Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Language：English   Publishing type：Research paper (scientific journal)  

Various liquid biopsy methods have been developed for the non-invasive and early detection of diseases. In particular, the detection of circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) in blood has been receiving a great deal of attention. We have been developing systems and materials to facilitate such liquid biopsies. In this study, we further developed glass filters (with various patterns of holes, pitches, and non-adhesive coating) that can capture CTCs, but not white blood cells. We optimized the glass filters to capture CTCs, and demonstrated that they could be used to detect CTCs from lung cancer patients. We also used the optimized glass filters for detecting CAFs. Additionally, we further developed a system for visualizing the captured cells on the glass filters. Finally, we demonstrated that we could directly culture the captured cells on the glass filters. Based on these results, our high-performance glass filters appear to be useful for capturing and culturing CTCs and CAFs for further examinations.

DOI： 10.1038/s41598-023-31265-9

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Extracellular vesicles (EVs) have promising potential as biomarkers for early cancer diagnosis. The EVs have been widely studied as biological cargo containing essential biological information not only from inside vesicles such as nucleic acids and proteins but also from outside vesicles such as membrane proteins and glycolipids. Although various methods have been developed to isolate EVs with high yields such as captures based on density, size, and immunoaffinity, different measurement systems are needed to analyze EVs after isolation, and a platform that enables all-in-one analysis of EVs from capture to detection in multiple samples is desired. Since a nanowire-based approach has shown an effective capability for capturing EVs via surface charge interaction compared to other conventional methods, here, we upgraded the conventional well plate assay to an all-in-one nanowire-integrated well plate assay system (i.e., a nanowire assay system) that enables charge-based EV capture and EV analysis of membrane proteins. We applied the nanowire assay system to analyze EVs from brain tumor organoids in which tumor environments, including vascular formations, were reconstructed, and we found that the membrane protein expression ratio of CD31/CD63 was 1.42-fold higher in the tumor organoid-derived EVs with a p-value less than 0.05. Furthermore, this ratio for urine samples from glioblastoma patients was 2.25-fold higher than that from noncancer subjects with a p-value less than 0.05 as well. Our results demonstrated that the conventional well plate method integrated with the nanowire-based EV capture approach allows users not only to capture EVs effectively but also to analyze them in one assay system. We anticipate that the all-in-one nanowire assay system will be a powerful tool for elucidating EV-mediated tumor-microenvironment crosstalk.

DOI： 10.1021/acsnano.2c08526

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acsmeasuresciau.2c00057

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cas.15597

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.2c01053

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/btm2.10388

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/s22155705

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Chemodynamic therapy (CDT), which consumes endogenous hydrogen peroxide (H2O2) to generate reactive oxygen species (ROS) and causes oxidative damage to tumor cells, shows tremendous promise for advanced cancer treatment. However, the rate of ROS generation based on the Fenton reaction is prone to being restricted by inadequate H2O2 and unattainable acidity in the hypoxic tumor microenvironment. We herein report a multifunctional nanoprobe (BCGCR) integrating bimodal imaging and photothermal-enhanced CDT of the targeted tumor, which is produced by covalent conjugation of bovine serum albumin-stabilized CuS/Gd2O3 nanoparticles (NPs) with the Cy5.5 fluorophore and the tumor-targeting ligand RGD. BCGCR exhibits intense near-infrared (NIR) fluorescence and acceptable r1 relaxivity (∼15.3 mM-1 s-1) for both sensitive fluorescence imaging and high-spatial-resolution magnetic resonance imaging of tumors in living mice. Moreover, owing to the strong NIR absorbance from the internal CuS NPs, BCGCR can generate localized heat and displays a high photothermal conversion efficiency (30.3%) under 980 nm laser irradiation, which enables photothermal therapy and further intensifies ROS generation arising from the Cu-induced Fenton-like reaction for enhanced CDT. This synergetic effect shows such an excellent therapeutic efficacy that it can ablate xenografted tumors in vivo. We believe that this strategy will be beneficial to exploring other advanced nanomaterials for the clinical application of multimodal imaging-guided synergetic cancer therapies.

DOI： 10.1021/acsami.2c06503

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Imaging technology based on novel nanomaterials is burgeoning as a potential tool for exploring various physiological processes. We herein report a fluorescent and magnetic nanoprobe (QMNP-RGD) for bimodal imaging of in vitro tumor cells. The preparation of this multifunctional nanomaterial is divided into three steps. First, commercial quantum dots (QDs) with high fluorescence intensity are covalently modified with an RGD peptide, which can facilitate the tumor cell uptake by αvβ3 integrin-induced active recognition. Superparamagnetic iron oxide (SPIO) nanoparticles (NPs) are then capped using a cationic polysaccharide to improve stability. Integration is finally achieved by convenient electrostatic binding. We successfully demonstrated that QMNP-RGD can be efficiently delivered into U87MG cells and used for fluorescence/magnetic resonance (MR) bimodal imaging. Other multimodal probes may be able to be designed for imaging based on this strategy of electrostatic binding.

DOI： 10.1007/s44211-022-00153-z

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

This paper is the first report of a non-competitive fluorescence polarization immunoassay (NC-FPIA) using a peptide as a tracer. The NC-FPIA can easily and quickly quantify the target after simply mixing them together. This feature is desirable for point-of-need applications such as clinical diagnostics, infectious disease screening, on-site analysis for food safety, etc. In this study, the NC-FPIA was applied to detect CD9, which is one of the exosome markers. We succeeded in detecting not only CD9 but also CD9 expressing exosomes derived from HeLa cells. This method can be applied to various targets if a tracer for the target can be prepared, and expectations are high for its future uses.

DOI： 10.1039/d2lc00224h

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/d1cc06384g

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/d2lc00113f

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/d2lc00112h

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Zinc oxide (ZnO) nanowires have shown their potential in isolation of cancer-related biomolecules such as extracellular vesicles (EVs), RNAs, and DNAs for early diagnosis and therapeutic development of diseases. Since the function of inorganic nanowires changes depending on their morphology, previous studies have established strategies to control the morphology and have demonstrated attainment of improved properties for gas and organic compound detection, and for dye-sensitized solar cells and photoelectric conversion performance. Nevertheless, crystallinity and morphology of ZnO nanowires for capturing EVs, an important biomarker of cancer, have not yet been discussed. Here, we fabricated ZnO nanowires with different crystallinities and morphologies using an ammonia-assisted hydrothermal method, and we comprehensively analyzed the crystalline nature and oriented growth of the synthesized nanowires by X-ray diffraction and selected area electron diffraction using high resolution transmission electron microscopy. In evaluating the performance of label-free EV capture in a microfluidic device platform, we found both the crystallinity and morphology of ZnO nanowires affected EV capture efficiency. In particular, the zinc blende phase was identified as important for crystallinity, while increasing the nanowire density in the array was important for morphology to improve EV capture performance. These results highlighted that the key physicochemical properties of the ZnO nanowires were related to the EV capture performance.

DOI： 10.1039/d1nr07237d

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The effects of increased confinement on the catalytic rates of individual enzyme molecules were studied at the single molecule level using femtolitre chambers and molecular crowders. According to the increase of confinement, from micro to nanometer cubic space in the chambers, the hydrolysis rate of β-galactosidase (β-gal) decreased to one-tenth of the rate in bulk. When molecular crowders suppressed the diffusion rates that reduced the collision chance of an enzyme and a substrate, the hydrolysis rate also decreased, which happened also in the case of femtolitre chambers. However, their kinetic trend was different especially from the viewpoint of the diffusion rates in diffusion-limited space. These data suggested that cell or organelle-scale confined environments might affect the kinetics of biochemical reactions and emphasized the importance of understanding enzyme kinetics in the in vivo environment.

DOI： 10.1039/d1an02024b

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Energy dissipation in solid-state nanopores is an important issue for their use as a sensor for detecting and analyzing individual objects in electrolyte solution by ionic current measurements. Here, we report on evaluations of heating via diffusive ion transport in the nanoscale conduits using thermocouple-embedded SiNx pores. We found a linear rise in the nanopore temperature with the input electrical power suggestive of steady-state ionic heat dissipation in the confined nanospace. Meanwhile, the heating efficiency was elucidated to become higher in a smaller pore due to a rapid decrease in the through-water thermal conduction for cooling the fluidic channel. The scaling law suggested nonnegligible influence of the heating to raise the temperature of single-nanometer two-dimensional nanopores by a few kelvins under the standard cross-membrane voltage and ionic strength conditions. The present findings may be useful in advancing our understanding of ion and mass transport phenomena in nanopores.

DOI： 10.1126/sciadv.abl7002

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Humidity and moisture effects, frequently called water poisoning, in surroundings are inevitable for various molecular sensing devices, strongly affecting their sensing characteristics. Here, we demonstrate a water-selective nanostructured dehumidifier composed of ZnO/TiO2/CaCl2 core-shell heterostructured nanowires for molecular sensing spaces. The fabricated nanostructured dehumidifier is highly water-selective without detrimental adsorptions of various volatile organic compound molecules and can be repeatedly operated. The thermally controllable and reversible dehydration process of CaCl2·nH2O thin nanolayers on hydrophilic ZnO/TiO2 nanowire surfaces plays a vital role in such water-selective and repeatable dehumidifying operations. Furthermore, the limitation of detection for sensing acetone and nonanal molecules in the presence of moisture (relative humidity ∼ 90%) was improved more than 20 times using nanocomposite sensors by operating the developed nanostructured dehumidifier. Thus, the proposed water-selective nanostructured dehumidifier offers a rational strategy and platform to overcome water poisoning issues for various molecular and gas sensors.

DOI： 10.1021/acssensors.1c02378

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Organ Preservation and Biology  

<p>Pulmonary fibrosis is known as a progressive disease in which the interstitium is damaged by some factor, resulting in fibrosis of the lungs and a gradual decline in respiratory function. There are very few treatments, various problems and it is not a fundamental treatment. On the other hand, regenerative medicine has attracted attention in recent years as a fundamental treatment for pulmonary fibrosis. In particular, stem cell transplantation using mesenchymal stem cells have already begun to be applied clinically as a regenerative medicine method for many diseases, as they are relatively easy to harvest from living organisms and have a low risk of tumorigenesis and high safety. However, to establish stem cell transplantation, it is important to clarify the in vivo behavior and accumulation sites of transplanted stem cells. In this study, therefore, to ensure the safety and high therapeutic efficacy of stem cell transplantation for pulmonary fibrosis, adipose tissue-derived mesenchymal stem cells labelled with quantum dots, the most advanced fluorescent nanomaterial, were administered to bleomycin pulmonary fibrosis model mice, and the in vivo behavior and therapeutic efficacy of the transplanted stem cells were investigated.</p>

DOI： 10.11378/organbio.29.138

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Cancer-derived small extracellular vesicles (sEVs) are multifunctional particles with a lipid bilayer structure that are involved in cancer progression, such as malignant proliferation, distant metastasis, and cancer immunity evasion. The separation protocol used to isolate sEVs is an important process and thus, several have been developed, including ultracentrifugation (UC), size exclusion chromatography (SEC), and affinity purification using antibodies against sEV surface antigens. However, the effects of different separation methods on sEV components have not been adequately examined. Here, we developed a semi-automated system for collecting sEVs by combining SEC and preparative high-performance liquid chromatography and applied it to metabolome analysis. The developed SEC system could recover sEVs more efficiently and non-destructively than UC, suggesting that it is an appropriate recovery method for metabolic analysis and reflects biological conditions. Furthermore, using the developed SEC system, we performed metabolome analysis of sEVs from isocitrate dehydrogenase 1 (IDH)-mutated human colon HCT116 cells, which produce the oncogenic metabolite, 2-hydroxyglutaric acid (2-HG). IDH1-mutated HCT116 cells released significantly more sEVs than wild-type (WT) cells. The metabolomic profiles of IDH1 mutant and WT cells showed distinct differences between the cells and their sEVs. Notably, in IDH mutant cells, large amounts of 2-HG were detected not only in cells, but also in sEVs. These results indicate that the SEC system we developed has wide potential applications in sEVs research.

