Taesung Kim

Ulsan National Institute of Science and Technology, Urusan, Ulsan, South Korea

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Publications (21)86.83 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Reporter-gene-based microbial biosensors have high potential for detecting small molecules, including heavy metal ions (HMIs), in a sensitive and selective manner by involving low costs. However, the sensitivity and dynamic range of the sensing mechanism are largely limited by the conventional culture environment that relies on the batch-type addition of the small molecules in nutrients and the subsequent genetic induction of sensing microbes. Here, we describe a high-throughput, chemostat-like microfluidic platform that can continuously supply both nutrients and inducers (HMIs) using microfabricated ratchet structures and a mixing microchannel network. We found that the microfluidic platform not only allowed microbial biosensors to be highly concentrated in a detection microchamber array but also enabled them to continuously grow and control synthetic genetic circuits in response to heavy metals. We also demonstrated that the combination of the platform and microbial biosensors enhanced the sensitivity for detecting divalent lead and cadmium ions by approximately three orders of magnitude relative to conventional batch-type methods. Because the platform is portable and only requires small sample volumes and fluorescent detection, the chemostat-like microfluidic platform in conjunction with microbial biosensors could be widely utilized to facilitate the specific and sensitive detection of molecular analytes on a chip. Copyright © 2014 Elsevier B.V. All rights reserved.
    Biosensors & Bioelectronics 10/2014; 65C:257-264. · 6.45 Impact Factor
  • Mingjie Jia, Taesung Kim
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    ABSTRACT: Microfluidic devices utilize ion concentration polarization (ICP) phenomena for a variety of applications, but a comprehensive understanding on the generation of ICP is still necessary. Recently, the emergence of a novel single channel ICP (SC-ICP) device has stimulated further research on the mechanism of ICP generation, so that we developed a 2-D model of an SC-ICP device that integrates a nanoporous membrane on the bottom surface of the channel, allowing bulk flow over the membrane. We solved a set of coupled governing equations with appropriate boundary conditions to explore ICP numerically. As a result, we not only showed that the simulation results held a strong qualitative agreement with experimental results, but also found the distribution of ion concentrations in the SC-ICP device that has never been reported in previous studies. We confirmed again that the electrophoretic mobility (EPM) of counter-ions in the membrane is the most dominant factor determining the generation and strength of ICP, whereas the charge density of the membrane was dominant to the ICP strength only when a high EPM value was assumed. From the viewpoint of practical applications, an SC-ICP device with a long membrane under low buffer strength showed enhanced performance in the pre-concentration of charged molecules. Therefore, we believe that the simulation results could not only provide sharp insight into ICP phenomena but also predict and optimize the performance of SC-ICP devices in various microfluidic applications.
    Analytical chemistry. 09/2014;
  • Mingjie Jia, Taesung Kim
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    ABSTRACT: Many microfluidic devices have been utilizing ion concentration polarization (ICP) phenomena by using a permselective, nanoporous membrane with electric fields for a variety of pre-concentration applications. However, numerical analyses on the ICP phenomena have not drawn sufficient attention, although they are an intriguing and interdisciplinary research area. In this work, we propose a 2-D model and present numerical simulation results on the ICP, which were obtained by solving three coupled governing equations: Nernst-Planck, Navier-Stokes, and Poisson. With improved boundary conditions and assumptions, we demonstrated that the simulation results are not only consistent with other experimental results but also make it possible to thoroughly understand the ICP phenomena. In addition, we demonstrated that the pre-concentration of analytes can be simulated and quantified in terms of concentration enhancement factors (CEFs) that were related to many factors, such as ionic concentration distribution, electric fields, and flow fields including vortex flows across the membrane. Furthermore, we demonstrated that a high electrophoretic mobility (EPM) of counter-ions in the membrane plays the most important role in producing accurate simulation results while the effect of the charge density of the membrane is relatively insignificant. Hence, it is believed that the model and simulation results would provide good guidelines to better develop microfluidic pre-concentration devices based on the ICP phenomena.
