Vertically aligned MXene bioelectrode prepared by freeze-drying assisted electrophoretic deposition for sensitive electrochemical protein detection.

Two-dimensional (2D) carbides, MXenes, have attracted attention as electrode materials of electrochemical biosensors because of their metallic conductivity, hydrophilicity, and mechanical stability. However, when fabricating electrodes, the nanosheets tend to re-stack and generally align horizontally with respect to the current collector due to the highly anisotropic nature of MXene, resulting in low porosity and poor utilization of the MXene surface. Here we report the electrochemical biosensing of antibody-antigen reactions with a vertically aligned Ti3C2Tx MXene (VA-MXene) electrode prepared by freeze-drying assisted electrophoretic deposition. The macroporous VA-MXene electrode exhibited a better electrochemical response towards the immunoreaction between the allergenic buckwheat protein (BWp16) and the antibody compared to a non-porous, horizontally (in-plane) stacked MXene (HS-MXene) and the sensors reported in the literature. The sensor responsiveness, defined as the ratio of the obtained current density of the electrode to the antigen concentration, was much higher for the VA-MXene electrode (238 µA cm-2 (ng mL-1) -1) than for the HS-MXene electrode. The proposed technique is applicable to other exfoliated nanosheets, and will open a new avenue for porous nanosheet electrodes to improve the sensing characteristics of electrochemical biosensors.

Zero-Overpotential Redox Reactions of Quinone-Based Molecules Confined in Carbon Micropores.

Quinone-based aromatic compounds have been studied as electrode materials for various energy-storage devices. However, the relatively large activation barrier of the charge-transfer process of these redox-active molecules causes sluggish reactions and a decrease in energy efficiency. To lower the activation barrier, aromatic compounds must be strongly adsorbed on the electrode surface, preferably via π-π stacking interactions. Molecules in slit-shaped micropores strongly adsorb on the graphitic walls, thus experiencing unique micropore-confinement properties. In this study, the micropore-confinement effect is extended to the adsorption of quinone-based redox-active molecules in 0.8 nm slit-shaped micropores of activated carbon, which produces a drastic reduction in the activation barrier of the charge-transfer process and creates a zero-overpotential redox reaction. The property originates from the short distance (approximately 0.3 nm) between the quinone molecules and the graphitic wall due to the strong adsorption of the aromatic compound. Our results provide the first demonstration that the micropore-confinement effect can reduce and nearly eliminate the activation barrier of an electrochemical reaction. We also demonstrate the applicability of this approach via the charge/discharge performance of a two-electrode cell. Cells comprising the aromatic compound/activated carbon material as positive and negative electrodes exhibit a greater retention capacity than those without activated carbon. The technique described herein can guide the development of high-performance, rapid charging/discharging electrodes for energy-storage devices such as batteries, supercapacitors, and hybrid devices using organic materials.

Enhancement in the Charge-Transfer Kinetics of Pseudocapacitive Iridium-Doped Layered Manganese Oxide.

Birnessite manganese oxide is a promising candidate as an electrode material for aqueous supercapacitors owing to its pseudocapacitance associated with fast redox processes. While manganese oxides are semiconductive, the conductivity is much lower than that of typical materials used for capacitive electrodes such as activated carbon or ruthenium oxide. In an attempt to increase the electronic conductivity of birnessite, a new solid solution phase, Ky(Mn1-xIrx)O2, was synthesized, and the electrochemical charge storage capability of Ir-doped birnessite was studied in aqueous Li2SO4. Structural characterization revealed that the single-phase Ky(Mn1-xIrx)O2 could be synthesized up to x = 0.1. An increase in the pseudocapacitive charge was observed with the increase in Ir content. In addition to the increase in the pseudocapacitive charge, an unusual change in the peak potential was observed. The peak-to-peak difference for the Mn4+/Mn3+ redox decreased with increasing Ir content, indicating an increase in the reversibility of the pseudocapacitive process. The decrease in peak-to-peak difference was observed only by Ir substitution and was not observed for physical mixtures of K0.28MnO2 and IrO2, suggesting a strong electronic interaction between the host Mn ion and the substituting Ir ion.

Glycan-immobilized dual-channel field effect transistor biosensor for the rapid identification of pandemic influenza viral particles.