DOI： 10.3389/fmolb.2022.1049402

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Language：English   Publishing type：Research paper (scientific journal)  

The study of the multimolecular crowding around cancer cells has opened up the possibility of developing new devices for cancer diagnosis and analysis through the measurement of intercellular communication related to cell proliferation and invasive metastasis associated with cancer malignancy. In particular, cells and extracellular vesicles that flow into the bloodstream contain metabolites and secreted products of the cancer microenvironment. These are positioned as targets for the development of new devices for the understanding and application of multimolecular crowding around cancer cells. Examples include the separation analysis of cancer cells in blood for the next generation of less invasive testing techniques, and mapping analysis using Raman scattering to detect cancer cells without staining. Another example is the evaluation of the relationship between exosomes and cancer traits for the exploration of new anti-cancer drugs, and the commercialization of exosome separation devices for ultra-early cancer diagnosis. The development of nanobiodevice engineering, which applies multimolecular crowding to conventional nanobioscience, is expected to contribute to the diagnosis and analysis of various diseases in the future.

DOI： 10.1039/d1cc05556a

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Nanowire microfluidics using a combination of self-assembly and nanofabrication technologies is expected to be applied to various fields due to its unique properties. We have been working on the fabrication of nanowire microfluidic devices and the development of analytical methods for biomolecules using the unique phenomena generated by the devices. The results of our research are not just limited to the development of nanospace control with "targeted dimensions" in "targeted arrangements" with "targeted materials/surfaces" in "targeted spatial locations/structures" in microfluidic channels, but also cover a wide range of analytical methods for biomolecules (extraction, separation/isolation, and detection) that are impossible to achieve with conventional technologies. Specifically, we are working on the extraction technology "the cancer-related microRNA extraction method in urine," the separation technology "the ultrafast and non-equilibrium separation method for biomolecules," and the detection technology "the highly sensitive electrical measurement method." These research studies are not just limited to the development of biomolecule analysis technology using nanotechnology, but are also opening up a new academic field in analytical chemistry that may lead to the discovery of new pretreatment, separation, and detection principles.

DOI： 10.1039/d1cc05096f

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PubMed

Language：English   Publishing type：Research paper (international conference proceedings)  

Language：English   Publishing type：Research paper (international conference proceedings)  

Language：English   Publishing type：Research paper (international conference proceedings)  

Language：English   Publishing type：Research paper (international conference proceedings)  

Language：English   Publishing type：Research paper (international conference proceedings)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Multinary semiconductor quantum dots (QDs) composed of group I-III-VI elements have received much attention for wide-ranging applications due to their low level of toxicity and tunable optical properties. The chemical composition and particle size are important parameters for controlling the physicochemical properties of these QDs. In this study, we prepared quinary QDs of an Ag-(In,Ga)-(S,Se) semiconductor (AIGSSe) by thermolysis of precursors in an organic solution with two-step heat treatment and evaluated their physicochemical properties as a function of Se fraction. The energy gap (Eg) of QDs decreased from 1.9 to 1.5 eV with an increase in the Se/(S + Se) ratio from 0 to 1, accompanied by a shift of the valence band maximum to a higher energy level. The obtained AIGSSe QDs exhibited a sharp band-edge PL peak, the wavelength of which was red-shifted from 580 to 790 nm with a decrease in theirEg. The PL intensity was remarkably enlarged by the surface coating with a GaSxshell, the highest PL quantum yield being 50% for the PL peak at 580 nm. AIGSSe QDs with an Se/(S + Se) ratio of 0.50 exhibited a near-IR PL peak at 790 nm, which is suitable forin vivobioimaging in the wavelength range of the first biological window. By incorporating GaSx-coated AIGSSe QDs (Se/(S + Se) = 0.50) into liposomes, the QDs were transferred into aqueous solutions without significant deterioration of both the PL peak outline and quantum yield, though a broad PL peak originating from defect sites appeared with a relatively large PL intensity when GaSx-coated Ag-(In,Ga)-S QDs that did not contain Se were used.In vivoimaging of a mouse was successfully performed by detecting the band-edge emission at 790 nm of AIGSSe QDs injected subcutaneously in the back of the mouse.

DOI： 10.1039/d1tc02746h

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Language：English   Publishing type：Research paper (scientific journal)  

This study developed low‐cost and highly sensitive immunoassay devices possessing the ability to rapidly analyze urine samples. Further, they can quantitatively detect three biomarkers indicating renal injury: monocyte chemotactic protein 1 (MCP‐1), angiotensinogen (AGT), and liver-type fatty acid binding protein (L‐FABP). The devices were used to successfully estimate the concentrations of the three biomarkers in urine samples within 2 min; the results were consistent with those obtained via conventional enzyme‐linked immunosorbent assay (ELISA), which requires several hours. In addition, the estimated detection limits for the three biomarkers were comparable to those of commercially available ELISA kits. Thus, the proposed and fabricated devices facilitate high‐precision and frequent monitoring of renal function.

DOI： 10.3390/mi12111353

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER ADVANCED TECHNOLOGY  

Extracellular vesicles (EVs) have shown promising features as biomarkers for early cancer diagnoses. The outer layer of cancer cell-derived EVs consists of organotropic metastasis-induced membrane proteins and specifically enriched proteoglycans, and these molecular compositions determine EV surface charge. Although many efforts have been devoted to investigating the correlation between EV subsets obtained through density-, size-, and immunoaffinity-based captures and expressed membrane proteins, understanding the correlation between EV subsets obtained through surface charge-based capture and expressed membrane proteins is lacking. Here, we propose a methodology to profile membrane proteins of EV subsets obtained through surface charge-based capture. Nanowire-induced charge-based capture of EVs and in-situ profiling of EV membrane proteins are the two key methodology points. The oxide nanowires allowed EVs to be obtained through surface charge-based capture due to the diverse isoelectric points of the oxides and the large surface-to-volume ratios of the nanowire structures. And, with the ZnO nanowire device, whose use does not require any purification and concentration processes, we demonstrated the correlation between negatively-charged EV subsets and expressed membrane proteins derived from each cell. Furthermore, we determined that a colon cancer related membrane protein was overexpressed on negatively charged surface EVs derived from colon cancer cells.

DOI： 10.1016/j.bios.2021.113589

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Amplification-free genome analysis can revolutionize biology and medicine by uncovering genetic variations among individuals. Here, the authors report on a 3D-integrated nanopore for electrolysis to in situ detection of single-molecule DNA in a cell by ionic current measurements. It consists of a SiO2 multipore sheet and a SiNx nanopore membrane stacked vertically on a Si wafer. Single cell lysis is demonstrated by 106 V m−1-level electrostatic field focused at the multinanopore. The intracellular molecules are then directly detected as they move through a sensing zone, wherein the authors find telegraphic current signatures reflecting folding degrees of freedom of the millimeter-long polynucleotides threaded through the SiNx nanopore. The present device concept may enable on-chip single-molecule sequencing to multi-omics analyses at a single-cell level.

DOI： 10.1002/smtd.202100542

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/smtd.202100542

Language：English   Publishing type：Research paper (scientific journal)  

Since DNA analysis is the fundamental process for most applications in biomedical fields, capturing DNAs with high efficiency is important. Here, we used several oxide nanowire microfluidic devices to capture CpG-rich single-stranded DNAs (ssDNAs) in different pH solutions. All the oxide nanowires exhibited the highest capture efficiency around pH 7 with good capture efficiency shown by each metal oxide; ZnO/ZnO core/shell NWs (71.6%), ZnO/Al2O3 core/shell NWs (86.3%) and ZnO/SiO2 core/shell NWs (86.7%). ZnO/Al2O3 core/shell NWs showed the best performance for capturing ssDNAs under varying pH, which suggests its suitability for application in diverse biological fluids. The capturing efficiencies were attributed to the interactions from phosphate backbones and nucleobases of ssDNAs to each nanowire surface. This finding provides a useful platform for highly efficient capture of the target ssDNAs, and these results can be extended for future studies of cancer-related genes in complex biological fluids.

DOI： 10.2116/analsci.20P421

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We investigated the microfabrication of PCR reaction vessel, capillary array electrophoresis (CAE), and laser-induced fluorescence detection cell using synchrotron radiation in polymethylmethacrylate (PMMA) substrates towards the development of novel technology for ultra-fast DNA analysis. Laser-induced fluorescence detection system for the chip has been developed and successfully applied to the imaging of a band for DNA fragment labeled by fluorescent dye during migrating in the array of microchannels to optimize the separation conditions for DNA analysis. Based on the imaging data, we can estimate that 10-s separation of some DNA fragments will be achievable using 10-mm separation channel on a chip.

DOI： 10.1016/S0928-4931(00)00154-5

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Language：English   Publishing type：Research paper (scientific journal)  

RNA analytical platforms gained extensive attention recently for RNA-based molecular analysis. However, the major challenge for analyzing RNAs is their low concentration in blood plasma samples, hindering the use of RNAs for diagnostics. Platforms that can enrich RNAs are essential to enhance molecular detection. Here, we developed the annealed ZnO/Al2O3 core-shell nanowire device as a platform to capture RNAs. We showed that the annealed ZnO/Al2O3 core-shell nanowire could capture RNAs with high efficiency compared to that of other circulating nucleic acids, including genomic DNA (gDNA) and cell-free DNA (cfDNA). Moreover, the nanowire was considered to be biocompatible with blood plasma samples due to the crystalline structure of the Al2O3 shell which serves as a protective layer to prevent nanowire degradation. Our developed device has the potential to be a platform for RNA-based extraction and detection.

DOI： 10.3390/nano11071768

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Methods that can rapidly and accurately extract or isolate nucleic acids would facilitate the capability for scientists to access key information regarding nucleic acid molecular signatures. Knowing these molecular signatures could contribute to development of strategies for detecting, treating, and diagnosing diseases based on nucleic acids. However, major impediments to accessing nucleic acids are their natural characteristics, including concentration and size. Here we review the development of nanomaterial-based devices to isolate circulating nucleic acids from biological samples, including blood, urine, cell, and virus; these devices enable enhancement of isolation and extraction efficiency compared to conventional methods.

