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Publications (152)
Maintaining healthy life in old age (healthy aging) is an important social challenge. An effective approach to realizing healthy aging involves providing personalized healthcare through disease prevention, early diagnostics, and optimal treatments. Nanobiodevices and quantum life sciences have tremendous potential to revolutionize current technique...
DNA methylation is a crucial epigenetic modification used as a biomarker for early cancer progression. However, existing methods for DNA methylation analysis are complex, time-consuming, and prone to DNA degradation. This work demonstrates selective capture of unmethylated DNAs using ZnO nanowires without chemical or biological modifications, there...
Extracellular vesicles (EVs) have been considered as biomarkers for diagnosis and prognosis in therapeutic treatments. Although applications of EVs in health care are being started and more are expected, EV studies have not yet provided a deep understanding of EV biogenesis and functions. So, comprehensive study of EVs continues. To gain a better u...
Extracellular vesicles (EVs) from cancer cells promote abnormal growth in normal cells, potentially leading to cancer proliferation. We developed a nanowire-based EV-elimination device that efficiently eliminated EVs without toxicity. This method restored normal growth in mammary gland cells cultured with breast adenocarcinoma-derived EVs containin...
Multiple microRNAs encapsulated in extracellular vesicles (EVs) including exosomes, unique subtypes of EVs, differ in healthy and cancer groups of people, and they represent a warning sign for various cancer scenarios. Since all EVs in blood cannot be transferred from donor to recipient cells during a single blood circulation, kidney filtration cou...
Liquid biopsy has emerged as a revolutionary diagnostic approach for analyzing cancer-related biomolecules in bodily fluids, providing a non-invasive and dynamic method for cancer detection and monitoring. However, its practical application in the medical field is often hindered by the complexities of body fluids that pose challenges in the collect...
Congenital diaphragmatic hernia (CDH) is a life‐threatening condition with high morbidity and mortality rates. The survival rate of neonates with severe CDH is reportedly only 10%–15%. However, prenatal prediction of severe cases is difficult, and the discovery of new predictive markers is an urgent issue. In this study, we focused on microRNAs (mi...
Extracellular vesicles (EVs) contain a subset of proteins, lipids, and nucleic acids that maintain the characteristics of the parent cell. Immunotherapy using EVs has become a focus of research due to their unique features and bioinspired applications in cancer treatment. Unlike conventional immunotherapy using tumor fragments, EVs can be easily ob...
Extracellular vesicles (EVs), including exosomes, are recognized as promising functional tools involved in cancer progression. Although evidence of the functions of EV in cancer biology has been accumulating, optimizing EV isolation is still a major challenge. In ovarian cancer, peritoneal dissemination is a crucial prognostic factor due to the lac...
Extracellular vesicles (EVs), including exosomes, are recognized as promising functional targets involved in disease mechanisms. However, the intravital heterogeneity of EVs remains unclear, and the general limitation for analyzing EVs is the need for a certain volume of biofluids. Here, we present cellulose nanofiber (CNF) sheets to resolve these...
Rapid and sensitive detection of Dengue virus remains a critical challenge in global public health. This study presents the development and evaluation of a Zinc Oxide nanorod (ZnO NR)-surface-integrated microfluidic platform for the early detection of Dengue virus. Utilizing a seed-assisted hydrothermal synthesis method, high-purity ZnO NRs were sy...
A low-temperature Al2O3 deposition process provides a simplified method to form a conductive two-dimensional electron gas (2DEG) at the metal oxide/Al2O3 heterointerface. However, the impact of key factors of the interface defects and cation interdiffusion on the interface is still not well understood. Furthermore, there is still a blank space in t...
Cancer cell-derived extracellular vesicles (EVs) have unique protein profiles, making them promising targets as disease biomarkers. High-grade serous ovarian carcinoma (HGSOC) is the deadly subtype of epithelial ovarian cancer, and we aimed to identify HGSOC-specific membrane proteins. Small EVs (sEVs) and medium/large EVs (m/lEVs) from cell lines...
