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      • Amphiphilic triblock copolymer and a microfluidic device for porous microfiber fabrication

        Marimuthu, Mohana,Kim, Sanghyo,An, Jeongho Royal Society of Chemistry 2010 SOFT MATTER Vol.6 No.10

        <P>This paper shows successful fabrication of different diameter porous microfibers using a novel, simple and cost effective polydimethylsiloxane (PDMS)-based microfluidic device in which an amphiphilic ABA triblock copolymer, poly(<I>p</I>-dioxanone-<I>co</I>-caprolactone)-<I>block</I>-poly(ethylene oxide)-<I>block</I>-poly(<I>p</I>-dioxanone-<I>co</I>-caprolactone) (PPDO-<I>co</I>-PCL-<I>b</I>-PEG-<I>b</I>- PPDO-<I>co</I>-PCL) in dichloromethane (CH<SUB>2</SUB>Cl<SUB>2</SUB>), and de-ionized water (DI H<SUB>2</SUB>O) were taken in two inlets to extrude porous fibers through the outlet utilizing a dual mechanism of immersion precipitation and solvent evaporation. The flow rates of the two inlet solutions (core and sheath) were controlled such that 5–50 μl min<SUP>−1</SUP> and 100 ml h<SUP>−1</SUP> were used, respectively, to produce 2–200 μm diameter porous microfibers. Controlled fibronectin (an adhesive protein) release from the scaffold was observed until 8 weeks in an <I>in vitro</I> protein release study, which could be due to the slower scaffold PCL block degradation rate until 8 weeks of the <I>in vitro</I> degradation analysis. Cytocompatibility of our porous scaffold was demonstrated for its applicability as a cell culture scaffold or implant material by means of analysis of surface hydrophilicity (water and cell suspension contact angles) and mitochondrial activity (WST-1 proliferation test) using L929 mouse fibroblasts cell line. In summary, the experimental results suggest that combined use of the microfluidic device and amphiphilic triblock copolymer produces varied diameter porous fiber scaffolds which can be potentially used as a controlled protein/drug release carrier for tissue regeneration and/or drug delivery applications.</P> <P>Graphic Abstract</P><P>Porous microfibers with different diameters were successfully fabricated using a novel, simple and cost effective polydimethylsiloxane (PDMS)-based microfluidic device in which an amphiphilic ABA triblock copolymer was used. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b924704a'> </P>

      • KCI등재

        Continuous Oxygen Supply in Pump-less Micro-Bioreactor Based on Microfluidics

        Mohana Marimuthu,김상효 한국바이오칩학회 2015 BioChip Journal Vol.9 No.1

        This research aims a continuous and uniformoxygen tensions and oxygen gradients supply inmicrofluidic cell culture chip based micro-bioreactorwithout any external pumps by modifying the existingsiphon based perfusion strategy using conventionaltools to control constant hydrostatic pressure for constantfluid flow rate. In this study, the microfluidicbased micro-bioreactor is fabricated using a polydimethylsiloxane(PDMS) replication process. The micro-bioreactor chip is composed of simple oxygenperfusion setup connecting to capillary-like branchedmicrochannels and a cell culture and support loadingarea. The function of the new pump-less fluid perfusionin microfluidic cell culture chip and maintainsconstant oxygen supply in the cell culture area hasbeen experimentally evaluated. And the results demonstratethat this proposed microfluidic flow systemin a micro-bioreactor is proved to provide a linear distributionof oxygen throughout the cell culture areawithout any external and internal interference. Also,oxygen diffusion into the culture area through a microscalechannel has been successfully established bythe constant hydraulic pressure controlled by siphoningeffect. Such flow system was used in a PDMSbased microfluidic micro-bioreactor design to providethe high-throughput oxygen diffusion and perfusion,and the uniform oxygen/nutrient distribution continuouslysupplied for dermal fibroblast cell culture. Thiscould be a potential and effective model to be incorporatedinto tissue regeneration studies, drug screeningmodel, and in cancer tissue model studies for understandingangiogenesis, where oxygen tension andperfusion cultures play important roles.

