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        Extremely sensitive and wide-range silver ion detection via assessing the integrated surface potential of a DNA-capped gold nanoparticle

        Lee, Dongtak,Lee, Hyungbeen,Lee, Gyudo,Kim, Insu,Lee, Sang Won,Kim, Woong,Lee, Sang Woo,Lee, Jeong Hoon,Park, Jinsung,Yoon, Dae Sung IOP 2019 Nanotechnology Vol.30 No.8

        <P>With the rapid development of nanotechnology and its associated waste stream, public concern is growing over the potential toxicity exposure to heavy metal ions poses to the human body and the environment. Herein, we report an extremely sensitive Kelvin probe force microscopy (KPFM)-based platform for detecting nanotoxic materials (e.g. Ag<SUP>+</SUP>) accomplished by probing the integrated surface potential differences of a single gold nanoparticle on which an interaction between probe DNA and target DNA occurs. This interaction can amplify the surface potential of the nanoparticle owing to the coordination bond mediated by Ag<SUP>+</SUP> (cytosine–Ag<SUP>+</SUP>–cytosine base pairs). Interestingly, compared with conventional methods, this platform is capable of extremely sensitive Ag<SUP>+</SUP> detection (∼1 fM) in a remarkably wide-range (1 fM to 1 <I>μ</I>M). Furthermore, this platform enables Ag<SUP>+</SUP> detection in a practical sample (general drinking water), and this KPFM-based technique may have the potential to detect other toxic heavy metal ions and single nucleotide polymorphisms by designing specific DNA sequences.</P>

      • Identifying DNA mismatches at single-nucleotide resolution by probing individual surface potentials of DNA-capped nanoparticles

        Lee, Hyungbeen,Lee, Sang Won,Lee, Gyudo,Lee, Wonseok,Nam, Kihwan,Lee, Jeong Hoon,Hwang, Kyo Seon,Yang, Jaemoon,Lee, Hyeyoung,Kim, Sangsig,Lee, Sang Woo,Yoon, Dae Sung The Royal Society of Chemistry 2018 Nanoscale Vol.10 No.2

        <P>Here, we demonstrate a powerful method to discriminate DNA mismatches at single-nucleotide resolution from 0 to 5 mismatches (<I>χ</I>0 to <I>χ</I>5) using Kelvin probe force microscopy (KPFM). Using our previously developed method, we quantified the surface potentials (SPs) of individual DNA-capped nanoparticles (DCNPs, ∼100 nm). On each DCNP, DNA hybridization occurs between ∼2200 immobilized probe DNA (<I>p</I>DNA) and target DNA with mismatches (<I>t</I>DNA, ∼80 nM). Thus, each DCNP used in the bioassay (each <I>p</I>DNA-<I>t</I>DNA interaction) corresponds to a single ensemble in which a large number of <I>p</I>DNA-<I>t</I>DNA interactions take place. Moreover, one KPFM image can scan at least dozens of ensembles, which allows statistical analysis (<I>i.e.</I>, an ensemble average) of many bioassay cases (ensembles) under the same conditions. We found that as the <I>χ</I>n increased from <I>χ</I>0 to <I>χ</I>5 in the tDNA, the average SP of dozens of ensembles (DCNPs) was attenuated owing to fewer hybridization events between the <I>p</I>DNA and the <I>t</I>DNA. Remarkably, the SP attenuation <I>vs.</I> the <I>χ</I>n showed an inverse-linear correlation, albeit the equilibrium constant for DNA hybridization exponentially decreased asymptotically as the <I>χ</I>n increased. In addition, we observed a cascade reaction at a 100-fold lower concentration of <I>t</I>DNA (∼0.8 nM); the average SP of DCNPs exhibited no significant decrease but rather split into two separate states (no-hybridization <I>vs.</I> full-hybridization). Compared to complementary <I>t</I>DNA (<I>i.e.</I>, <I>χ</I>0), the ratio of no-hybridization/full-hybridization within a given set of DCNPs became ∼1.6 times higher in the presence of tDNA with single mismatches (<I>i.e.</I>, <I>χ</I>1). The results imply that our method opens new avenues not only in the research on the DNA hybridization mechanism in the presence of DNA mismatches but also in the development of a robust technology for DNA mismatch detection.</P>