Pandemic influenza, triggered by the mutation of a highly pathogenic avian influenza virus (IFV), has caused considerable damage to public health. In order to identify such pandemic IFVs, antibodies that specifically recognize viral surface proteins have been widely used. However, since the analysis of a newly discovered virus is time consuming, this delays the availability of suitable detection antibodies, making this approach unsuitable for the early identification of pandemic IFVs. Here we propose a label-free semiconductor-based biosensor functionalized with sialic-acid-containing glycans for the rapid identification of the pandemic IFVs present in biological fluids. Specific glycans are able to recognize wild-type human and avian IFVs, suggesting that they are useful in discovering pandemic IFVs at the early stages of an outbreak. We successfully demonstrated that a dual-channel integrated FET biosensing system, which were modified with 6'-sialyllactose and 3'-sialyllactose for each gate area, can directly and specifically detect human H1N1 and avian H5N1 IFV particles, respectively, present in nasal mucus. Furthermore, to examine the possibility of identifying pandemic IFVs, the signal attributed to the detection of Newcastle disease virus (NDV) particles, which was selected as a prime model of a pandemic IFV, was clearly observed from both sensing gates. Our findings suggest that the proposed glycan-immobilized sensing system could be useful in identifying new pandemic IFVs at the source of an outbreak.

Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy.

Correction for 'Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a.

Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy.

Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 ± 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser irradiation. The AHP@MNPs can target tumors via CD44 receptor-mediated endocytosis, which have enhanced tumor therapeutic effects through photodynamic/hyperthermia-combined treatment without any drugs. We successfully detected tumors implanted in mice via magnetic resonance imaging and optical imaging. Furthermore, we demonstrated the photodynamic/hyperthermia-combined therapeutic efficacy of AHP@MNPs with synergistically enhanced efficacy against cancer.

Label-free detection of Cu(II) in a human serum sample by using a prion protein-immobilized FET sensor.

We have developed a field effect transistor (FET) sensor to sensitively detect copper ions (Cu(2+)) in a human serum (HS) sample for promising health-care diagnosis. By utilizing a Cu(2+)-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 Cu(2+) deficiency in practical applications.

Sensitive electrical detection of human prion proteins using field effect transistor biosensor with dual-ligand binding amplification.

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.

A label-free electrical assay of fibrous amyloid ß based on semiconductor biosensing.

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.

Field Effect Transistor Biosensor Using Antigen Binding Fragment for Detecting Tumor Marker in Human Serum.

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, α-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 µg/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.

Attomolar detection of influenza A virus hemagglutinin human H1 and avian H5 using glycan-blotted field effect transistor biosensor.

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-α2,6-galactose (6'-sialyllactose) and in sialic acid-α2,3-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.

Fabrication of stable antibody-modified field effect transistors using electrical activation of Schiff base cross-linkages for tumor marker detection.

In this paper, we present a method of fabricating a rigid antibody-immobilized surface using electric activation of a glutaraldehyde (GA)-modified aminopropylsilyl surface for stable antibody-modified field effect transistors (FETs). Electric activation of the GA-modified gate surface of the FET reduces Schiff bases, which are easily hydrolyzed and collapsed, formed between GA and 3-aminopropyltriethoxysilane, resulting in preventing the immobilized antibodies from desorbing from the surface. The lack of Raman peaks that could be assigned to a Schiff base after the electrical activation of the GA-modified surface indicated that the electric activation had reduced the Schiff base. The use of the antibody-modified FETs has three advantages for the detection of antigens: increased sensitivity, distinct recognition ability, and improved reproducibility. A tumor marker, alpha-fetoprotein (AFP), was quantitatively detected up to a concentration of 10 ng/mL using the antibody-modified FET. The detection ability of the FET accomplished a cutoff value of hepatic cancer. The quantitative detection of AFP in a solution with contaminating proteins was also demonstrated. This electric activation method is applicable to other antibody-modified FETs.

Detection of biomolecular interaction between biotin and streptavidin on a self-assembled monolayer using magnetic nanoparticles.

For developing a magnetic bioassay system, an investigation to determine the presence of a specific biomolecular interaction between biotin and streptavidin was done using magnetic nanoparticles and a silicon substrate with a self-assembled monolayer. Streptavidin was immobilized on the magnetic particles, and biotin was attached to the monolayer-modified substrate. The reaction of streptavidin-modified magnetic particles on the biotin-modified substrate was clearly observed under an optical microscope. The magnetic signals from the particles were detected using a magnetic force microscope. The results of this study demonstrate that the combination of a monolayer-modified substrate with biomolecule-modified magnetic particles is useful for detecting biomolecular interactions in medical and diagnostic analyses.