DOI： 10.1246/cl.210066

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI  

Field-effect transistors (FETs) are attractive biosensor platforms for rapid and accurate detection of various analytes through surface immobilization of specific bio-receptors. Since it is difficult to maintain the electrical stability of semiconductors of sensing channel under physiological conditions for long periods, passivation by a stable metal oxide dielectric layer, such as Al2O3 or HfO2, is currently used as a common method to prevent damage. However, protecting the sensing channel by passivation has the disadvantage that the distance between the target and the conductive channel increases, and the sensing signal will be degraded by Debye shielding. Even though many efforts use semiconductor materials directly as channels for biosensors, the electrical stability of semiconductors in the physiological environments has rarely been studied. In this work, an In2O3 nanolines FET device with high robustness in artificial physiological solution of phosphate buffered saline (PBS) was fabricated and used as a platform for biosensors without employing passivation on the sensing channel. The FET device demonstrated reproducibility with an average threshold voltage (V-TH) of 5.235 V and a standard deviation (SD) of 0.382 V. We tested the robustness of the In2O3 nanolines FET device in PBS solution and found that the device had a long-term electrical stability in PBS with more than 9 days' exposure. Finally, we demonstrated its applicability as a biosensor platform by testing the biosensing performance towards miR-21 targets after immobilizing the phosphonic acid terminated DNA probes. Since the surface immobilization of multiple bioreceptors is feasible, we demonstrate that the robust In2O3 FET device can be an excellent biosensor platform for biosensors.

DOI： 10.3390/mi12060642

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

A rapid and simple cancer detection method independent of cancer type is an important technology for cancer diagnosis. Although the expression profiles of biological molecules contained in cancer cell-derived extracellular vesicles (EVs) are considered candidates for discrimination indexes to identify any cancerous cells in the body, it takes a certain amount of time to examine these expression profiles. Here, we report the shape distributions of EVs suspended in a solution and the potential of these distributions as a discrimination index to discriminate cancer cells. Distribution analysis is achieved by low-aspect-ratio nanopore devices that enable us to rapidly analyze EV shapes individually in solution, and the present results reveal a dependence of EV shape distribution on the type of cells (cultured liver, breast, and colorectal cancer cells and cultured normal breast cells) secreting EVs. The findings in this study provide realizability and experimental basis for a simple method to discriminate several types of cancerous cells based on rapid analyses of EV shape distributions.

DOI： 10.1021/acs.analchem.1c00258

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

There are no accurate mass screening methods for early detection of central nervous system (CNS) tumors. Recently, liquid biopsy has received a lot of attention for less-invasive cancer screening. Unlike other cancers, CNS tumors require efforts to find biomarkers due to the blood-brain barrier, which restricts molecular exchange between the parenchyma and blood. Additionally, because a satisfactory way to collect urinary biomarkers is lacking, urine-based liquid biopsy has not been fully investigated despite the fact that it has some advantages compared to blood or cerebrospinal fluid-based biopsy. Here, we have developed a mass-producible and sterilizable nanowire-based device that can extract urinary microRNAs efficiently. Urinary microRNAs from patients with CNS tumors (n = 119) and noncancer individuals (n = 100) were analyzed using a microarray to yield comprehensive microRNA expression profiles. To clarify the origin of urinary microRNAs of patients with CNS tumors, glioblastoma organoids were generated. Glioblastoma organoid-derived differentially expressed microRNAs (DEMs) included 73.4% of the DEMs in urine of patients with parental tumors but included only 3.9% of those in urine of noncancer individuals, which suggested that many CNS tumor-derived microRNAs could be identified in urine directly. We constructed the diagnostic model based on the expression of the selected microRNAs and found that it was able to differentiate patients and noncancer individuals at a sensitivity and specificity of 100 and 97%, respectively, in an independent dataset. Our findings demonstrate that urinary microRNAs extracted with the nanowire device offer a well-fitted strategy for mass screening of CNS tumors.

DOI： 10.1021/acsami.1c01754

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Seeded crystal growths of nanostructures within confined spaces offer an interesting approach to design chemical reaction spaces with tailored inner surface properties. However, such crystal growth within confined spaces tends to be inherently difficult as the length increases as a result of confinement effects. Here, we demonstrate a space-confined seeded growth of ZnO nanowires within meter-long microtubes of 100 μm inner diameter with the aspect ratio of up to 10 000, which had been unattainable to previous methods of seeded crystal growths. ZnO nanowires could be grown via seeded hydrothermal crystal growth for relatively short microtubes below the length of 40 mm, while any ZnO nanostructures were not observable at all for longer microtubes above 60 mm with the aspect ratio of 600. Microstructural and mass spectrometric analysis revealed that a conventional seed layer formation using zinc acetate is unfeasible within the confined space of long microtubes as a result of the formation of detrimental residual Zn complex compounds. To overcome this space-confined issue, a flow-assisted seed layer formation is proposed. This flow-assisted method enables growth of spatially uniform ZnO nanowires via removing residual compounds even for 1 m long microtubes with the aspect ratio of up to 10 000. Finally, the applicably of ZnO-nanowire-decorated long microtubes for liquid-phase separations was demonstrated.

DOI： 10.1021/acsami.0c22709

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Detection of cell-free DNA (cfDNA) has an impact on DNA analysis in liquid biopsies. However, current strategies to detect cfDNA have limitations that should be overcome, such as having low sensitivity and requiring much time and a specialized instrument. Thus, non-invasive and rapid detection tools are needed for disease prevention and early-stage treatment. Here we developed a device having a microheater integrated with zinc oxide nanowires (microheater-ZnO-NWs) to detect target single-stranded DNAs (ssDNAs) based on DNA probe hybridization. We confirmed experimentally that our device realizedin-situannealed DNA probes by which we subsequently detected target ssDNAs. We envision that this device can be utilized for fundamental studies related to nanobiodevice-based DNA detection.

DOI： 10.1088/1361-6528/abef2c

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE RESEARCH  

Recent studies have shown that extracellular vesicles (EVs) can be utilized as appropriate and highly specific biomarkers in liquid biopsy for the diagnosis and prognosis of serious illness. However, there are few methods that can collect and isolate miRNA in EVs simply, quickly and efficiently using general equipment such as a normal centrifuge. In this paper, we developed an advanced glass membrane column (AGC) device incorporating a size-controlled macro-porous glass (MPG) membrane with a co-continuous structure to overcome the limitations of conventional EV collection and miRNA extraction from the EVs. The size of macro-pores in the MPG membrane could be accurately controlled by changing the heating temperature and time on the basis of spinodal decomposition of B2O3, Na2O, and SiO2 in phase separation. The AGC device with an MPG membrane could collect the EVs simply and quickly (<10 min) from cell culture supernatant, serum and urine. This AGC device could extract miRNA from the EVs captured in the MPG membrane with high efficiency when combined with a miRNA extraction solution. We suggest that the AGC device with an MPG membrane can be useful for the diagnosis and prognosis of serious illness using of EVs in various kinds of body fluids.

DOI： 10.1038/s41598-021-87986-2

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The surface cation composition of nanoscale metal oxides critically determines the properties of various functional chemical processes including inhomogeneous catalysts and molecular sensors. Here we employ a gradual modulation of cation composition on a ZnO/(Cu1-x Zn x )O heterostructured nanowire surface to study the effect of surface cation composition (Cu/Zn) on the adsorption and chemical transformation behaviors of volatile carbonyl compounds (nonanal: biomarker). Controlling cation diffusion at the ZnO(core)/CuO(shell) nanowire interface allows us to continuously manipulate the surface Cu/Zn ratio of ZnO/(Cu1-x Zn x )O heterostructured nanowires, while keeping the nanowire morphology. We found that surface exposed copper significantly suppresses the adsorption of nonanal, which is not consistent with our initial expectation since the Lewis acidity of Cu2+ is strong enough and comparable to that of Zn2+. In addition, an increase of the Cu/Zn ratio on the nanowire surface suppresses the aldol condensation reaction of nonanal. Surface spectroscopic analysis and theoretical simulations reveal that the nonanal molecules adsorbed at surface Cu2+ sites are not activated, and a coordination-saturated in-plane square geometry of surface Cu2+ is responsible for the observed weak molecular adsorption behaviors. This inactive surface Cu2+ well explains the mechanism of suppressed surface aldol condensation reactions by preventing the neighboring of activated nonanal molecules. We apply this tailored cation composition surface for electrical molecular sensing of nonanal and successfully demonstrate the improvements of durability and recovery time as a consequence of controlled surface molecular behaviors.

DOI： 10.1039/d1sc00729g

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Electrical molecular nanosensors require two conflicting surface characteristics, which are catalytic activity for molecular selectivity and thermal stability for long-term data collection. Here, we show that a simple surface treatment using strong acids creates two such conflicting surface properties of WO hydrate nanowires, which enhance the electrical molecular sensing of aldehydes (nonanal, a biomarker). Mass-spectrometric measurements reveal that the surface treatment using strong acids substantially promotes both the oxidization of nonanal and the desorption of products, nonanoic acid, from the surfaces at a temperature of 50 °C, which is lower than the 300 °C required for untreated surfaces. Spectroscopic and structural measurements combined with numerical simulations identify two different adsorption structures of carbonyl groups on the surface, where molecules directly bound to coordinatively unsaturated surface tungsten preferentially proceed to the catalytic oxidization reaction and the subsequent desorption process. Furthermore, we confirm the thermal durability (over 10 years) of the catalytic activity on acid-treated WO hydrate nanowire surfaces up to 300 °C, which enables us to demonstrate the long-term stable sensor operations with the sensitivity (4 orders of magnitude) remaining for years. 3 3

DOI： 10.1039/d0ta11287a

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Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

Measuring optically detected magnetic resonance (ODMR) of diamond nitrogen vacancy centers significantly depends on the photon detectors used. We study camera-based wide-field ODMR measurements to examine the performance in thermometry by comparing the results to those of the confocal-based ODMR detection. We show that the temperature sensitivity of the camera-based measurements can be as high as that of the confocal detection and that possible artifacts of the ODMR shift are produced owing to the complexity of the camera-based measurements. Although measurements from wide-field ODMR of nanodiamonds in living cells can provide temperature precisions consistent with those of confocal detection, the technique requires the integration of rapid ODMR measurement protocols for better precisions. Our results can aid the development of camera-based real-time large-area spin-based thermometry of living cells.

DOI： 10.1038/s41598-021-83285-y

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Cancer-derived circulating exosomes or nanoscale extracellular vesicles are emerging biomarkers for disease detection and treatment because of their cell-specific constituents and unique intercellular pathways. For efficient exosome isolation from bio-fluids, the design of high-affinity nanointerfaces is of great importance in the development of miniaturized systems for the collection of exosomes. Herein, we report peptide-functionalized nanowires as a biorecognition interface for the capture and release of cancer-derived exosomes within a microfluidic channel. Based on the amino-acid sequence of EWI-2 protein, a partial peptide that bound to the CD9 exosome marker and thus targeted cancer exosomes was screened. Linkage of the exosome-targeting peptide with a ZnO-binding sequence allowed one-step and reagent-free peptide modification of the ZnO nanowire array. As a result of peptide functionalization, the exosome-capturing ability of ZnO nanowires was significantly improved. Furthermore, the captured exosomes could be subsequently released from the nanowires under a neutral salt condition for downstream applications. This engineered surface that enhances the nanowires' efficiency in selective and controllable collection of cancer-derived exosomes provides an alternative foundation for developing microfluidic platforms for exosome-based diagnostics and therapeutics.