Cell-free DNA (cfDNA) and extracellular vesicles (EVs) are molecular biomarkers in liquid biopsies that can be applied for cancer detection, which are known to carry information on the necessary conditions for oncogenesis and cancer cell-specific activities after oncogenesis, respectively. Analyses for both cfDNA and EVs from the same body fluid ca...
MicroRNAs (miRNAs) within extracellular vesicles (EVs) in body fluids may serve as biomarkers for low-invasive early diseases diagnostics. Although isolation of EVs in body fluids is a crucial step for analyzing miRNAs within the EVs, conventional techniques face challenges due to their low isolation efficiency and requirements of large sample volu...
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 m...
Nanobiodevices, a technology characterized by engineered nanostructures, have attracted extensive interest as a new generation bioanalytical tool that allows accessing the information contained in nucleic acids. Distinct properties of nanobiodevice technologies have shown great promise in improvements in sensitivity, speed, and accuracy for nucleic...
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 analys...
Correction for ‘Breath odor-based individual authentication by an artificial olfactory sensor system and machine learning’ by Chaiyanut Jirayupat et al. , Chem. Commun ., 2022, DOI: https://doi.org/10.1039/D1CC06384G.
The potential feasibility of breath odor sensing-based individual authentication was demonstrated by a 16-channel chemiresistive sensor array and machine learning.
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 t...
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...
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 t...
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...
microRNAs modulate gene expression in various cancer types, and their profiles differ in healthy and cancer groups of people and they represent a warning sign for various cancer scenarios. Identification of tumor-specific microRNAs presents a powerful opportunity to potentially reduce cancer mortality through early detection. In order to achieve ea...
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 met...
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 cer...
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-stag...
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 parenc...
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-confine...
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. Rec...
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. Howev...
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 comp...
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 mi...
Electrical molecular nanosensors require two conflicting surface characteristics, including a catalytic activity for molecular selectivity and a thermal stability for long-term data collection. Here, we show that a simple surface treatment using strong acids creates such two conflicting surface properties of WO3 hydrate nanowires to enhance the ele...
Since DNA analysis is the fundamental process for most applications in biomedical fields, capturing DNAs with high efficiency has been 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 arou...
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...
Fine particulate matter sized 2.5 μm or less, referred to as PM2.5, 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 a...
This paper describes a horizontal miniature developing chamber suitable for ultrathin layer chromatography (UTLC) and TLC-MS. The miniature developing chamber was designed by a CAD system and cut out from a PTFE block with a milling machine. The basic performance of the laboratory-made chambers was evaluated through TLC separations of lipids extrac...
Ammonia is a well-known additive to promote the crystal growth in hydrothermal synthesis of ZnO nanowires. Although the effect of ammonia on the nanowire growth has been intensively investigated, an influence for the seed layer, which governs the initial nanowire growth, is rarely discussed. Here we demonstrate that ammonia strongly affects the see...
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...
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 biom...
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 Zn...
A sparse ZnO nanowire array with aspect ratio of ca. 120 and growth rate of 1 μm/h was synthesized by controlling the density of seeds at the initial stage of nanowire growth. The spatially-separated nanowires were cut off from the growth substrate without breaking, and thus were useful in the construction of a single-nanowire device by photolithog...
The liposome–protamine–DNA complex (LPD) is an effective cationic carrier of various nucleic acid constructs such as plasmid DNA and small interfering RNA (siRNA). Hyaluronic acid coated on LPD (LPDH) reduces cytotoxicity and maintains the silencing effect of LPD-encapsulated siRNA. Herein, we aim to develop LPD- or LPDH-containing spray-freeze-dri...
Here we discuss a chemical capping misunderstanding, which has intrinsically hindered to extend the length of hexagonal(h)-WO3 nanowires in previous studies. Although divalent sulfate ions (SO4²⁻) have been strongly believed as efficient capping ions to direct an anisotropic h-WO3 nanowire growth, we found that the presence of SO4²⁻ is highly detri...