      • SCISCIESCOPUS

        Microwave-induced formation of oligomeric amyloid aggregates

        Lee, Wonseok,Choi, Yeseong,Lee, Sang Won,Kim, Insu,Lee, Dongtak,Hong, Yoochan,Lee, Gyudo,Yoon, Dae Sung IOP 2018 Nanotechnology Vol.29 No.34

        <P>Amyloid aggregates have emerged as a significant hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Although it has been recently reported that microwave heating induces amyloid aggregation compared with conventional heating methods, the mechanism of amyloid aggregate induction has remained unclear. In this study, we investigated the formation of oligomeric amyloid aggregates (OAAs) by microwave irradiation at microscale volumes of solution. Microwave irradiation of protein monomer solution triggered rapid formation of OAAs within 7 min. We characterized the formation of OAAs using atomic force microscopy, thioflavin T fluorescent assay and circular dichroism. In the microwave system, we also investigated the inhibitory effect on the formation of amyloid aggregates by L-ascorbic acid as well as enhanced amyloid aggregation by silver nanomaterials such as nanoparticles and nanowires. We believe that microwave technology has the potential to facilitate the study of amyloid aggregation in the presence of chemical agents or nanomaterials.</P>

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        A simple and disposable carbon adhesive tape-based NO<sub>2</sub> gas sensor

        Lee, Sang Won,Lee, Wonseok,Lee, Dongtak,Choi, Yeseong,Kim, Woong,Park, Jinsung,Lee, Jeong Hoon,Lee, Gyudo,Yoon, Dae Sung Elsevier 2018 Sensors and actuators. B Chemical Vol.266 No.-

        <P><B>Abstract</B></P> <P>Nitrogen dioxide (NO<SUB>2</SUB>) is one of the toxic gas that causes debilitating disease in the respiratory system. Due to imprudent industrial development, the need for a facile and sensitive gas detection has been grown. Here, we develop a simple and disposable NO<SUB>2</SUB> gas sensor employing carbon adhesive tape (CAT) as the gas detection element. The CAT developed in this study contained a large amount of carbon black material to adsorb NO<SUB>2</SUB> gas molecules. Experiments revealed that the gas molecules were bound rapidly to the CAT sensor (<3 min). The chemical and physical characteristics of the CAT were investigated by thermal gravimetric analysis, X-ray photoelectron spectroscopy, and scanning electron microscopy. With increases of bound NO<SUB>2</SUB> gas molecules, electrical conductance was augmented. Analytical sensitivity of the CAT-based gas sensor was estimated to be 5 ppm, lower than the concentration generally considered as a minimum concentration to cause harm to people. In addition, we tested such CAT sensor for detecting NO<SUB>x</SUB> from car exhaust, suggesting the possibility of its practical application. Taken together, our results indicate that CAT-based gas sensor developed in this study is applicable as a robust, facile, and disposable NO<SUB>2</SUB> gas sensing platform.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CAT-based gas sensor is applicable as a robust, facile, and disposable NO<SUB>2</SUB> gas sensing platform. </LI> <LI> Electrical conductance of CAT chip is increased depending on the exposure time (0–10 min) and concentration (0–100 ppm) of NO<SUB>2</SUB> gas. </LI> <LI> Detection time of NO<SUB>2</SUB> gas is less than 3 min with enough sensitivity (∼5 ppm) which is lower than the concentration generally considered as a minimum concentration (10 ppm) to cause harm to human. </LI> <LI> CAT chip can detect NO<SUB>2</SUB> gas from the car exhausts such as gasoline and diesel regardless of humidity (H<SUB>2</SUB>O), carbon dioxide (CO<SUB>2</SUB>), nitrogen (N<SUB>2</SUB>) and dust. </LI> </UL> </P>

