Jungyul Park

Microengineered platforms for cell mechanobiology

Mechanical forces play important roles in the regulation of various biological processes at the molecular and cellular level, such as gene expression, adhesion, migration, and cell fate, which are essential to the maintenance of tissue homeostasis. In this review, we discuss emerging bioengineered tools enabled by microscale technologies for studying the roles of mechanical forces in cell biology. In addition to traditional mechanobiology experimental techniques, we review recent advances of microelectromechanical systems (MEMS)-based approaches for cell mechanobiology and discuss how microengineered platforms can be used to generate in vivo-like micromechanical environment in in vitro settings for investigating cellular processes in normal and pathophysiological contexts. These capabilities also have significant implications for mechanical control of cell and tissue development and cell-based regenerative therapies.

Biologically inspired humidity sensor based on three-dimensional photonic crystals

This letter presents a biomimetic humidity sensor inspired by the humidity-dependent color change observed in the cuticle of the Hercules beetle. A thin-film-type humidity sensor with nanoporous structures (three-dimensional photonic crystals) mimicking the spongy multilayer in the beetles was designed and fabricated using the colloidal templating method and a hydrophilic surface treatment. The visible color of the fabricated humidity sensor changes from blue-green to red as the environmental humidity increases. The wavelength of reflected light that is predicted by Bragg’s equation considering the effect of water absorption shows a good agreement with experimental results.

Quantitative evaluation of cardiomyocyte contractility in a 3D microenvironment

Three-dimensional cultures in a microfabricated environment provide in vivo-like conditions for cells, and have been used in a variety of applications in basic and clinical studies. In this study, the contractility of cardiomyocytes in a 3D environment using complex 3D hybrid biopolymer microcantilevers was quantified and compared with that observed in a 2D environment. By measuring the deflections of the microcantilevers with different surfaces and carrying out finite element modeling (FEM) of the focal pressures of the microcantilevers, it was found that the contractile force of high-density cardiomyocytes on 3D grooved surfaces was 65-85% higher than that of cardiomyocytes on flat surfaces. These results were supported by immunostaining, which showed alignment of the cytoskeleton and elongation of the nuclei, as well as by quantitative RT-PCR, which revealed that cells on the grooved surface had experienced sustained stimuli and tighter cell-to-cell interactions.

Design and fabrication of an integrated cell processor for single embryo cell manipulation

This paper presents an integrated cell processor for the automatic handling of individual embryo cells. The integrated processor can perform various functions such as cell transport, isolation, orientation, and immobilization. These functions are indispensable and frequently used for the manipulation of single cells, but can only be carried out by a skillful operator. The purpose of this study was the integration and automation of these functions for effective cell manipulation, using a MEMS approach. The isolation of a cell was performed using polypyrrole (PPy) valves in a microchannel into which cells were transported. The orientation of cells was controlled by electrorotation (ER), and the target cell was immobilized by suction from a microhole. All of these functions were seamlessly realized on a single chip. Excellent experimental results with mouse (B6CBA) embryo cells showed that this device could substitute for routine and cumbersome manual work. It is expected that the integrated chip will contribute significantly to faster and more reliable manipulation of cells.

Concentration gradient generation of multiple chemicals using spatially controlled self-assembly of particles in microchannels

We present a robust microfluidic platform for the stable generation of multiple chemical gradients simultaneously using in situ self-assembly of particles in microchannels. This proposed device enables us to generate stable and reproducible diffusion-based gradients rapidly without convection flow: gradients are stabilized within 5 min and are maintained steady for several hours. Using this device, we demonstrate the dynamic position control of bacteria by introducing the sequential directional change of chemical gradients. Green Fluorescent Protein (GFP)-expressing bacterial cells, allowing quantitative monitoring, show not only tracking motion according to the directional control of chemical gradients, but also the gradual loss of sensitivity when exposed to the sequential attractants because of receptor saturation. In addition, the proposed system can be used to study the preferential chemotaxis assay of bacteria toward multiple chemical sources, since it is possible to produce multiple chemical gradients in the main chamber; aspartate induces the most preferential chemotaxis over galactose and ribose. The microfluidic device can be easily fabricated with a simple and cost effective process based on capillary pressure and evaporation for particle assembly. The assembled particles create uniform porous membranes in microchannels and its porosity can be easily controlled with different size particles. Moreover, the membrane is biocompatible and more robust than hydrogel-based porous membranes. The proposed system is expected to be a useful tool for the characterization of bacterial responses to various chemical sources, screening of bacterial cells, synthetic biology and understanding many cellular activities.