DOI： 10.1039/d0lc00899k

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

In this study, a facile, sensitive, and precise lab-on-a-chip electrophoretic method coupled with light-emitting diode induced fluorescence (LED-IF) detection was developed to assay three antiepileptic drugs, namely, vigabatrin, pregabalin, and gabapentin, in pharmaceutical formulations. The analytes were derivatised offline for the first time with fluorescine-5-isothiocyanate (FITC) to yield highly fluorescent derivatives with lambda(ex/em) of 490/520 nm. The FITC-labelled analytes were injected, separated, and quantitated by a microfluidic electropho-resis device using fluorescence detection. The labelled analytes were monitored using a blue LED-IF system. The separation conditions were significantly optimised adding specific concentrations of heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (HDM-beta-CD) and methylcellulose to the buffer solution (40 mM borate buffer). HDM-beta-CD acted as a selective host for the studied antiepileptic drugs, rendering a high separation efficiency. Methyl-cellulose was used as an efficient dynamic coating polymer to prevent the labelled drugs from being adsorbed on the inner surfaces of the poly (methylmethacrylate) microchannels. A laboratory-prepared ternary mixture of the three antiepileptic drugs was separated within 100 s with acceptable resolution between all the three analytes (R-s > 3) and a high number of theoretical plates (N) for each analyte (N approximate to 10(6) plates/m). The sensitivity of the method was enhanced approximately 80-fold by stacking to yield a detection limit below 0.6 ng mL(-1) in the concentration range of 2.0-200.0 ng mL(-1). The method was successfully validated for analysing the studied drugs in their pharmaceutical formulations. (c) 2020 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.saa.2020.119021

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Atomic layer deposition (ALD) is capable of providing an ultrathin layer on high-aspect ratio structures with good conformality and tunable film properties. In this research, we modified the surface of ZnO nanowires through ALD for the fabrication of a ZnO/SiO2 (core/shell) nanowire microfluidic device which we utilized for the capture of CpG-rich single-stranded DNAs (ssDNA). Structural changes of the nanowires while varying the number of ALD cycles were evaluated by statistical analysis and their relationship with the capture efficiency was investigated. We hypothesized that finding the optimum number of ALD cycles would be crucial to ensure adequate coating for successful tuning to the desired surface properties, besides promoting a sufficient trapping region with optimal spacing size for capturing the ssDNAs as the biomolecules traverse through the dispersed nanowires. Using the optimal condition, we achieved high capture efficiency of ssDNAs (86.7%) which showed good potential to be further extended for the analysis of CpG sites in cancer-related genes. This finding is beneficial to the future design of core/shell nanowires for capturing ssDNAs in biomedical applications.

DOI： 10.1039/d0ay02138e

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.0c04353

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Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER  

A green chiral lab-on-a-chip cyclodextrin-based microchip electrophoretic method was developed for enantioseparation of baclofen (BCN) and phenylalanine (Phe) enantiomers for the first time. All BCN and Phe enantiomers were offline labeled with 4-fluoro-7-nitrobenzofurazan (NBD-F) or fluorescein-5-isothiocyanate (FITC) fluorogenic reagents prior to microfluidic injection in a dynamically coated polymethylmethacrylate microchip. The enantioseparation was performed using borate buffer solution (50 mM; pH 9.5) containing a dynamic coating polymer (methylcellulose) and a chiral selector of cyclodextrin (CD) family as the background electrolyte. The combination of sieving properties of methylcellulose polymer and inclusion complex formation properties of the cyclodextrins rendered a novel green pseudo-stationary phase for the microfluidic chiral separation of the studied enantiomers in short separation time. Seven CD chiral selectors were investigated in our study to illustrate the proposed enantioseparation mechanism in the dynamically coated microfluidic channels. The results indicated that use of a modified cyclodextrin, heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (HDM-beta-CD), resulted in extra interactions with the analytes of interest, leading to extra resolution with high number of theoretical plates. Therefore, HDM-beta-CD was able to separate the NBD-labeled and FITC-labeled enantiomers of BCN and Phe within short analytical time. Sensitivity problem of microchip electrophoresis was overcome by application of field-enhanced injection stacking which improved sensitivity to a higher extent by online pre concentration of the labeled enantiomers in the microfluidic channels. The method was fully validated and successfully applied for the assay of BCN enantiomers and Phe enantiomers in their pure racemic mixtures. Moreover, the developed method was applied for precise analysis of BCN enantiomers in pharmaceutical formulations and in biological samples. The extraction recovery values of BCN enantiomers in biological samples were 87.5% and %RSD < 7.0.

DOI： 10.1016/j.microc.2020.105770

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Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Organ Preservation and Biology  

<p><i>In vivo</i> imaging technology can detect and diagnose almost all of transplanted cells remains unestablished. In order to enhance the safety and treatment effect of regenerative medicine, it is necessary to understand where transplanted cells accumulate in the tissue and how the accumulated cells behave in tissues and organs at a cell level. In this study, we challenged the innovative diagnosis of transplanted islet cells in the liver of mice by advanced technologies such as fluorescence imaging using “quantum dots (QDs)” and whole tissue clearing using “clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC)”. After transplantation of islet cells labeled with QDs800 into the living body of the nude mice through portal vein, it was confirmed that the transplanted islet cells were mainly accumulated in the liver of the mice after 10 min. of transplantation using <i>in vivo</i> imaging system. In addition, we now examine the spatiotemporal distribution of transplanted islet cells at the single cell level by organ clearing and 3D imaging of organs using light sheet fluorescence microscopy.</p>

DOI： 10.11378/organbio.28.136

CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM  

Liquid biopsy is a method that is expected to be able to detect and track the cancers using blood, urine, saliva and other body fluids. The advantages of liquid biopsy are that it is extremely minimally invasive compared to tissue biopsies, and that it is easy to perform the repeated and frequent tests that are necessary for long-term tracking. Recently, extracellular vesicles （EVs） have been added to the list of biological materials to be analyzed by liquid biopsy. In this paper, we introduce the comprehensive analysis of microRNAs contained in EVs in urine using nanowire devices and AI, and its application to cancer detection.

DOI： 10.2745/dds.36.124

Scopus

CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Macromolecules  

To investigate the effect of the network structure on the mechanical properties of a polymer network formed from a certain polymer, we should prepare polymer networks with clearly different network structures made of the same polymer and compare the mechanical properties of these polymer networks. If a living radical polymerization method is applied to the same monomer constituting the polymer network with a nonuniform network structure obtained by conventional free-radical polymerization, it is possible to obtain a polymer network with a uniform network structure in which the molecular weights of the polymer chains bonded to the cross-linking points are uniform and the number of chains bonded to the cross-linking points is constant. In this study, we worked on the synthesis of a polymer network with a uniform network structure by combining two different types of star-shaped polymer synthesis methods using living radical polymerization, i.e., the core-first method and the linking method. In the core-first method, it was possible to synthesize a star-shaped polymer with a narrow molecular weight distribution in a state with a molecular weight corresponding to the charging ratio of the initiator with four initial groups and the monomer. We confirmed that the polymer network obtained by binding the star-shaped polymers by the linking method had a uniform structure, even when swollen with a good solvent or dried, from small-angle X-ray scattering. Depending on the molecular weight of the star-shaped polymer obtained by the core-first method and the amount of the cross-linking agent added for the linking method, the mesh size of the network could be changed while having a uniform network structure. The dried polymer network with uniform network structures exhibited significantly higher values of fracture extensibility and energy than those with nonuniform network structures via conventional free-radical polymerization, when compared at the same monomer and cross-linker concentration.

DOI： 10.1021/acs.macromol.1c01680

Scopus

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

The variability of bioparticles remains a key barrier to realizing the competent potential of nanoscale detection into a digital diagnosis of an extraneous object that causes an infectious disease. Here, we report label-free virus identification based on machine-learning classification. Single virus particles were detected using nanopores, and resistive-pulse waveforms were analyzed multilaterally using artificial intelligence. In the discrimination, over 99% accuracy for five different virus species was demonstrated. This advance is accessed through the classification of virus-derived ionic current signal patterns reflecting their intrinsic physical properties in a high-dimensional feature space. Moreover, consideration of viral similarity based on the accuracies indicates the contributing factors in the recognitions. The present findings offer the prospect of a novel surveillance system applicable to detection of multiple viruses including new strains.

DOI： 10.1021/acssensors.0c01564

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.0c03959

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PubMed

Language：English   Publishing type：Research paper (international conference proceedings)  

© 2020 CBMS-0001 Toward tracking lifelong exposure history of particulate matters (PMs) for understanding its disease risk, we realized a surfactant-assisted ionic current sensing for analyzing the size and concentration of hydrophobic PMs. Previously, we reported a PM sensor via water film-based collection and micropore-employed ionic current sensing at MicroTAS 2018 [1]. However, an analysis on PM number concentration has not achieved due to a difficulty in sensing hydrophobic PMs. Here, the hydrophobic PMs were detected with the aid of sodium dodecyl sulfate (SDS) and information on PM size and number concentration was obtained.

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

© 2020 CBMS-0001 Lifelong exposure history (exposome) of particulate matters (PMs) is essential for understanding environmentally induced health risk, however, diversities in PM size, shape and components are a technical barrier to track the exposome. Previously, we reported a PM sensor utilizing water film-based collection and microfluidics-employed ionic current measurement at MicroTAS 2018 [1], which was only applied to analyze non-soluble PMs. Herein, we realized a potentiometry-based methodology for sensing multiple ion components derived from water-soluble PMs via arrayed ion-selective electrodes (ISEs). NO3-, NH3+, and Na+ ions extracted from a real PM sample were simultaneously detected and analyzing their contents was achieved.

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Language：English  

Publishing type：Research paper (international conference proceedings)   Publisher：MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences  

Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)  

Recent studies on nanopillar arrays, one type of nanofluidic device, have demonstrated various tools for bioanalysis. When carrying out nanopillar array-based separation, it is indispensable to observe biomolecules, such as DNA, proteins, and extracellular vesicles, that have fluorescence labeling; however, fluorescence labeling influences the biomolecular characteristics. Here, we have proposed label-free monitoring of biomolecule separation by using diffracted light derived from the nanopillar array that was fabricated inside a microchannel by combining laser interference lithography with general photolithography techniques. Using an electrophoresis approach, we demonstrated that our diffraction-based label-free method possessed high sensor initialization ability, and the nanopillar array device successfully monitored DNA separation without labeling bias. Results obtained using our label-free monitoring of DNA separation confirmed, for the first time, that the molecular dynamics of DNA molecules in the nanopillar array were changed in the presence or absence of fluorescent labeling. The presented concept will provide a useful tool for nonbiased monitoring of label-free biomolecule analysis in nanofluidic channels.

DOI： 10.1021/acsanm.0c01600

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Ammonia is a well-known additive to promote crystal growth in hydrothermal synthesis of ZnO nanowires. Although the effect of ammonia on the nanowire growth has been intensively investigated, its influence on the seed layer, which governs the initial nanowire growth, is rarely discussed. Here, we demonstrate that ammonia strongly affects the seed layer as well as the following nanowire growth. On increasing the ammonia concentration, the nanowire density first increases and then decreases, while the nanowire growth rate keeps increasing. Experimental results and thermodynamic calculations of the initial growth process reveal that the transformation of the seed layer induced by ammonia prior to nucleation critically determines the nanowire density and thus also influences the following nanowire growth. Present results highlight the critical importance of discussing the variation of seed layers in ammonia-involved hydrothermal synthesis and suggest a novel seed engineering approach for tailoring the ZnO nanowire growth.