    Analytical chemistry. 07/2014;
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    ABSTRACT: We report a microfluidic device that can rapidly and accurately generate various concentration gradients in a controllable manner for the chemotaxis study of motile bacterial cells by integrating hydrogel into polydimethylsiloxane (PDMS) microchannels. We performed numerical simulations for both the PDMS-sealed hydrogel hybrid device and a representative conventional hydrogel-based device to theoretically compare their characteristics. In addition, we experimentally demonstrated that the PDMS-sealed hydrogel device not only produces various linear and nonlinear concentration gradients without flow-induced shear stresses on motile bacterial cells but also exhibits remarkable advantages over conventional hydrogel-based devices. For example, the PDMS-sealed hydrogel device can be used for fast and accurate generation of various concentration gradients, prevents dehydration of hydrogel and evaporation of solutions, directs diffusion of chemicals such as chemoattractants, exhibits long-term durability, and is easy to handle. Because the hydrogel used is biocompatible and arbitrary concentration profiles can be easily designed and produced on a chip, we believe that not only the PDMS-sealed hydrogel fabrication method but also the versatile concentration gradient generation device can be used for various studies on interaction between chemicals and cells including bacterial chemotaxis assays.
    Microfluidics and Nanofluidics 01/2014; 16(4). · 3.22 Impact Factor
  • Yoonkwang Nam, Minseok Kim, Taesung Kim
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    ABSTRACT: Most polymer-replica-based microfluidic devices are mainly fabricated by using standard soft-lithography technology so that multi-level masters (MLMs) require multiple spin-coatings, mask alignments, exposures, developments, and bakings. In this paper, we describe a simple method for fabricating MLMs for planar microfluidic channels with multi-level barriers (MLBs). A single photomask is necessary for standard photolithography technology to create a polydimethylsiloxane grey-scale photomask (PGSP), which adjusts the total amount of UV absorption in a negative-tone photoresist via a wide range of dye concentrations. Since the PGSP in turn adjusts the degree of cross-linking of the photoresist, this method enables the fabrication of MLMs for an MLB-integrated microfluidic device. Since the PGSP-based soft-lithography technology provides a simple but powerful fabrication method for MLBs in a microfluidic device, we believe that the fabrication method can be widely used for micro total analysis systems that benefit from MLBs. We demonstrate an MLB-integrated microfluidic device that can separate microparticles.
    Journal of Micromechanics and Microengineering 09/2013; 23(10):105015. · 1.79 Impact Factor
  • Minseok Kim, Taesung Kim
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    ABSTRACT: The integration of nanoporous membranes into microfluidic devices allows a wide range of analytical and biochemical applications such as stable concentration gradient generation, sample pre-concentration, and ion and biomolecule filtration in a controllable manner. However, further applications of nanoporous membranes in microfluidic devices require rapid and controllable fabrication methods of various nanoporous precursor materials; currently, few such methods exist. Here, we describe simple and robust methods that can be used for microfabricating four different precursor materials as leakage-tight membranes in a microfluidic channel network. The methods consist of a common integration process and individual solidification processes such as solvent evaporation, UV-curing, and temperature treatment. We demonstrate that the fabricated membranes can be used for electrokinetic, nanofluidic pre-concentration of bio-samples such as proteins, cells, and microspheres on either the anodic or cathodic side of the membranes. In addition, we not only characterize the physicochemical properties of the membranes such as conductance of membrane-integrated microchannels, relative permselectivity, and pre-concentration ability, but also compare fabrication availability, membrane robustness, surface charge density tunability and biocompatibility with buffer solutions. The methods are versatile for many nanoporous precursor materials and easy to control the location and dimension of the membranes. Hence, the methods developed and the characterized properties of the membranes tested in this work could be widely employed for further applications of nanoporous membranes in microfluidic systems.
    The Analyst 08/2013; · 4.23 Impact Factor
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    ABSTRACT: This paper describes a system to study how small physical perturbations can affect bacterial community behavior in unexpected ways through modulation of diffusion and convective transport of chemical communication molecules and resources. A culture environment that mimics the chemically open characteristic of natural bacterial habitats but with user-defined spatio-temporal control of bacteria microcolonies is realized through use of an aqueous two phase system (ATPS). The ATPS is formulated with non-toxic dextran (DEX) and poly(ethylene glycol) (PEG) dissolved in cell culture media. DEX-phase droplets formed within a bulk PEG-phase stably confine the bacteria within it while small molecules diffuse relatively freely. Bacteria-containing DEX droplets can also be magnetically relocated, without loss of its bacterial content, when DEX-conjugated magnetic particles are included. We found that decreasing the distance between quorum-sensing (QS)-coupled microcolonies increased green fluorescent protein (GFP) expression due to increased inter-colony chemical communication but with upper limits. Periodic relocation of the chemical signal receiver colony, however, increased GFP expression beyond these typical bounds predicted by quorum sensing concepts alone by maintaining inter-colony chemical communication while also relieving the colony of short-range resource depletion effects. Computer simulations suggest that such increased productive output in response to periodic non-lethal physical pertubations is a common feature of chemically-activated interactive cell systems where there is also a short-range inhibitory effect. In addition to providing insights on the effect of bacteria relocation, the magnetic ATPS droplet manipulation capability should be broadly useful for bioanalyses applications where selective partitioning at the microscale in fully aqueous conditions are needed.