      • Real-time electrical measurement of L929 cellular spontaneous and synchronous oscillation

        Marimuthu, Mohana,Park, Cheolsoo,Kim, Sanghyo,Choi, Cheol Soo Dove Medical Press 2012 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.7 No.-

        <P>Nonexcitable cell types, fibroblasts of heart muscle or astrocytes, are well known for their spontaneous Ca<SUP>2+</SUP> oscillations. On the other hand, murine fibroblast (L929) cells are known to be deficient in cell–cell adhesive proteins and therefore lack gap junctions for cellular communication. However, these cells exhibit a unique property of collectively synchronized and spontaneous oscillation, as revealed by real-time monitoring of cells cultured on a 250-μm diameter microelectrode for more than 3 days using an electrical cell-substrate impedance-sensing system (ECIS). Live-cell imaging is a widely used technique for oscillation detection, but it has limitations relating to cellular physiological environment maintenance for microscopic analysis and for prolonged periods of study. The present research emphasizes an electrical-sensing technique (ECIS) capable of overcoming the most important issues inherent in live-cell imaging systems for the detection of L929 cellular spontaneous and synchronized oscillation in real-time for longer periods. Possible mechanisms involved in L929 oscillation were elucidated to be periodic extension/contraction of lamellipodia continued as blebbing, which is produced by signals from the actomyosin complex initiated by connexin hemichannel opening and adenosine triphosphate (ATP) release. By applying the connexin hemichannel inhibitor, flufenamic acid, the hindrance of ATP release and calcium transients were analyzed to elucidate this hypothesis.</P>

      • Nanomechanics of Biomolecules: A Review

        백유진,Mohana Marimuthu,김상효 한국바이오칩학회 2008 BioChip Journal Vol.2 No.4

        Nowadays it is possible to manipulate biopolymers such as DNA and protein, in ways to observe at single molecule level, as well as to touch and move, stretch, and crush individual molecules. An increasing number of inter and intramolecular interactions can be probed using single molecule manipulation techniques. Apart from inter- and intra-molecular interactions, the charged molecules interaction with substrates plays a vital role in designing nanobiosensors. Furthermore, the nanomechanical response which is the bending motion via changes of the surface stress produced due to biomolecular interactions over the surface of cantilever has also been studied interestingly by researchers. This review article exemplifies nanomechanical approaches in the analysis of viral packaging, biomolecular interactions, protein folding and unfolding, and DNA sequencing, illustrating how biomolecules contributes to the potential of exploiting novel concepts in technological innovation.

      • SCIESCOPUS
      • Dual drug-loaded nanoparticles on self-integrated scaffold for controlled delivery

        Bennet, Devasier,Marimuthu, Mohana,Kim, Sanghyo,An, Jeongho Dove Medical Press 2012 International journal of nanomedicine Vol.7 No.-

        <P>Antioxidant (quercetin) and hypoglycemic (voglibose) drug-loaded poly-D,L-lactideco-glycolide nanoparticles were successfully synthesized using the solvent evaporation method. The dual drug-loaded nanoparticles were incorporated into a scaffold film using a solvent casting method, creating a controlled transdermal drug-delivery system. Key features of the film formulation were achieved utilizing several ratios of excipients, including polyvinyl alcohol, polyethylene glycol, hyaluronic acid, xylitol, and alginate. The scaffold film showed superior encapsulation capability and swelling properties, with various potential applications, eg, the treatment of diabetes-associated complications. Structural and light scattering characterization confirmed a spherical shape and a mean particle size distribution of 41.3 nm for nanoparticles in the scaffold film. Spectroscopy revealed a stable polymer structure before and after encapsulation. The thermoresponsive swelling properties of the film were evaluated according to temperature and pH. Scaffold films incorporating dual drug-loaded nanoparticles showed remarkably high thermoresponsivity, cell compatibility, and ex vivo drug-release behavior. In addition, the hybrid film formulation showed enhanced cell adhesion and proliferation. These dual drug-loaded nanoparticles incorporated into a scaffold film may be promising for development into a transdermal drug-delivery system.</P>

      • KCI등재

        Nanomechanics of biomolecules: focus on DNA

        Y. Eugene Pak,김대식,Mohana Marimuthu,김상효 대한기계학회 2009 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.23 No.7

        Nano-mechanical measurements and manipulations at the single-cell and single-molecular levels using the atomic force microscope (AFM) and optical tweezers are presenting fascinating opportunities to the researchers in bioscience and biotechnology. Single molecule biophysics technologies, due to their capability to detect transient states of molecules and biomolecular complexes, are the methods of choice for studies in DNA structure and dynamics, DNA-DNA and DNA-protein interactions, and viral DNA packaging. The aim of this review is to describe the recent developments of scientific tools and the knowledge gained in single molecule DNA mechanics such as DNA elasticity, electrostatics, condensation and interactions of DNA with surrounding fluids during its hydrodynamic flow.

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