DOI： 10.1021/acs.jpcc.0c05490

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGERNATURE  

Tailoring the elemental doping of inorganic nanowires remains an important challenge due to complex dopant incorporation pathways. Here we report that the face-selectivity of tungstate ions controls growth direction and dopant incorporation of hydrothermal zinc oxide nanowires. The introduction of tungstate ions on nanowire surface during synthesis unexpectedly enhances nucleation at sidewall <mml:mfenced close="}" open="{">101<mml:mo><overbar></mml:mover>0</mml:mfenced> planes, while dopant incorporation occurs only on (0001) planes. This conflicting face-selective behavior leads to inhomogeneous dopant distribution. Density functional theory calculations reveal that the face-selective behavior can be interpreted in terms of the effect of coordination structure of the tungstate ions on each zinc oxide crystal plane. In addition, we demonstrate a rational strategy to control the morphology and the elemental doping of tungsten-doped zinc oxide nanowires. Controlling the growth processes of nanowires is vital for tailoring their properties. Here, the presence of tungstate ions on specific surface planes of zinc oxide nanowires causes nanowire growth and chemical doping along specific crystal planes.

DOI： 10.1038/s43246-020-00063-5

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Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

There are growing interests in mechanical rupture-based antibacterial surfaces with nanostructures that have little toxicity to cells around the surfaces; however, current surfaces are fabricated via top-down nanotechnologies, which presents difficulties to apply for bio-surfaces with hierarchal three-dimensional structures. Herein, we developed ZnO/SiO2 nanowire structures by using bottom-up approaches and demonstrated to show mechanical rupture-based antibacterial activity and compatibility with human cells. When Escherichia coli were cultured on the surface for 24 h, over 99% of the bacteria were inactivated, while more than 80% of HeLa cells that were cultured on the surface for 24 h were still alive. This is the first demonstration of mechanical rupture-based bacterial rupture via the hydrothermally synthesized nanowire structures with antibacterial activity and cell compatibility.

DOI： 10.3390/mi11060610

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijpharm.2020.119338

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.0c01417

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Toxicology  

<p>We have devolved nanobiodevices, quantum technology, and AI for biomedical applications and healthcare, including single cancer cell diagnosis for cancer metastasis, circulating tumour cell (CTC) detection by microfluidic devices, nanopillar devices for ultrafast analysis of genomic DNA and microRNA, nanopore devices for single DNA sequencing, nanowire devices for exosome analysis, single-molecular epigenetic analysis, AI-powered nano-IoT sensors, quantum switching intra vital imaging of iPS cells and stem cells, and quantum technology-based cancer theranostics. </p>

DOI： 10.14869/toxpt.47.1.0_S25-2

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Intracellular thermometry techniques play an important role in elucidating the relationship between the intracellular temperature and stem cell functions. However, there have been few reports on thermometry techniques that can detect the intracellular temperature of cells during several days of incubation. In this study, we developed a novel quantum thermometric sensing and analysis system (QTAS) using fluorescent nanodiamonds (FNDs). FNDs could label adipose tissue-derived stem cells (ASCs) at high efficiency with 24 h of incubation, and no cytotoxicity was observed in ASCs labeled with less than 500 mg mL(-1) of FNDs. The peak of FNDs was confirmed at approximately 2.87 GHz with the characteristic fluorescence spectra of NV centers that could be optically detected (optically detected magnetic resonance [ODMR]). The ODMR peak clearly shifted to the high-frequency side as the temperature decreased and gave a mean temperature dependence of -(77.6 +/- 11.0) kHz degrees C-1, thus the intracellular temperature of living ASCs during several days of culturing could be precisely measured using the QTAS. Moreover, the intracellular temperature was found to influence the production of growth factors and the degree of differentiation into adipocytes and osteocytes. These data suggest that the QTAS can be used to investigate the relationship between intracellular temperature and cellular functions.

DOI： 10.1039/d0na00146e

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Scopus

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c9nr10565d

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/cells9041019

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2116/analsci.20N002

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1089/ten.TEC.2020.0029

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Copyright © 2020 American Chemical Society. Multinary semiconductor quantum dots (QDs) that have less toxicity and show near-infrared light responsivity have attracted much attention for in vivo bioimaging. In this study, we controlled the optical properties of Ag-In-Se QDs by modulating the nonstoichiometry and the degree of Ga3+ doping. Precise tuning of the Ag/In ratio of Ag-In-Se QDs enabled a sharp band-edge emission to emerge without broad defect-site emission. Ga3+ doping into Ag-In-Se (AIGSe) QDs enlarged their energy gap, resulting in a blue shift of the band-edge PL peak from from 890 to 630 nm. The band-edge PL intensity was remarkably enlarged by surface coating with a thin GaSx shell followed by treatment with trioctylphosphine, the highest PL yield being 38% for the PL peak at 800 nm. Thus-obtained QDs were successfully used as near-IR PL probes for three-dimensional in vivo bioimaging in which the wavelengths of excitation and detection lights could be selected in the first biological window, and then the signals were clearly detected from AIGSe@GaSx core-shell QDs injected into biological tissues by ca. 5 mm in depth.

DOI： 10.1021/acsanm.9b02608

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2116/analsci.20R001

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.9b03939

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Small cell lung cancer (SCLC) has a poor prognosis, and its treatment options are limited. Delta-like protein 3 (DLL3) is expressed specifically in SCLC and is considered a promising therapeutic target for patients with this disease. Rovalpituzumab tesirine (Rova-T) was the first antibody-drug conjugate targeting DLL3. Although Rova-T development was unfortunately terminated, DLL3 remains an ideal target for SCLC. Near infrared photoimmunotherapy (NIR-PIT) is a new form of cancer treatment that employs an antibody-photosensitiser conjugate followed by NIR light exposure and damage target cells specifically. In this study, we demonstrate DLL3-targeted NIR-PIT to develop a novel molecularly targeted treatment for SCLC. METHODS: The anti-DLL3 monoclonal antibody rovalpituzumab was conjugated to an IR700 photosensitiser (termed 'rova-IR700'). SCLC cells overexpressing DLL3 as well as non-DLL3-expressing controls were incubated with rova-IR700 and then exposed to NIR-light. Next, mice with SCLC xenografts were injected with rova-IR700 and irradiated with NIR-light. FINDINGS: DLL3-overexpressing cells underwent immediate destruction upon NIR-light exposure, whereas the control cells remained intact. The xenograft in mice treated with rova-IR700 and NIR-light shrank markedly, whereas neither rova-IR700 injection nor NIR-light irradiation alone affected tumour size. INTERPRETATION: Our data suggest that targeting of DLL3 using NIR-PIT could be a novel and promising treatment for SCLC. FUNDING: Research supported by grants from the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, JSPS), Medical Research Encouragement Prize of The Japan Medical Association, The Nitto Foundation, Kanae Foundation for the Promotion of Medical Science.

DOI： 10.1016/j.ebiom.2020.102632

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1089/scd.2019.0221

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Organ Preservation and Biology  

<p>It has become clear that temperature plays a major role in many life phenomena. However, little is known about the intracellular temperature, and the relationship between regenerative function and intracellular temperature of stem cells. In this study, fluorescent nanodiamond (FND) that can be applied as an excellent quantum sensor was used for stem cell labeling. Then, the relationship between the regenerative function of stem cells and the intracellular temperature of stem cells was evaluated by a sensing the optically detected magnetic resonance (ODMR) activity of NV centers in FNDs. FNDs could label adipose tissue-derived stem cells (ASCs) at high efficiency with 24 h incubation, and no cytotoxicity was observed in ASCs labeled with less than 500 µg/mL of FNDs. The ODMR of NV centers in FNDs was confirmed at approximately 2.87 GHz with a characteristic fluorescence spectrum, and the intracellular temperature of living ASCs during several days of culturing could be precisely measured. Moreover, the intracellular temperature was found to influence the production of growth factors and the degree of differentiation into adipocytes and osteocytes. These data suggest that NV centers in FNDs can be used to investigate the relationship between intracellular temperature and cellular functions.</p>

DOI： 10.11378/organbio.27.185

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Detecting molecular targets in specimens from patients with lung cancer is essential for targeted therapy. Recently, we developed a highly sensitive, rapid-detection device (an immuno-wall device) that utilizes photoreactive polyvinyl alcohol immobilized with antibodies against a target protein via a streptavidin-biotin interaction. To evaluate its performance, we assayed epidermal growth factor receptor (EGFR) mutations, such as E746_A750 deletion in exon 19 or L858R substitution in exon 21, both of which are common in non-small cell lung cancer and important predictors of the treatment efficacy of EGFR tyrosine kinase inhibitors. The results showed that in 20-min assays, the devices detected as few as 1% (E746_A750 deletion) and 0.1% (L858R substitution) of mutant cells. Subsequent evaluation of detection of the mutations in surgically resected lung cancer specimens from patients with or without EGFR mutations and previously diagnosed using commercially available, clinically approved genotyping assays revealed diagnostic sensitivities of the immuno-wall device for E746_A750 deletion and L858R substitution of 85.7% and 87.5%, respectively, with specificities of 100% for both mutations. These results suggest that the immuno-wall device represents a good candidate next-generation diagnostic tool, especially for screening of EGFR mutations.

DOI： 10.1371/journal.pone.0241422

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Analytical Chemistry  

<p>Fine particulate matter sized 2.5 μm or less, referred to as PM_2.5, causes serious air pollution in urban cities and is responsible for several health problems, such as respiratory disease and asthma in urban populations. Although seasonal Asian dust, called Kosa (∼ 5 μm), has been extensively studied for over decades, and has been shown to be an allergen in Japan, the influence of PM_2.5 on human health has remained unclear due to the intrinsic chemical and biological complexity of isolating variables for study. In this study, PM_2.5 was collected at Ito Campus in Kyushu University, Fukuoka, located in extreme western Japan and its physical and biological characteristics were analyzed. The presence of bacteria, <i>Firmicutes</i> genus <i>Bacillus, Lysinibacillus, Paenibacillus, Gracilibacillus</i>, and <i>Solibacillus</i> in the collected PM_2.5 sample was confirmed by culturing and conducting DNA sequencing of their 16S rRNA gene.</p>

DOI： 10.2116/bunsekikagaku.69.741

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.nanolett.9b04367

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.9b02818

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DOI： 10.1021/acsomega.9b02788

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-019-50641-y

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Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1167/iovs.19-27788

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c9an00480g

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acsnano.9b03259

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.analchem.8b05538

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acsomega.9b00945

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acs.nanolett.8b05180

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Language：English   Publishing type：Research paper (international conference proceedings)  

© 2018 IEEE. Toward evaluating health risk of particulate matter with size less than or equal to 2.5 μm (PM2.5), we propose a methodology for realizing the PM2.5 analysis in liquid phase via water film-based collection and microfluidics-based electrical detection. We reported last year that a hydrophilic nanowire surface was utilized in the collection for formation of a water film, which enabled continuous collection of air-floating PM2.5 into liquid phase and followed-by detection. As advanced results, the collected PM2.5 was successfully detected and analyzed via ion current sensing using a micropore. We believe proposed PM2.5 analysis methodology in liquid phase would allow to realize health risk evaluation and reduce health damage.