Extracellular vesicles (EVs) play an important role in cell-to-cell communication carrying molecular messages which reflect physiological and pathological conditions of the parent cells. EVs have been identified in all body fluids; and among them, urine stands out as a sample that is easy and inexpensive to obtain and can be collected over time to...
The detection of circulating tumor cells (CTCs) from liquid biopsies using microfluidic devices is attracting a considerable amount of attention as a new, less-invasive cancer diagnostic and prognostic method. One of the drawbacks of the existing antibody-based detection systems is the false negatives for epithelial cell adhesion molecule detection...
We demonstrate the facile, rational synthesis of monodispersedly sized zinc oxide (ZnO) nanowires from randomly sized seeds by hydrothermal growth. Uniformly shaped nanowire tips constructed in ammonia-dominated alkaline conditions serve as a foundation for the subsequent formation of the monodisperse nanowires. By precisely controlling the sharp t...
BACKGROUND
Diffuse gliomas are the most common primary malignant brain tumors, whose overall prognosis is quite dismal. Tumor-cell-secreted extracellular vesicles (EVs) participate in physiological and pathological processes and have potential applications to diagnostics of malignant tumors including diffuse gliomas. Because urine is less invasive...
A crystal growth of hydrothermal ZnO nanowires essentially requires a concentration control within so-called “concentration window”, where the anisotropic crystal growth of ZnO nanowires preferentially occurs. Although understanding what exactly determines the width of “concentration window” is important to tailor the anisotropic crystal growth pro...
The mechanical properties of a cell, which include parameters such as elasticity, inner pressure, and tensile strength, are extremely important because changes in these properties are indicative of disease ranging from diabetes to malignant transformation. Considering the heterogeneity within a population of cancer cells, a robust measurement syste...
Here, we show the effect of water-organic (acetone, tert-butyl alcohol, and isopropanol) cosolvents on nucleation and anisotropic crystal growth of solution-synthesized ZnO nanowires. The addition of organic solution does not alter the face-selective crystal growth nature but significantly promotes the crystal growth of both length and diameter of...
Micro- and nanopillar chips are widely used to separate and enrich biomolecules, such as DNA, RNA, protein, and cells, as an analytical technique and to provide a confined nanospace for polymer science analyses. Herein, we demonstrated a continuous accurate and precise separation technique for extracellular vesicles (EVs)—nanometer-sized vesicles (...
Metal oxide nanowires have demonstrated excellent capability in the electrical detection of various molecules, based on their material robustness in liquid and air environments. Although the surface structure of the nanowires essentially determines their interaction with adsorbed molecules, understanding the correlation between an oxide nanowire su...
Researchers have demonstrated great promise for inorganic nanowire use in analyzing cells or intracellular components. Although a stealth effect of nanowires toward cell surfaces allows preservation of the living intact cells when analyzing cells, as a completely opposite approach, the applicability to analyze intracellular components through disru...
We have demonstrated a PM2.5 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 PM2.5 particles, even if a relatively large micropore is used. This is the fir...
Molecular recognition is one of the key factors in designing biosensors due to which nanowires functionalized with molecular recognition have attracted a lot of attention as promising candidates for nanostructures embedded in biosensors. However, the difficulty in real-world applications with analytical specificity is that molecular recognition on...
Rapid detection of pathogenic bacteria is one of the important social issues for preventing and identifying cause of problems affecting human health. Ionic current sensing through pores has shown the ability to electrically measure bacteria. However, there is an inherent limitation to discriminate chemical characteristics of bacteria for existing i...
Hepatocellular carcinoma (HCC) is a typical hyper-vascular tumor, so the understanding the mechanisms of angiogenesis in HCC is very important for its treatment. However, the influence of the exosomes secreted from HCC cells (HCC-exosomes) on angiogenesis remains poorly understood. We herein examined the effects of the exosomes secreted from HepG2...
In the present study, we quantitatively evaluated dielectric breakdown in silicon-based micro- and nanofluidic devices under practical electrophoretic conditions by changing the thickness of the insulating layer. At higher buffer concentration, a silicon nanofluidic device with a 100 nm or 250 nm silicon dioxide layer tolerated dielectric breakdown...
