic acid. (C) 2005 Elsevier Ltd. All rights reserved.

Effects of the conventional bath additives [chloride ions (Cl-), poly(ethylene glycol) (PEG), bis(3-sulfopropyl)disulfide(SPS), and Janus green B (JGB)] used in the damascene process on the filling of submicrometer trenches with electrodeposited copper were investigated by electrochemical polarization measurement and cross-sectional microscopy. The combination of Cl- and PEG inhibited copper deposition in the areas of opening of the trenches, while SPS accelerated it at the bottom. Polarization curves showed that the degree of acceleration of copper deposition by SPS increases with the concentration of SPS. This SPS concentration- dependent acceleration accounts for the observed bottom- up growth. The addition of JGB inhibited copper deposition at the later stages of the filling process, leading to the suppression of the overfill phenomenon, although the bottom-up growth was also inhibited at high JGB concentrations. Bath agitation significantly enhanced the inhibition effect of JGB on the overfill phenomenon, without disturbing the bottom-up growth. (c) 2005 The Electrochemical Society. All rights reserved.

Chiral discrimination between thalidomide enantiomers was achieved using the self-assembled monolayer (SAM) of an atropisomeric compound, 1,1'-binaphthalene-2,2'-dithiol (BNSH), which takes a two-dimensional chiral arrangement on gold (111) surface. Interestingly, an "all-or-none" type enantioselectivity appears; one enantiomeric form of BNSH SAM allows the adsorption of only one enantiomer of thalidomide. In addition, the response of a racemic SAM of BNSH was revealed to be one-half of that caused by pure enantiomeric SAM. (C) 2004 Wiley-Liss, Inc.

Nanometer-size particles of iron oxide were prepared by a successive reduction-oxidation of ferric or ferrous ions within reverse micelles. Nanoparticles of iron oxide were collected from reverse micellar solution as precipitates by adding modifier molecules. The X-ray diffraction patterns and magnetic properties of thus-prepared samples suggested the formation of nanocrystalline phase of maghemite, gamma-Fe2O3.

An application of electrodeposited CoNiFeMoC soft magnetic thin films, which have high saturation magnetic flux density and high resistivity, to the magnetic recording head was investigated. Because the ductility of the CoNiFeMoC films was low, the head core using the CoNiFeMoC films was difficult to be prepared without being cracked. The ductility of CoNiFeMoC films was improved by the addition of saccharin in the bath which lowered carbon content of the films. By using such ductility-enhanced CoNiFeMoCS thin films, the structure of the magnetic recording head was successfully fabricated with no cracks.

Thermal desorption high-resolution mass spectrometry (TD-HRMS) is examined as a characterization tool for mixed self-assembled monolayers (SAMs) on gold. TD-HRMS provides a novel spectral view of the adsorption state of thiol and dithiol on gold, and it is confirmed in this study that thiolates, not thiols, are formed on the surface of gold by chemical bonding. Mass shifts in the TD-HRMS spectra indicate the number of Au-S bonds per thiol molecule and allow the accurate identification of the molecular formula of both single and mixed SAMs. The technique is also successfully used to observe the symmetric and asymmetric dimerization between constituent molecules of the SAM on gold. TD-HRMS is shown to provide information regarding the thermal desorption behavior of mixed SAMs, with clear distinctions between chemisorbed molecules and physisorbed molecules. TD-HRMS is demonstrated to be a useful means of estimating the surface molar ratio of mixed SAMs in that the molar ratio of mixed SAMs on gold is directly reflected in the obtained molecular ion intensity of constituent alkanethiols.

A pulsed electrodeposition method was applied to the preparation of soft magnetic CoNiFe films in the compositional region corresponding to the phase boundary between face-centered cubic (fcc) and body-centered cubic (bcc) structures. Crystalline grain size was found to be almost the same, smaller than 10 nm, and independent of the duty cycle which is the ratio of the pulse-on time to the pulse-on plus pulse-off period. Depending on the operating conditions, the ratio of bcc to fee varied. Current efficiency decreased with decreasing duty cycle and pulse current density. The intensity ratio of bcc(110) to fcc(111) X-ray diffraction peaks showed a maximum at the operating conditions in which the transition from kinetic to mass-transfer controlled deposition occurred with only a slight increase of Fe content (approximately 1 atom %). Magnetic properties were suggested to be controllable by adjusting the bce-fcc ratio using pulsed electrodeposition. (C) 2001 The Electrochemical Society.

Controlling the very small amount of inclusion of impurity elements by addition to the plating bath of various organic additives was found to be very effective in developing electrodeposited high-B-s CoNiFe soft magnetic thin films with desirably high resistivity. Included impurities were suggested to cause not only electron scattering but also decreasing grain size, both of which led to an increase of the resistivity. Chemical state of impurities was indicated to be controllable by selection of additives based on the functional group for adsorption.