      • Nanomechanical characterization of chemical interaction between gold nanoparticles and chemical functional groups

        Lee, Gyudo,Lee, Hyungbeen,Nam, Kihwan,Han, Jae-Hee,Yang, Jaemoon,Lee, Sang Woo,Yoon, Dae Sung,Eom, Kilho,Kwon, Taeyun Springer 2012 Nanoscale research letters Vol.7 No.1

        <P>We report on how to quantify the binding affinity between a nanoparticle and chemical functional group using various experimental methods such as cantilever assay, PeakForce quantitative nanomechanical property mapping, and lateral force microscopy. For the immobilization of Au nanoparticles (AuNPs) onto a microscale silicon substrate, we have considered two different chemical functional molecules of amine and catecholamine (here, dopamine was used). It is found that catecholamine-modified surface is more effective for the functionalization of AuNPs onto the surface than the amine-modified surface, which has been shown from our various experiments. The dimensionless parameter (i.e., ratio of binding affinity) introduced in this work from such experiments is useful in quantitatively depicting such binding affinity, indicating that the binding affinity and stability between AuNPs and catecholamine is approximately 1.5 times stronger than that between amine and AuNPs. Our study sheds light on the experiment-based quantitative characterization of the binding affinity between nanomaterial and chemical groups, which will eventually provide an insight into how to effectively design the functional material using chemical groups.</P>

      • Real-Time Analysis of Cellular Response to Small-Molecule Drugs within a Microfluidic Dielectrophoresis Device

        Park, In Soo,Lee, Jaewoo,Lee, Gyudo,Nam, Kihwan,Lee, Taewoo,Chang, Woo-Jin,Kim, Hansung,Lee, Sei-Young,Seo, Jongbum,Yoon, Dae Sung,Lee, Sang Woo American Chemical Society 2015 ANALYTICAL CHEMISTRY - Vol.87 No.12

        <P>Quantitative detection of the biological properties of living cells is essential for a wide range of purposes, from the understanding of cellular characteristics to the development of novel drugs in nanomedicine. Here, we demonstrate that analysis of cell biological properties within a microfluidic dielectrophoresis device enables quantitative detection of cellular biological properties and simultaneously allows large-scale measurement in a noise-robust and probeless manner. Applying this technique, the static and dynamic biological responses of live B16F10 melanoma cells to the small-molecule drugs such as <I>N</I>-ethylmaleimide (NEM) and [(dihydronindenyl)oxy]alkanoic acid (DIOA) were quantitatively and statistically examined by investigating changes in movement of the cells. Measurement was achieved using subtle variations in dielectrophoresis (DEP) properties of the cells, which were attributed to activation or deactivation of K<SUP>+</SUP>/Cl<SUP>–</SUP> cotransporter channels on the cell membrane by the small-molecule drugs, in a microfluidic device. On the basis of quantitative analysis data, we also provide the first report of the shift of the complex permittivity of a cell induced by the small-molecule drugs. In addition, we demonstrate interesting quantifiable parameters including the drug effectiveness coefficient, antagonistic interaction coefficient, kinetic rate, and full width at half-maximum, which corresponded to changes in biological properties of B16F10 cells over time when NEM and DIOA were introduced alone or in combination. Those demonstrated parameters represent very useful tools for evaluating the effect of small-molecule drugs on the biological properties of cells.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancham/2015/ancham.2015.87.issue-12/ac5041549/production/images/medium/ac-2014-041549_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ac5041549'>ACS Electronic Supporting Info</A></P>

      • Real‐Time Quantitative Monitoring of Specific Peptide Cleavage by a Proteinase for Cancer Diagnosis

        Lee, Gyudo,Eom, Kilho,Park, Joseph,Yang, Jaemoon,Haam, Seungjoo,Huh, Yong‐,Min,Ryu, Joo Kyung,Kim, Nam Hee,Yook, Jong In,Lee, Sang Woo,Yoon, Dae Sung,Kwon, Taeyun WILEY‐VCH Verlag 2012 Angewandte Chemie Vol.124 No.24