An integrated bio cell processor for single embryo cell manipulation

In this paper, we present a novel integrated bio cell processor to handle individual embryo cells. Its functions are composed of transporting, isolation, orientation, and immobilization of cells. These functions are essential for biomanipulation of single cells, and have been typically carried out by a proficient operator. The purpose of this study is the automation of these functions for effective cell manipulation using a MEMS based bio cell processor. This device is realized with relatively simple design and fabrication process. To transport cells, microfluidic channel is employed. The isolation of a cell is performed by actuation of polypyrrole (PPy) valves. The orientation control of cells is accomplished by dielectrophoresis (DEP). By the suction from the micro-hole, the target embryo cell is immobilized. Experimental results show that this device can substitute the essential but very tiresome and repeatable embryo cell manipulation and contribute significantly to the improvement of speed and success rate of operation by facilitating the cell manipulation. The cell viability test for the device is studied through the distribution of mitochondria in mouse (B6CBA) embryo cells and cultivation of cells for 86 h after cell was manipulated by DEP.

High-throughput microparticle separation using gradient traveling wave dielectrophoresis

This paper describes highly efficient and high-throughput microparticle separation using gradient traveling wave dielectrophoresis (TwDEP) with a multilayered microelectrode design. Although cell separation based on dielectrophoresis is a very useful and versatile method, its throughput is less than that of a commercially available magnetic activated cell sorter (MACS). Further, in TwDEP-based cell sorters, the microdevices must have a large area to achieve high-throughput separation. However, increasing the TwDEP device area, which is critical for achieving throughput, has limitations: the resistance of microelectrodes also increases. In this study, we have successfully developed a novel gradient TwDEP chip with an extremely large area (31 × 25 mm2) using a unique multilayered bus bar design. The proposed bus bar design, which divides four ac input signals into two groups (0° and 270° phases and 90° and 180° phases), makes it possible to maintain low resistance in microelectrodes for TwDEP despite the increase in the device area. In addition, a microelectrode track design with gradually increasing gaps from 10 to 40 µm between the electrodes was introduced; as a result, the TwDEP force and negative DEP force that balance the gravitational force decrease gradually along the microelectrode track. Finally, the microparticles could be trapped at specific locations depending on their physical properties. We demonstrated the feasibility of our suggestion using latex microparticles (3 µm, 6 µm, 10 µm and 20 µm) and showed the potential of high-throughput separation with the TwDEP technique.

Identification and control of a sensorized microgripper for micromanipulation

This paper presents the design and control of a sensorized microgripper using a voice coil motor and a flexure mechanism. To increase the gripping sensitivity, shape design and determination of sensor attachment position are performed using finite element analysis. Empirical models of the microgripper are acquired for the design of position control and gripping force control. By using the identified models, both the perfect tracking controller for position control and the adaptive zero-phase error tracking controller for force control are implemented. The effectiveness of the proposed model-based control methods is verified by experimental studies.

High Current Ionic Diode Using Homogeneously Charged Asymmetric Nanochannel Network Membrane

A high current ionic diode is achieved using an asymmetric nanochannel network membrane (NCNM) constructed by soft lithography and in situ self-assembly of nanoparticles with uniform surface charge. The asymmetric NCNM exhibits high rectified currents without losing a rectification ratio because of its ionic selectivity gradient and differentiated electrical conductance. Asymmetric ionic transport is analyzed with diode-like I-V curves and visualized via fluorescent dyes, which is closely correlated with ionic selectivity and ion distribution according to variation of NCNM geometries.

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor

As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real‐time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene‐C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene‐C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene‐C can be used as safe coating materials for the implantable bladder volume sensor reported previously.