DOI： 10.1109/NANOMED.2018.8641523

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acsnano.8b08959

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c8lc01105b

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c9ra02282a

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/978-981-13-6229-3_10

Web of Science

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Organ Preservation and Biology  

<p><i>In vivo</i> imaging technology can detect and diagnose a total of transplanted stem cells remains unestablished. In order to enhance the safety and treatment effect of regenerative medicine, it is necessary to understand where transplanted stem cells accumulate in the tissue and how accumulated cells behave in the tissue at a single cell level. In this study, we challenged the innovative diagnosis of transplanted stem cells in acute liver failure model mice by quantum dots (QDs) fluorescence imaging and whole tissue clearing technologies.</p><p>After transplantation of stem cells labeled with QDs655 into the living body of the acute liver failure model mice through tail vein, it was confirmed that the transplanted stem cells were mainly accumulated in the lung and liver of the mice using <i>in vivo</i> imaging system. In addition, we succeeded in revealing the spatiotemporal distribution of transplanted stem cells at the single cell level by organ clearing and 3D imaging of organs using light sheet fluorescence microscopy.</p>

DOI： 10.11378/organbio.26.199

CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：公益社団法人 日本生体医工学会  

<p>幹細胞移植は幹細胞をそのまま、あるいは前駆細胞に分化させた状態で血流に乗せて移植する治療法であり、幹細胞を用いた組織や臓器の再構築が未だ困難とされている疾病に対して有効な治療法であるとして近年注目を集めている。幹細胞移植の実現に向けては、安全性が十分に確保されており、尚且つ治療効果が大きい移植プロトコールを確立する必要があり、この課題の解決に向けて、移植幹細胞の体内動態や生着部位を高感度にイメージングし、どのように治療効果を発揮しているかを解明する必要がある。しかし、これまで生体内のすべての移植幹細胞を網羅的にイメージング診断できる技術は確立されていない。臓器や組織は光を吸収・散乱する様々な物質から構成されており、光の透過性が極めて低いため、二光子励起顕微鏡などを用いても表面上のしかも限られた視野での観察に留まっているのが現状である。そこで我々は、臓器の効率的な透明化が可能な技術に注目し量子ドットを用いた幹細胞蛍光イメージング技術と融合することで、急性肝不全モデルマウスにおける移植幹細胞の網羅的、且つ単一細胞レベルの解像度でのイメージングを可能にする革新的診断技術の確立に取り組んだ。</p>

DOI： 10.11239/jsmbe.annual57.s177_1

CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：公益社団法人 日本生体医工学会  

<p>幹細胞による再生治療メカニズム解明は、再生医療の更なる安全性、治療効果向上において極めて重要である。幹細胞は自己複製能と多分化能を持つ特殊な細胞であり、障害部位への特異的な集積能力や再生因子産性能を持つことから患者に移植することで治療効果を発揮することが知られている。更に、近年では幹細胞から放出されるエクソソームも同様に治療効果を持つことがわかっており、新規治療ツールとして注目され始めている。しかし、エクソソームの詳細な生体内挙動及び細胞間移動等について解析できる技術が乏しく、再生機能の役割については未だ未解明のままである。本研究では、エクソソームを生体内で高感度に検出できる技術の確立を目指した。最先端量子ナノ材料である量子ドットをグルコース修飾することで、もともと細胞が持つグルコーストランスポーターを通して細胞内に導入することに成功した。また、グルコーストランスポーターを持つとされるエクソソームにおいても同様に内部への導入が確認された。エクソソームの内部に導入することで、膜上に蛍光色素を付着させる従来法に比べてより安定で高感度のラベル化に成功した。</p>

DOI： 10.11239/jsmbe.annual57.s81_1

CiNii Research

Language：English   Publishing type：Research paper (international conference proceedings)  

© 2019 CBMS-0001. Peptides optimally binding to solid surfaces are a promising candidate for adding bio-affinity, however, their binding states are not fully revealed. Herein, we realized a methodology for analyzing peptide adsorption states via employing nanowires and infrared (IR) p-polarized multiple-angle incidence resolution spectrometry (pMAIRS). Our methodology enabled to provide large crystalline surface for peptide adsorption, and enhance signal intensities. We found that a modelled peptide had different adsorption states among crystal axes. Analyzing peptide adsorption states can pave the way for controlling adsorbed states, and moreover, using full potentials of peptide.

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

© 2019 CBMS-0001. Analyzing microRNAs in our body allowed us to investigate our various vital in Here [1], our aim is that discovering additional vital information based on microRNAs from saliva samples. MicroRNAs in body fluids are known to obtain higher stability in body fluids via encapsulation in extracellular vesicles with over 40-nm diameter [2]. To capture the vesicles, we conceived an idea to use nanocellulose with several 10- to several 100-nm pore sizes. The nanocellulose made it possible to extract over 1000 species of microRNAs from 10 µL saliva within 20 s, compared to ultracentrifugation, which required over 180 min and 10 µL saliva to extract around 600 species of microRNAs.

Scopus

Language：Japanese  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English  

Publishing type：Research paper (scientific journal)   Publisher：23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019  

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Publishing type：Research paper (scientific journal)   Publisher：23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019  

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Publishing type：Research paper (scientific journal)   Publisher：23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019  

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Publishing type：Research paper (scientific journal)   Publisher：23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019  

Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   Publisher：23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019  

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

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CiNii Research

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CiNii Research

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CiNii Research

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Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c8lc00438b

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/annonc/mdy441.027

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/adbi.201800137

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jss.2018.01.016

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c8nj00829a

Web of Science

Language：English   Publishing type：Research paper (international conference proceedings)  

© 2018 The Japan Society of Applied Physics. A fluoropolymer membrane filter with through-holes was fabricated by photolithographic patterning and the dry etching method. 380,000 highly packed through-holes, each with a diameter of 7 µm were able to cover a whole area with a diameter of 13 mm. Ethylene tetrafluoroethylene (ETFE) was used as the membrane, which was suitable for the fluorescence detection of rare cells such as circulating tumor cells (CTCs) in human blood. The device fabrication for the size based capture of rare cells in blood such as CTCs is realized in this study.

DOI： 10.7567/JJAP.57.06JF03

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ymgmr.2018.01.005

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1177/2155179017733152

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.snb.2018.01.079

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Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC ANALYTICAL CHEMISTRY  

Quantum dots (QDs) have excellent fluorescence properties in comparison to traditional fluorescence probes. Thus, the optical application of QDs is rapidly expanding to each field of analytical chemistry. In this review paper, we reviewed the application of QDs to regenerative medicine, especially stem cell transplantation therapy. The labeling of stem cells using QDs composed of semiconductor materials in combination with a chemical substance, poly-cationic liposome and cell penetrating peptide is reported. In addition, the influence of QD labeling on the pluripotency of stem cells is also reported. Finally, the in vivo imaging of transplanted stem cells in mice by QDs emitting fluorescence in the near-infrared region, which can be detected by in vivo fluorescence imaging systems such as IVIS and SAI-1000, is described. The future prospects for stem cell imaging technology by QDs are also discussed.

DOI： 10.2116/analsci.17R005

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-018-24563-0

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Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/mi9040180

Web of Science

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)蕗書房  

CiNii Books

J-GLOBAL

Language：Japanese   Publishing type：Research paper (scientific journal)  

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1246/cl.171139

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/acssensors.8b00045

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.7567/JJAP.57.037001

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.4028/www.scientific.net/NHC.19.55

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CiNii Research

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Language：English   Publishing type：Research paper (scientific journal)  

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Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Analytical Chemistry  

© 2018 The Japan Society for Analytical Chemistry. We have demonstrated a PM 2.5 analysis method that adds information on the number concentration and size by using microfluidic-based ionic current sensing with a bridge circuit. The bridge circuit allows for suppression of the background current and the detection of small PM 2.5 particles, even if a relatively large micropore is used. This is the first demonstration of the detection of PM 2.5 particles via ionic current sensing; our method enables analyses of both the number concentration and size.

DOI： 10.2116/analsci.18C018

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PubMed

CiNii Research

Language：English   Publishing type：Research paper (international conference proceedings)  

Copyright© (2018) by Chemical and Biological Microsystems Society.All rights reserved. In this study, we have developed ionic current detection device that can discriminate cells by measurement of cell deformability for detecting circulating tumor cells (CTC). We successfully discriminated CTC model from leukocyte model without any fluorescent labels by using the device. Moreover, we could detect relatively small CTCs compared to blood cells, which are difficult to detect by conventional filter devices. This device is expected as a new cancer diagnostic device that is simple and highly sensitive.

Scopus

Publishing type：Research paper (scientific journal)   Publisher：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018  

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

Copyright© (2018) by Chemical and Biological Microsystems Society.All rights reserved. Toward evaluation of health risk of particulate matter with size less than or equal to 2.5 µm (PM2.5), we propose a methodology for realizing the PM2.5 analysis in liquid phase via water film-based collection and microfluidics-based electrical detection. A hydrophilic nanowire surface was utilized in the collection for forming a water film, which enabled continuous collection of air-floating PM2.5 into liquid phase and followed-by detection. The collected PM2.5 was electrically detected and analyzed via ionic current sensing with a micropore. We believe proposed PM2.5 analysis methodology in liquid phase would allow to realize health risk evaluation and reduce health damage.

Scopus

Publishing type：Research paper (international conference proceedings)   Publisher：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018  

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved. We present a study of genomic profiling for circulating tumor cells (CTCs) using a blood microfiltration system. DNA amplification of CTCs was performed with a microfilter for single cancer cells in a clinical setting. This strategy was successfully used to detect the driver mutations in epidermal growth factor (EGF) receptor oncogenes by quantitative PCR and characterize the dosing effect of molecularly targeted drug for lung cancer.

Scopus

Publishing type：Research paper (international conference proceedings)   Publisher：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018  

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved. Detecting of cell-free circulating methylated DNA could be a promising method for early diagnosis of cancer. Here we have developed the microheater - zinc oxide nanowires (ZnO-NWs) structures embedded in the microchannel device for capturing DNA via electrostatic interaction. We found that 60% of DNA could be captured on ZnO-NWs. Additionally, the microheater, which constantly enables to generate heat, can denature double stranded DNA (dsDNA) to single stranded DNA (ssDNA). Finally, ICON Probe, which is an artificial ssDNA probe for DNA methylation, was introduced inside a device to bind to ssDNA for DNA methylation detection.

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved. We present a study of centrifugal filtration device toward easy-to-use approach of non-invasive liquid biopsy for cancer diagnosis by cell-derived nanoscale vesicles (exosomes). A phase-dispersed glass filter having nanoporous structure was embedded into a spin column to trap exosomes with small centrifuge. This device enabled over 90% exosome isolation from biological samples within 10 minutes.

Scopus

Publishing type：Research paper (international conference proceedings)   Publisher：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018  

Scopus

Publishing type：Research paper (international conference proceedings)   Publisher：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018  

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)  

Copyright © (2018) by Chemical and Biological Microsystems Society. All rights reserved. Molecular recognition methods such as those found in antigen-antibody reactions are attracting attention. We demonstrated more selective molecular recognition through focusing on not only intermolecular interaction but also the shape of the molecules. Here, we fabricated molecular shapes of aniline on the titanium oxide thin film on the core-shell structure of zinc oxide/titanium oxide nanowires, and recognized aniline, selectively, using the aniline molecular shaped nanowires.