        <P><B>Gute Schwingungen</B>: Ein resonanter Massesensor, auf dessen Oberfläche Peptide immobilisiert sind, wird in einem Bioassay verwendet, mit dem die proteolytische Aktivität der Membran‐Typ‐1‐Matrix‐Metalloproteinase (MT1‐MMP) bestimmt werden kann. Dabei werden Änderungen in der Frequenz des Massesensors gemessen, die nach der spezifischen proteolytischen Spaltung der immobilisierten Zielpeptide durch MT1‐MMP auftreten (siehe Bild).</P>

      • Electrochemical detection of high-sensitivity CRP inside a microfluidic device by numerical and experimental studies.

        Lee, Gyudo,Park, Insu,Kwon, Kiwoon,Kwon, Taeyun,Seo, Jongbum,Chang, Woo-Jin,Nam, Hakhyun,Cha, Geun Sig,Choi, Moon Hee,Yoon, Dae Sung,Lee, Sang Woo Kluwer Academic Publishers 2012 Biomedical microdevices Vol.14 No.2

        <P>The concentration of C-reactive protein (CRP), a classic acute phase plasma protein, increases rapidly in response to tissue infection or inflammation, especially in cases of cardiovascular disease and stroke. Thus, highly sensitive monitoring of the CRP concentration plays a pivotal role in detecting these diseases. Many researchers have studied methods for the detection of CRP concentrations such as optical, mechanical, and electrochemical techniques inside microfluidic devices. While significant progress has been made towards improving the resolution and sensitivity of detection, only a few studies have systematically analyzed the CRP concentration using both numerical and experimental approaches. Specifically, systematic analyses of the electrochemical detection of high-sensitivity CRP (hsCRP) using an enzyme-linked immunosorbant assay (ELISA) inside a microfluidic device have never been conducted. In this paper, we systematically analyzed the electrochemical detection of CRP modified through the attachment of an alkaline phosphatase (ALP-labeled CRP) using ELISA inside a chip. For this analysis, we developed a model based on antigen-antibody binding kinetics theory for the numerical quantification of the CRP concentration. We also experimentally measured the current value corresponding to the ALP-labeled CRP concentration inside the microfluidic chip. The measured value closely matched the calculated value obtained by numerical simulation using the developed model. Through this comparison, we validated the numerical simulation methods, and the calculated and measured values. Lastly, we examined the effects of various microfluidic parameters on electrochemical detection of the ALP-labeled CRP concentration using numerical simulations. The results of these simulations provide insight into the microfluidic electrochemical reactions used for protein detection. Furthermore, the results described in this study should be useful for the design and optimization of electrochemical immunoassay chips for the detection of target proteins.</P>

      • SCISCIESCOPUS

        Experimental and numerical study of electrochemical nanomachining using an AFM cantilever tip

        Lee, Gyudo,Jung, Huihun,Son, Jongsang,Nam, Kihwan,Kwon, Taeyun,Lim, Geunbae,Kim, Young Ho,Seo, Jongbum,Lee, Sang Woo,Yoon, Dae Sung IOP Pub 2010 Nanotechnology Vol.21 No.18

        <P>We fabricated nanopatterns on Cu thin films via an electrochemical route using an atomic force microscope (AFM). Experimental results were compared with an equivalent electrochemical circuit model representing an electrochemical nanomachining (ECN) technique. In order to precisely construct the nanopatterns, an ultra-short pulse was applied onto the Cu film through the AFM cantilever tip. The line width of the nanopatterns (the lateral dimension) increased with increased pulse amplitude, on-time, and frequency. The tip velocity effect on the nanopattern line width was also investigated. The study described here provides important insight for fabricating nanopatterns precisely using electrochemical methods with an AFM cantilever tip. </P>

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