    Journal of the American Chemical Society 01/2013; · 10.68 Impact Factor
  • Minseok Kim, Mingjie Jia, Taesung Kim
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    ABSTRACT: We describe a novel and simple mechanism for inducing ion concentration polarization (ICP) using a surface-patterned perm-selective nanoporous film like Nafion in single, open microchannels. Such a surface-patterned Nafion film can rapidly transport only cations from the anodic side to the cathodic side through the nanopore clusters so that it is possible to generate an ICP phenomenon near the Nafion film. In this work, we characterize transport phenomena and distributions of ion concentration under various electric fields near the Nafion film and show that single-channel based ICP (SC-ICP) is affected by Nafion film thicknesses, strengths of applied electric fields, and ionic strengths of buffer solutions. We also emphasize that SC-ICP devices have several advantages over previous dual-channel ICP (DC-ICP) devices: easy and simple fabrication processes, inherently leak-tight, simple experimental setup requiring only one pair of electrodes, stable and robust ICP induced rapidly, and low electrical resistances helping to avoid Joule heating, and membrane perm-selectivity breakdown but allowing as high bulk flow as an open, plain microchannel. As an example of applications, we demonstrate that SC-ICP devices not only have high potential in pre-concentrating proteins in massively parallel microchannels but also enable the concentration and lysis of bacterial cells simultaneously and continuously on a chip; therefore, proteins within the cells are extracted, separated from the concentrated cells and then pre-concentrated at a different location that is closer to the Nafion film. Hence, we believe that the SC-ICP devices have higher possibilities of being easily integrated with traditional microfluidic systems for analytical and biotechnological applications.
    The Analyst 01/2013; · 4.23 Impact Factor
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    ABSTRACT: We present a light-switchable gene expression system for both inducible and switchable control of gene expression at a single cell level in Escherichia coli using a previously constructed light-sensing system. The λ cI repressor gene with an LVA degradation tag was expressed under the control of the ompC promoter on the chromosome. The green fluorescent protein (GFP) gene fused to a λ repressor-repressible promoter was used as a reporter. This light-switchable system allows rapid and reversible induction or repression of expression of the target gene at any desired time. This system also ensures homogenous expression across the entire cell population. We also report the design of a miniaturized photobioreactor to be used in combination with the light-switchable gene expression system. The miniaturized photobioreactor helps to reduce unintended induction of the light receptor due to environmental disturbances and allows precise control over the duration of induction. This system would be a good tool for switchable, homogenous, strong, and highly regulatable expression of target genes over a wide range of induction times. Hence, it could be applied to study gene function, optimize metabolic pathways, and control biological systems both spatially and temporally.
    PLoS ONE 01/2013; 8(1):e52382. · 3.53 Impact Factor
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    ABSTRACT: We describe a microfluidic concentrator array device that is integrated with microfabricated ratchet structures to concentrate motile bacterial cells in desired destinations with required cell densities. The device consists of many pairs of concentrators with a wide range of spacing distances on a chip, and allows cells in one concentrator to be physically separated from but chemically connected to cells in the other concentrator. Therefore, the device facilitates quantification of the effect of spacing distance on the cell-to-cell communication of synthetically engineered bacterial cells. In addition, the device enables us to control the cell number density in each concentrator unit by adjusting the concentration time and the density of cell suspensions, and the basic concentrator unit of the device can be repeatedly duplicated on a chip. Hence, the device not only facilitates an investigation of the effect of cell densities on cell-to-cell communication, but it can also be further applied to an investigation of cellular communication among multiple types of cells. Lastly, the device can be easily fabricated using a single-layered soft-lithography technology so that we believe it would provide a simple but robust means for many synthetic and systems biologists to simplify and speed up their investigations of the synthetic genetic circuits in bacterial cells.