The microstructural and crystallographic characteristics of electroplated soft magnetic CoNiFe thin films were investigated by transmission electron microscopy. Dark field images showed that the film with fcc-bcc dual crystals has a smaller grain size than the fee or bcc single phase film. The fee films were found to have a unique microstructure with twin-like stacking faults with relatively uniform grain size distribution, and such twins were also found in the dual phase films. Some coarse grains were found in the bcc films with a twin-free microstructure. The film prepared from the thiourea bath had a smaller grain size than that of the film from the saccharin bath. It is suggested from the diffraction patterns that the fee and bcc components of the films are substitutional solid solutions of Co, Ni and Fe. The lattice constants of fee CoNiFe films are determined by atomic concentrations of the three elements. The crystal structures of bcc films are determined by Fe, and the lattice constants are slightly changed by the incorporation of Co and Ni into the bcc lattice of Fe. The CoNiFe films obtained from saccharin and thiourea baths have different lattice constants, because of different sulfur contents of the films. (C) 2001 Elsevier Science B.V. All rights reserved.

The thermal stability and high-frequency permeability of high-B-s CoNiFe thin films were investigated, CoNiFe films exhibited excellent soft magnetic properties and good thermal stability up to 350 degrees C, Annealing in longitudinal magnetic field enabled to achieve H-k as high as 35 Oe, while the H-k value after annealing in a transverse magnetic field was less than 20 Oe, By suppressing the core loss, the effective permeability of high-B-s CoNiFe thin film at high frequencies was improved successfully.

In order to increase the resistivity of electrodeposited high-B-s CoNiFe thin film, an organic additive such as diethylenetriamine (DET) was added to the plating bath. The desirable soft magnetic CoNiFe film with higher rho value of 95 mu Omega-cm was developed by the carbon inclusion from the new bath containing DET. The CoNiFe thin film with high rho value exhibited the excellent frequency-dependence of the permeability. Although high-rho CoNiFe thin film did not show the sufficient corrosion resistance, annealing at 250 degrees C for one hour in vacuum led to higher anticorrosion property.

Addition of a complexing agent and/or Na₂MoO₄ to the bath was investigated with a view to increasing the resistivity of CoNiFe soft magnetic thin films. Results showed that the electrical resistivity of CoNiFe thin films was increased by addition of a complexing agent such as sodium tartrate and sodium citrate. These films contained a small amount of carbon of 1 to 2 at%. The addition of Na₂MoO₄ also resulted in an increase in resistivity of CoNiFe thin films. This Co₅₉Ni₁₂Fe₂₆Mo₁C₂ thin film had the following properties: B_s = 1.8 T, H_c = 1.6 Oe, ρ = 129 μΩcm.

In order to increase the resistivity of electrodeposited high B-S CoNiFe thin film, the effect of an organic additive such as diethylenetriamine (DET) added to the plating bath was investigated. The values of rho and H-C were gradually increased as a function of DET concentration. The desirable soft magnetic CoNiFe thin film with rho = 25-90 mu Omega-cm under the conditions of B-S > 1.9 T and H-C < 2.5 Oe was developed as function of carbon in the deposited films. Additionally, the high resistivity CoNiFe thin film with rho = 130 mu Omega-cm was established under the conditions of B-S = 1.7 T and H-C < 6 Oe.

Monolayers of CdS and ZnS nanoparticles and their layer-by-layer composite films were fabricated on a gold substrate that was precoated with a self-assembled monolayer (SAM) of 1,6-hexanedithiol. Semiconductor nanoparticles (similar to 4 nm in diameter) were prepared in reversed micelles. Evidence for the attachment of nanoparticles on SAM was obtained by X-ray photoelectron spectroscopy. A photoinduced anodic current was observed when the semiconductor nanoparticle electrodes were immersed in an electrolyte solution containing triethanolamine as the electron donor. The photocurrent action spectra of nanoparticle monolayers were in good agreement with the absorption spectra of nanoparticle dispersions before immobilization, indicating that the nanoparticles were immobilized on the substrate without changing their particle size. Layer-by-layer composite films of CdS and ZnS showed photoresponse depending on the order of accumulation. This indicates the successful fabrication of a layer-by-layer structure that affects the electron transfer through nanoparticles and the penetration of the electrolyte solution.

The redox potential of molybdenum oxides in alkali borate melts was studied using the cyclic voltammetry. In the Na2O-B2O3 melts, where the Na2O activity had been previously measured and the basicity was defined as pO= -log a (Na2O), the redox potential corresponding to Mo(VI)/Mo shifted to the positive side as the melts became more acidic, linearly depending on the basicity of the solvent melts. We succeeded in quantitatively interpreting this behavior from a thermodynamic viewpoint. In other alkali borate melts, R2O-B2O3 (R=Li, K and Cs), the redox potential shifted to the negative side when alkali was exchanged from lithium and potassium to cesium at the same composition. It is shown that the redox potential of Mo(VI)/Mo can be applicable to determine the basicity in high temperature melts in general.

Layer-by-layer self-assembly of composite thin films of cadmium sulfide (CdS) nanoparticle and alkanedithiol was achieved on a gold substrate by an alternate immersion into solutions of dithiols (1,6-hexanedithiol and 1,10-decanedithiol) and solution containing CdS nanoparticles (ca. 3 nm in diameter). The layer-by-layer structure was confirmed by angle-resolved X-ray photoelectron spectroscopy (XPS) at each composite-film preparation step. The proposed structure and mechanism of self-assembly were in agreement with our previous results obtained by Fourier transform infrared reflection-absorption spectroscopy. (C) 1997 Elsevier Science B.V.