Scopus

Publishing type：Research paper (international conference proceedings)   Publisher：22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018  

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-017-17443-6

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1126/sciadv.1701133

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DOI： 10.1371/journal.pone.0187962

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Language：English   Publishing type：Research paper (other academic)  

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DOI： 10.1016/j.snb.2017.04.150

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/jacs.7b06440

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-017-09115-2

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-017-09115-2

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Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ccr3.1056

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.chroma.2017.04.049

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 0.2116/analsci.33.735

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jbm.a.36105

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC ANALYTICAL CHEMISTRY  

Here, we developed a device integrated with a nanochannel and nanostructures to slow DNA translocation velocity. We found that translocation velocity of a single DNA molecule inside a nanochannel was decreased by pre-elongating it using some nanostructures, such as a shallow channel or nanopillars. This decrease of the translocation velocity was associated with the DNA mobility change, which is an intrinsic parameter of DNA molecules and unaffected by an electric field.

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/srep43877

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/srep43877

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 0.2116/analsci.33.143

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC ANALYTICAL CHEMISTRY  

The steady state and time-resolved photoluminescence quenching of streptavidin modified CdSe/ZnS quantum dots (QDs) instigated by biotin-peptide-BHQ-1 (biotin-pep-BHQ-1) molecule was investigated. Here, we have achieved an efficient photoluminescence (PL) quenching of QDs with the conjugation of dark quencher (black hole quencher-BHQ) molecules intermediated with the GPLGVRGK peptide. The luminescence of streptavidin-QDs585 was decreased upon titration with a nano molar concentration of the biotin-GPLGVRGK-BHQ-1 molecule. It has been suggested that the decrease of QDs PL occurred through a Forster resonance energy transfer (FRET) mechanism from the analysis of steady state photoluminescence intensity measurements as well as time resolved lifetime measurements of streptavidin-QDs and QDs(pep-BHQ-1)(n) conjugates. The sequence of intermediate peptide GPLG down arrow VRGK can act as a target material for matrix metalloproteinases-2 (MMP-2) produced by cancer cells at its Gly and Val region, shown by the down-headed arrow. Interestingly, here the reported self-assembled QDs-(pep-BHQ-1)(n) conjugates could detect the presence MMP-2 at a detection limit of 1 ng/mL with a clear luminescence recovery.

DOI： 10.2116/analsci.33.137

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC ANALYTICAL CHEMISTRY  

We investigated the transduction function of a cationic dextran hydroxypropyltrimethyl ammonium chloride-coated magnetic iron oxide nanoparticle (TMADM-03) for transducing quantum dots (QDs) into adipose tissue-derived stem cells (ASCs). As a result, the fluorescence intensity of ASCs labeled with QDs using TMADM-03 was much higher than that of QDs only labeling. These data suggest that TMADM-03 can be useful as a transduction agent for QDs in stem-cell imaging.

Web of Science

Language：English  

DOI： 10.1021/acs.analchem.6b04763

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

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DOI： 10.1038/srep40047

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/srep40047

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Authorship：Lead author   Language：Japanese  

DOI： 10.2745/dds.32.8

Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Analytical Chemistry  

Here, we report the effect of DNA methylation on the velocity of DNA translocation through a nanochannel, as determined by measuring differences in translocation velocities between methylated and non-methylated DNA molecules. We found that the velocity of translocation of methylated DNA was faster than that of non-methylated DNA, which we attributed to variation in the coefficients of diffusion and friction with the nanochannel wall, due to the increased molecular weight and stiffness, respectively, of methylated DNA.

DOI： 10.2116/analsci.33.727

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PubMed

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

We investigated the transduction function of a cationic dextran hydroxypropyltrimethyl ammonium chloride-coated magnetic iron oxide nanoparticle (TMADM-03) for transducing quantum dots (QDs) into adipose tissue-derived stem cells (ASCs). As a result, the fluorescence intensity of ASCs labeled with QDs using TMADM-03 was much higher than that of QDs only labeling. These data suggest that TMADM-03 can be useful as a transduction agent for QDs in stem-cell imaging.

DOI： 10.2116/analsci.33.143

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Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/978-1-4939-6734-6_4

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/978-1-4939-6734-6_8

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

Here, we developed a device integrated with a nanochannel and nanostructures to slow DNA translocation velocity. We found that translocation velocity of a single DNA molecule inside a nanochannel was decreased by pre-elongating it using some nanostructures, such as a shallow channel or nanopillars. This decrease of the translocation velocity was associated with the DNA mobility change, which is an intrinsic parameter of DNA molecules and unaffected by an electric field.

DOI： 10.2116/analsci.33.735

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society for Organ Preservation and Biology  

Quantum dots (QDs) have excellent fluorescence properties in comparison to traditional fluorescence probes. Thus, the optical application of QDs is in rapid expansion to each field of analytical chemistry. In this paper, we described about the application of QDs to regenerative medicine, especially stem cell transplantation therapy. Specifically, labeling technologies of stem cells by QDs composed of semiconductor materials in combination with poly-cationic liposome (Lipofectamine^&reg;) or cell penetrating peptide (octa-arginine) were reviewed. Moreover, <i>in vivo</i> imaging of transplanted stem cells in mice by QDs emitting fluorescence in near-infrared region, which could be detected by fluorescence <i>in vivo</i> imaging machines such as IVIS imaging system, was reported.

DOI： 10.11378/organbio.24.201

CiNii Research

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Research

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

© 1973-2012 IEEE. In the field of microfluidics, it is possible to facilitate liquid transport through microsized holes with large slip lengths by lowering the friction at the interface between the flow and the inner surface of the holes. In this paper, we discuss the use of nonequilibrium atmospheric-pressure plasma to modify the surface wettability of microsized holes in glass substrates that are similar to those used as flow channels in glass microfiltration devices. In our experiments, liquid transport flows were driven by internal Laplace pressure differences based on the surface tensions of droplets placed on the front and back sides of the tested substrates.

DOI： 10.1109/TPS.2016.2571721

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

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CiNii Books

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Comprehensive imaging of a biological individual can be achieved by utilizing the variation in spatial resolution, the scale of cathodoluminescence (CL), and near-infrared (NIR), as favored by imaging probe Gd₂O₃ co-doped lanthanide nanophosphors (NPPs). A series of Gd₂O₃:Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) NPPs with multispectral emission are prepared by the sol-gel method. The NPPs show a wide range of emissions spanning from the visible to the NIR region under 980 nm excitation. The dependence of the upconverting (UC)/downconverting (DC) emission intensity on the dopant ratio is investigated. The optimum ratios of dopants obtained for emissions in the NIR regions at 810 nm, 1200 nm, and 1530 nm are applied to produce nanoparticles by the homogeneous precipitation (HP) method. The nanoparticles produced from the HP method are used to investigate the dual NIR and CL imaging modalities. The results indicate the possibility of using Gd₂O₃ co-doped Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) in correlation with NIR and CL imaging. The use of Gd₂O₃ promises an extension of the object dimension to the whole-body level by employing magnetic resonance imaging (MRI).

DOI： 10.3390/nano6090163

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

© 2016 by the authors; licensee MDPI, Basel, Switzerland. We investigated an anomalous DNA separation where two DNA fragments from the human Y-chromosome sY638 (64 bp) and sY592 (65 bp), with only one base pair difference, were separated. This result is abnormal since in a previous study, we found that 5 bp was the minimum difference between two DNA fragments that the microchip electrophoresis system can separate. The formation of a mini-loop in the structure of the DNA fragment of sY638 (64 bp) was strongly expected to be the reason. To investigate this, we synthesized three modified DNA fragments for sY638 (64 bp), and the modifications were in two expected locations for possible mini-loop formation. Later, the separation between sY592 (65 bp) and the three modified fragments of sY638 (64 bp) was not possible. Thus, we conclude that the formation of a mini-loop in the structure of the DNA is the reason behind this anomalous separation.

DOI： 10.3390/scipharm84030507

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Quantitative DNA amplification using fluorescence labeling has played an important role in the recent, rapid progress of basic medical and molecular biological research. Here we report a label-free detection of real-time DNA amplification using a nanofluidic diffraction grating. Our detection system observed intensity changes during DNA amplification of diffracted light derived from the passage of a laser beam through nanochannels embedded in a microchannel. Numerical simulations revealed that the diffracted light intensity change in the nanofluidic diffraction grating was attributed to the change of refractive index. We showed the first case reported to date for label-free detection of real-time DNA amplification, such as specific DNA sequences from tubercle bacilli (TB) and human papillomavirus (HPV). Since our developed system allows quantification of the initial concentration of amplified DNA molecules ranging from 1 fM to 1 pM, we expect that it will offer a new strategy for developing fundamental techniques of medical applications.

DOI： 10.1038/srep31642

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Micromachines  

Dry eye is a problem in tearing quality and/or quantity and it afflicts millions of persons worldwide. An autologous serum eye-drop is a good candidate for dry eye treatment; however, the eye-drop preparation procedures take a long time and are relatively troublesome. Here we use spiral microchannels to demonstrate a strategy for the preparation of autologous serum eye-drops, which provide benefits for all dry eye patients; 100% and 90% removal efficiencies are achieved for 10 μm microbeads and whole human blood cells, respectively. Since our strategy allows researchers to integrate other functional microchannels into one device, such a microfluidic device will be able to offer a new one-step preparation system for autologous serum eye-drops.

DOI： 10.3390/mi7070113

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/mi7070113

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Accurate, sensitive, rapid, and easy operative diagnosis is necessary to prevent the spread of malaria. A cell microarray chip system including a push column for the recovery of erythrocytes and a fluorescence detector was employed for malaria diagnosis in Uganda. The chip with 20,944 microchambers (105 mu m width and 50 mu m depth) was made of polystyrene. For the analysis, 6 mu l of whole blood was employed, and leukocytes were practically removed by filtration through SiO2-nano-fibers in a column. Regular formation of an erythrocyte monolayer in each microchamber was observed following dispersion of an erythrocyte suspension in a nuclear staining dye, SYTO 21, onto the chip surface and washing. About 500,000 erythrocytes were analyzed in a total of 4675 microchambers, and malaria parasite-infected erythrocytes could be detected in 5 min by using the fluorescence detector. The percentage of infected erythrocytes in each of 41 patients was determined. Accurate and quantitative detection of the parasites could be performed. A good correlation between examinations via optical microscopy and by our chip system was demonstrated over the parasitemia range of 0.0039-2.3438% by linear regression analysis (R-2 = 0.9945). Thus, we showed the potential of this chip system for the diagnosis of malaria.

DOI： 10.1038/srep30136

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Dry eye is a problem in tearing quality and/or quantity and it afflicts millions of persons worldwide. An autologous serum eye-drop is a good candidate for dry eye treatment; however, the eye-drop preparation procedures take a long time and are relatively troublesome. Here we use spiral microchannels to demonstrate a strategy for the preparation of autologous serum eye-drops, which provide benefits for all dry eye patients; 100% and 90% removal efficiencies are achieved for 10 mu m microbeads and whole human blood cells, respectively. Since our strategy allows researchers to integrate other functional microchannels into one device, such a microfluidic device will be able to offer a new one-step preparation system for autologous serum eye-drops.

DOI： 10.3390/mi7070113

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Dry eye is a problem in tearing quality and/or quantity and it afflicts millions of persons worldwide. An autologous serum eye-drop is a good candidate for dry eye treatment; however, the eye-drop preparation procedures take a long time and are relatively troublesome. Here we use spiral microchannels to demonstrate a strategy for the preparation of autologous serum eye-drops, which provide benefits for all dry eye patients; 100% and 90% removal efficiencies are achieved for 10 mu m microbeads and whole human blood cells, respectively. Since our strategy allows researchers to integrate other functional microchannels into one device, such a microfluidic device will be able to offer a new one-step preparation system for autologous serum eye-drops.