    Lab on a Chip 06/2012; 12(20):3914-22. · 5.70 Impact Factor
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    ABSTRACT: We describe a hydrogel patterning and transferring (HPT) method that facilitates the quantitative analysis of synthetically engineered genetic circuits within bacterial cells. The HPT method encapsulates cells in the alginate hydrogel patterns by using polydimethylsiloxane (PDMS) template. Then, the hydrogel-encapsulated cell patterns are transferred onto an agarose hydrogel substrate that encapsulates inducer chemicals or bacterial cells. Using the HPT method, we demonstrate that inducers in the agarose hydrogel substrate regulate gene expression of the patterned cells for qualitative analysis by activating the promoters of fluorescence protein genes. In addition, we demonstrate that the HPT method can be used for the analysis of the cross-talk between genetic circuits and the concentration-dependent gene expression and regulation because the agarose hydrogel substrate can produce concentration gradients of inducers. Lastly, we demonstrate that the HPT method can be applied to investigating intercellular communication between neighboring cells with a wide range of cell densities. Since the HPT method is simple to deal with but versatile and powerful to quantitatively analyze genetic circuits in living cells in many controllable manners, we believe that the method can be widely used for the rapid advancement of synthetic, molecular, and systems biology.
    Biomaterials 01/2012; 33(2):624-33. · 8.31 Impact Factor
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    ABSTRACT: We present a microfabricated concentrator array device that makes it possible to quantify the predation rate of Bdellovibrio bacteriovorus, a predatory microbe, toward its prey, Escherichia coli str. MG1655. The device can accumulate both prey and predator microbes sequentially within a series of concentrator arrays using the motility of the microbes and microfabricated arrowhead-shaped ratchet structures. Since the device can constrain both prey and predator cells within 200 pL chambers at a desired range of cell densities, it was demonstrated that the device cannot only enhance the possibility of studying predation processes/cycles directly at a single cell level but can also quantify the predation rates indirectly by measuring the time-dependent fluorescent intensity signals from the prey. Furthermore, the device can produce a wide range of initial prey to predator density ratios within various concentrator arrays through the use of microfluidic mixer structures on a single array chip, which allows us to study many different conditions with a single set of cultures, and quantitatively characterize the predation behaviour/rate. Lastly, we note that this novel concentrator array device can be a very powerful tool facilitating studies of microbial predations and microbe-microbe interaction and may be broadly used in other microbial biotechnological applications.
    Lab on a Chip 09/2011; 11(17):2916-23. · 5.70 Impact Factor
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    ABSTRACT: We present a novel microfluidic device that enables high sensitive analyses of the chemotactic response of motile bacterial cells (Escherichia coli) that swim toward a preferred nutrient by sorting and concentrating them. The device consists of the Y-shaped microchannel that has been widely used in chemotaxis studies to attract cells toward a high concentration and a concentrator array integrated with arrowhead-shaped ratchet structures beside the main microchannel to trap and accumulate them. Since the number of accumulated cells in the concentrator array continuously increases with time, the device makes it possible to increase the sensitivity of detecting chemotactic responses of the cells about 10 times greater than Y-shaped channel devices in 60 min. In addition, the device can characterize the relative chemotactic sensitivity of chemoreceptors to chemoeffectors by comparing the number of cells in the concentrator array at different distances from the channel junction. Since the device allows the analysis of both the chemotactic responses and the sensitivity of chemoreceptors with high resolution, we believe that not only can the device be broadly used for various microbial chemotaxis assays but it also can further the advancement of microbiology and even synthetic biology.
    The Analyst 06/2011; 136(16):3238-43. · 4.23 Impact Factor
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    ABSTRACT: We utilized a commercially available materials printer to investigate synthetic multicellular cell-to-cell communication because inkjet printing technology makes it easy to print spatiotemporal patterns of soluble biomolecules and live cells. Since cells are genetically programmed to communicate with one another via synthetic biology, cell signaling molecules secreted by one cell microcolony can induce two neighboring cell microcolonies to respond by expressing or stopping the expression of fluorescent protein genes. In this work, we not only characterize the printing parameters such as the initial seeding numbers, spacing distances, microcolony sizes, printing timings, and printed patterns of cells but also demonstrate that the use of the proposed printing technology can provide a useful means for many synthetic biologists to simplify and speed up the investigation of cell-to-cell communication between synthetic bacterial cells.