Ionic current sensing methods are useful tools for detecting sub- to several-micron scale particles such as bacteria. However, conventional commercially available ionic current sensing devices are not suitable for on-site measurement use because of inherent limitations on their robustness. Here, we proposed a portable robust ionic current sensor (R...
Bridge circuit based ionic current sensing in a microfluidic channel has attracted attention as a highly sensitive analytical method for bio-related molecules and particles. However, channel geometry which greatly influences the detected ionic current has not been investigated. Here, we investigate experimentally and theoretically the effect of dif...
Conventional concepts of resistive pulse analysis is to discriminate particles in liquid by the difference in their size through comparing the amount of ionic current blockage. In sharp contrast, we herein report a proof-of-concept demonstration of the shape sensing capability of solid-state pore sensors by leveraging the synergy between nanopore t...
Analyzing microRNAs (miRNAs) within urine extracellular vesicles (EVs) is important for realizing miRNA-based, simple, and noninvasive early disease diagnoses and timely medical checkups. However, the inherent difficulty in collecting dilute concentrations of EVs (<0.01 volume %) from urine has hindered the development of these diagnoses and medica...
Lipid nanoparticles (LNPs) or liposomes are the most widely used drug carriers for nanomedicines. The size of LNPs is one of the essential factors affecting drug delivery efficiency and therapeutic efficiency. Here, we demonstrated the effect of lipid concentration and mixing performance on the LNP size using microfluidic devices with the aim of un...
The LNP size formed in the three types of microfluidic devices at FRR of 7.
The error bars represent the standard deviation calculated form repeating each LNP formation experiment at least three times.
(TIFF)
The mixing rate in the microfluidic devices at FRR of 3.
(TIFF)
Relationship between the PDI values and the lipid concentrations.
The particle size polydispersity index (PDI) was calculated by the measurement of dynamic light scattering. The flow rates were 100 and 500 μL/min and the FRRs were set at 3 to 49. The error bars represent the standard deviation calculated from repeating each LNP formation experiment...
The mixing rate in the microfluidic devices at FRR of 9.
(TIFF)
Measuring ionic currents passing through nano- or micro-pores has shown great promise for the electrical discrimination of various biomolecules, cells, bacteria, and viruses. However, conventional measurements have shown there is an inherent limitation to the detectable particle volume (1% of the pore volume), which critically hinders applications...
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 as...
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 attribute...
Single-molecule detection of the biomolecules in a label-free manner has a tremendous impact for various fields. Recently, we developed a label-free detection method without any pretreatment procedures, which is based on optical diffraction derived from a nanofluidic channel array (in other words, a nanowall array). However, the single-molecule det...
A millisecond micro-RNA separation of a mixture of total RNA and genomic DNA, extracted from cultured HeLa cells, was successfully achieved using a hybrid structure of nanopillars and nanoslits contained inside a microchannel. The nanopillars, 250-nm in diameter and 100-nm in height, were fabricated with a 750-nm space inside the nanoslits, which w...
There has been significant growth in the field of nanofluidics, where nanoscale analytical instruments employ micromachined features and are able to manipulate fluid samples with high precision and efficiency and have many advantages over their conventional (larger) analogues.
The new edition of Nanofluidics has been fully revised and updated with...
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 l...
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 amplificati...
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...
Functional near-IR (NIR) emitting nanoparticles (NPs) adapted for in-vitro two-photon excitation fluorescence cell imaging were obtained starting from octadecyl-terminated silicon nanocrystals (ncSi-OD) of narrow and symmetric photoluminescence (PL) spectra, PL quantum yields higher than 30%, PL lifetimes of 300 sec or longer, and continuously tun...
This review highlights the most promising applications of nanowires for bioanalytical chemistry and medical diagnostics. The materials discussed here are metal oxide semiconductors and Si, which are integrated with various microfluidic systems. Nanowire structures offer desirable advantages such as a very small diameter size with a high aspect rati...
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...