DOI： 10.3390/mi7070113

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/mi7050082

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

This paper presents a new correlative bioimaging technique using Y2O3:Tm, Yb and Y2O3:Er, Yb nanophosphors (NPs) as imaging probes that emit luminescence excited by both near-infrared (NIR) light and an electron beam. Under 980 nm NIR light irradiation, the Y2O3:Tm, Yb and Y2O3:Er, Yb NPs emitted NIR luminescence (NIRL) around 810 nm and 1530 nm, respectively, and cathodoluminescence at 455 nm and 660 nm under excitation of accelerated electrons, respectively. Multimodalities of the NPs were confirmed in correlative NIRL/CL imaging and their locations were visualized at the same observation area in both NIRL and CL images. Using CL microscopy, the NPs were visualized at the single-particle level and with multicolour. Multiscale NIRL/CL bioimaging was demonstrated through in vivo and in vitro NIRL deep-tissue observations, cellular NIRL imaging, and high-spatial resolution CL imaging of the NPs inside cells. The location of a cell sheet transplanted onto the back muscle fascia of a hairy rat was visualized through NIRL imaging of the Y2O3:Er, Yb NPs. Accurate positions of cells through the thickness (1.5 mm) of a tissue phantom were detected by NIRL from the Y2O3:Tm, Yb NPs. Further, locations of the two types of NPs inside cells were observed using CL microscopy.

DOI： 10.1038/srep25950

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Because nanoparticles with diameters less than 50 nm penetrate stromal-rich tumor tissues more efficiently, the synthesis of small-sized nanoparticles encapsulating short interfering RNA (siRNA) is important in terms of realizing novel siRNA medicine for the treatment of various cancers. Lipid nanoparticles (LNPs) are the leading systems for the delivery of siRNA in vivo. Limit size LNPs were successfully synthesized using a microfluidic mixing technique. However, the physicochemical properties and potential for in vivo siRNA delivery of the limit-size LNPs have not been examined in detail. In the present study, we prepared LNPs with different diameters from 32 to 67 nm using a microfluidic mixing devise and examined the physicochemical properties of the particles and the potential for their use in delivering siRNA in vitro and in vivo to liver. Reducing the size of the LNPs causes poor-packing and an increased surface area, which result in their instability in serum. Moreover, it was revealed that the ability of endosomal escape (cytosolic siRNA release) of the smaller LNPs is subject to inhibition by serum compared to that of larger counterparts. Taken together, an increase in packing and avoiding the adsorption of serum components are key strategies for the development of next-generation highly potent and small-sized LNPs. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jconrel.2016.03.019

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© The Royal Society of Chemistry 2016. This review highlights the most promising applications of nanowires for bioanalytical chemistry and medical diagnostics. The materials discussed here are metal oxide and Si semiconductors, which are integrated with various microfluidic systems. Nanowire structures offer desirable advantages such as a very small diameter size with a high aspect ratio and a high surface-to-volume ratio without grain boundaries; consequently, nanowires are promising tools to study biological systems. This review starts with the integration of nanowire structures into microfluidic systems, followed by the discussion of the advantages of nanowire structures in the separation, manipulation and purification of biomolecules (DNA, RNA and proteins). Next, some representative nanowire devices are introduced for biosensors from molecular to cellular levels based on electrical and optical approaches. Finally, we conclude the review by highlighting some bio-applications for nanowires and presenting the next challenges that must be overcome to improve the capabilities of nanowire structures for biological and medical systems.

DOI： 10.1039/c5lc01306b

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/C6NR01437B

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 17519-17530

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3727/215517916X693159

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3727/215517916X693087

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

World Health Organization grade II and III gliomas most frequently occur in the central nervous system (CNS) in adults. Gliomas are not circumscribed; tumor edges are irregular and consist of tumor cells, normal brain tissue, and hyperplastic reactive glial cells. Therefore, the tumors are not fully resectable, resulting in recurrence, malignant progression, and eventual death. Approximately 69-80% of grade II and III gliomas harbor mutations in the isocitrate dehydrogenase 1 gene (IDH1), of which 83-90% are found to be the IDH1-R132H mutation. Detection of the IDH1-R132H mutation should help in the differential diagnosis of grade II and III gliomas from other types of CNS tumors and help determine the boundary between the tumor and normal brain tissue. In this study, we established a highly sensitive antibody-based device, referred to as the immuno-wall, to detect the IDH1-R132H mutation in gliomas. The immuno-wall causes an immunoreaction in microchannels fabricated using a photo-polymerizing polymer. This microdevice enables the analysis of the IDH1 status with a small sample within 15 min with substantially high sensitivity. Our results suggested that 10% content of the IDH1-R132H mutation in a sample of 0.33 mu l volume, with 500 ng protein, or from 500 cells is theoretically sufficient for the analysis. The immuno-wall device will enable the rapid and highly sensitive detection of the IDH1-R132H mutation in routine clinical practice.

DOI： 10.1080/14686996.2016.1227222

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Rod-shaped AgInTe2 nanocrystals (NCs) exhibiting intense nearband edge photoluminescence in the near-infrared (NIR) wavelength region, were successfully prepared by the thermal reaction of metal acetates and Te precursors in 1-dodecanethiol. Increasing the reaction temperature resulted in the formation of larger AgInTe2 NCs with crystal structures varying from hexagonal to tetragonal at reaction temperatures of 280 degrees C or higher. The energy gap was increased from 1.13 to 1.20 eV with a decrease in rod width from 8.3 to 5.6 nm, accompanied by a blue shift in the photoluminescence (PL) peak wavelength from 1097 to 1033 nm. The optimal PL quantum yield was approximately 18% for AgInTe2 NCs with rod widths of 5.6 nm. The applicability of AgInTe2 NCs as a NIR-emitting material for in vivo biological imaging was examined by injecting AgInTe2 NC-incorporated liposomes into the back of a C57BL/6 mouse, followed by in vivo photoluminescence imaging in the NIR region.

DOI： 10.1039/c5nr07532g

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

A novel capillary electrophoretic method was developed for the assay of two quaternary anti-Parkinson mixtures, entacapone, levodopa, carbidopa, and benserazide (mixture I), and selegiline, levodopa, carbidopa, and benserazide (mixture II), by using alpha-methyldopa as an internal standard. Furthermore, the method was extended for the determination of another anti-Parkinson drug, lisuride, as well as a psychoactive antihypertensive drug, alpha-methyldopa, without any modification of the general method. Separation and analyses of all compounds were simply achieved in an untreated fused-silica capillary tube (42.0 cm effective length and 50 mu m internal diameter) within 7 minutes under an applied voltage of 20 kV. Optimum separation and analyses were obtained using 25 mM borate buffer (pH 9.5) containing 5 mM beta-cyclodextrin as the background electrolyte. The apparatus was equipped with a diode array detector (DAD) to identify lisuride at 240 nm and all other drugs at 200 nm. The addition of 5 mM b-cyclodextrin to the borate buffer has a significant effect on the separation of entacapone and benserazide in mixture I, and on the separation of selegiline and benserazide in mixture II, which cannot be achieved without it. The proposed method was successfully applied to analyse the studied drugs in their multi-component and single-component pharmaceutical dosage forms. The analytical results proved the linearity (r(2) >= 0.9997), accuracy, precision (% RSD < 2), and selectivity of the proposed capillary electrophoretic method.

DOI： 10.1039/c5ra26473a

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1039/c6nr01437b

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

DNA methylation is a stable epigenetic modification, which is well known to be involved in gene expression regulation. In general, however, analyzing DNA methylation requires rather time consuming processes (24-96 h) via DNA replication and protein modification. Here we demonstrate a methodology to analyze DNA methylation at a single DNA molecule level without any protein modifications by measuring the contracted length and relaxation time of DNA within a nanochannel. Our methodology is based on the fact that methylation makes DNA molecules stiffer, resulting in a longer contracted length and a longer relaxation time (a slower contraction rate). The present methodology offers a promising way to identify DNA methylation without any protein modification at a single DNA molecule level within 2 h.
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DOI： 10.1080/14686996.2016.1223516

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CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM  

© 2016, Japan Society of Drug Delivery System. All rights reserved. In vivo imaging diagnostic modalities play important roles in modern medicine. In this paper, we introduced in vivo fluorescence imaging technology of transplanted stem cells using quantum dots. Then, we showed the roles of in vivo fluorescence imaging technology of transplanted stem cells using quantum dots for clinical studies and drug developments of regenerative medicine in various tissues, organs and cancer immunity regions. The drug development in generative medicine is strongly expected by the interdisciplinary approach between in vivo fluorescence imaging technologies based on frontier nanotechnologies and regenerative medicine technologies in the future.

DOI： 10.2745/dds.31.135

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CiNii Books

CiNii Research

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (international conference proceedings)  

We developed a size-exclusive micro sand timer in which a single cancer cell was trapped at the narrow neck through a trickle of blood from the upper bulb to the lower one. The cells in the bulbs could be directly subjected to enumeration and staining assays for identification of cancer cells in blood. A cell population with tumor markers was successfully detected as distinguished from other blood cells.

Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016  

We developed a size-exclusive micro sand timer in which a single cancer cell was trapped at the narrow neck through a trickle of blood from the upper bulb to the lower one. The cells in the bulbs could be directly subjected to enumeration and staining assays for identification of cancer cells in blood. A cell population with tumor markers was successfully detected as distinguished from other blood cells.

Scopus

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016  

We report a highly-sensitive microchip electrophoretic method for the simultaneous analysis of gabapentin (GPN) and pregabalin (PGN). Analyses and separation of both compounds were achieved in a PMMA microchip after labelling with 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). The separation of the labelled compounds was improved by addition of β-cyclodextrin (β-CD). Moreover, methylcellulose polymer was added to prevent analytes' adsorption on the microchannel walls. The sensitivity of the method was improved by stacking to quantify as low as 0.06 nM of each drug with detection limits of 12 pM.

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.addr.2015.11.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

A field of recent diagnostics and therapeutics has been advanced with quantum dots (QDs). QDs have developed into new formats of biomolecular sensing to push the limits of detection in biology and medicine. QDs can be also utilized as bio-probes or labels for biological imaging of living cells and tissues. More recently, QDs has been demonstrated to construct a multifunctional nanoplatform, where the QDs serve not only as an imaging agent, but also a nanoscaffold for diagnostic and therapeutic modalities. This review highlights the promising applications of multi-functionalized QDs as advanced nanosensors for diagnosing cancer and as innovative fluorescence probes for in vitro or in vivo stem cell imaging in regenerative medicine. (C) 2015 Elsevier B.V. All rights resrved.

DOI： 10.1016/j.addr.2015.08.004

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2116/analsci31.1197

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC ANALYTICAL CHEMISTRY  

Development of polymeric microfluidic devices has played an important role in the recent, rapid progress of biomedical research. Here we report a fabrication method for micropillars on poly(methyl methacrylate) (PMMA) substrates for separation of microscale objects. The fabricated micropillars enable continuous separation of microparticles only by introducing fluids. The present method offers a new strategy to fabricate polymeric prototype devices for R&D work.

DOI： 10.2116/analsci.31.1197

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Web of Science

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本バイオマテリアル学会  

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)