    Biomaterials 04/2011; 32(10):2500-7. · 8.31 Impact Factor
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    ABSTRACT: Inter-cellular communication via diffusible small molecules is a defining character not only of multicellular forms of life but also of single-celled organisms. A large number of bacterial genes are regulated by the change of chemical milieu mediated by the local population density of its own species or others. The cell density-dependent "autoinducer" molecules regulate the expression of those genes involved in genetic competence, biofilm formation and persistence, virulence, sporulation, bioluminescence, antibiotic production, and many others. Recent innovations in recombinant DNA technology and micro-/nano-fluidics systems render the genetic circuitry responsible for cell-to-cell communication feasible to and malleable via synthetic biological approaches. Here we review the current understanding of the molecular biology of bacterial intercellular communication and the novel experimental protocols and platforms used to investigate this phenomenon. A particular emphasis is given to the genetic regulatory circuits that provide the standard building blocks which constitute the syntax of the biochemical communication network. Thus, this review gives focus to the engineering principles necessary for rewiring bacterial chemo-communication for various applications, ranging from population-level gene expression control to the study of host-pathogen interactions.
    BMB reports 01/2011; 44(1):1-10. · 1.63 Impact Factor
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    ABSTRACT: Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.
    International Journal of Molecular Sciences 01/2011; 12(6):3576-93. · 2.46 Impact Factor
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    ABSTRACT: Using an aqueous two-phase system comprised of dextran and polyethylene glycol, this article describes the stable spatial patterning of sub-microlitre droplets of bacterial suspensions. Microdroplets of different types of bacterial populations are positioned and maintained adjacent to each other without significant dispersion even though the bacteria are in suspension and not surface bound. Small molecules, in contrast, diffuse relatively freely between the two aqueous phases. The usefulness of these capabilities is demonstrated by generating a small array of suspensions containing different Escherichia coli strains engineered to respond fluorescently or luminescently to different chemical stimuli. When a chemical stimulus is presented, this droplet array produces a pattern of bacterial "illumination" that reflects the type of chemical to which the array was exposed.
    The Analyst 11/2010; 135(11):2848-52. · 4.23 Impact Factor
  • Minseok Kim, Taesung Kim
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    ABSTRACT: We present a diffusion-driven and long-range concentration gradient generator that uses hydrogel as a porous membrane to prevent convection flows but allow the diffusion of cell signaling molecules for the study of bacterial chemotaxis in a microfluidic device. Using this device, we characterized the critical concentrations associated with the chemotactic responses of cells that initially created a population band and then migrated in bands in the presence of multiconcentration gradients. In addition, this device can be used to study the preferential chemotaxis of bacterial cells toward different carbon sources: glucose, galactose, and mannose were preferred over arabinose and xylose, in this order. This was possible since the device is able to simultaneously produce long-range concentration gradients of different chemicals as well. The method presented in this study is easy to perform and the device is cheap to fabricate, so that we believe that these characteristics not only make this device a very useful tool to study the chemotaxis of various, motile microorganisms but also permit parallel experimentation and reduce the time and effort needed in characterizing bacterial responses to various chemicals.
    Analytical Chemistry 10/2010; 82(22):9401-9. · 5.82 Impact Factor
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    ABSTRACT: We present a novel microfabricated concentrator for Escherichia coli that can be a stand-alone and self-contained microfluidic device because it utilizes the motility of cells. First of all, we characterize the motility of E. coli cells and various ratcheting structures that can guide cells to move in a desired direction in straight and circular channels. Then, we combine these ratcheting microstructures with the intrinsic tendency of cells to swim on the right side in microchannels to enhance the concentration rates up to 180 fold until the concentrators are fully filled with cells. Furthermore, we demonstrate that cells can be positioned and concentrated with a constant spacing distance on a surface, allowing spatial patterning of motile cells. These results can be applied to biosorption or biosensor devices that are powered by motile cells because they can be highly concentrated without any external mechanical and electrical energy sources. Hence, we believe that the concentrator design holds considerable potential to be applied for concentrating and patterning other motile microbes and providing a versatile structure for motility study of bacterial cells.
    Journal of Micromechanics and Microengineering 08/2010; 20(9):095006. · 1.79 Impact Factor
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    ABSTRACT: Microfabrication technologies have a high potential for novel approaches to access living cells at a cellular or even at a molecular level. In the course of reviewing and discussing the current application of microinterface systems including nanointerfaces to stimulate and analyze cellular responses with subcellular resolution, this article focuses on interfaces based on microfluidics, nanoparticles, and scanning electrochemical microscopy (SECM). Micro/nanointerface systems provide a novel, attractive means for cell study because they are capable of regulating and monitoring cellular signals simultaneously and repeatedly, leading us to an enhanced understanding and interpretation of cellular responses. Therefore, it is hoped that the integrated micro/nanointerfaces presented in this review will contribute to future developments of cell biology and facilitate advanced biomedical applications.
    Annals of Biomedical Engineering 03/2010; 38(6):2056-67. · 3.23 Impact Factor