Jongin Hong

Micro- and nanofluidic systems for high-throughput biological screening.

High-throughput screening (HTS) is a method of scientific experimentation widely used in drug discovery and relevant to the fields of biology. The development of micro- and nanofluidic systems for use in the biological sciences has been driven by a range of fundamental attributes that accompany miniaturization and massively parallel experimentation. We review recent advances in both arraying strategies based on nano/microfluidics and novel nano/microfluidic devices with high analytical throughput rates.

Wetting Characteristics of Insect Wing Surfaces

Biological tiny structures have been observed on many kinds of surfaces such as lotus leaves, which have an effect on the coloration of Morpho butterflies and enhance the hydrophobicity of natural surfaces. We investigated the micro-scale and nano-scale structures on the wing surfaces of insects and found that the hierarchical multiple roughness structures help in enhancing the hydrophobicity. After examining 10 orders and 24 species of flying Pterygotan insects, we found that micro-scale and nano-scale structures typically exist on both the upper and lower wing surfaces of flying insects. The tiny structures such as denticle or setae on the insect wings enhance the hydrophobicity, thereby enabling the wings to be cleaned more easily. And the hydrophobic insect wings undergo a transition from Cassie to Wenzel states at pitch/size ratio of about 20. In order to examine the wetting characteristics on a rough surface, a biomimetic surface with micro-scale pillars is fabricated on a silicon wafer, which exhibits the same behavior as the insect wing, with the Cassie-Wenzel transition occurring consistently around a pitch/width value of 20.

Ultrafast Surface Enhanced Resonance Raman Scattering Detection in Droplet-Based Microfluidic Systems

The development of ultrafast Raman-based detection is one of the most interesting challenges underpinning the application of droplet-based microfluidics. Herein, we describe the use of surface-enhanced resonance Raman spectroscopy (SERRS) with submillisecond time resolution as a powerful detection tool in microdroplet reactors. Individual droplets containing silver nanoparticle aggregates functionalized with Raman reporters are interrogated and characterized by full spectra acquisitions with high spatial resolution in real time. Whereas previous works coupling SERRS with droplet-based microfluidics acquire a single spectrum over single or multiple droplets, we build upon these results by increasing our temporal resolution by 2 orders of magnitude. This allows us to interrogate multiple points within one individual droplet. The SERRS signals emitted from the aggregates are utilized to access the influence of flow rate on droplet size and throughput. Accordingly, our approach allows for high-throughput analysis that facilitates the study of other biological assays or molecular interactions.

AC frequency characteristics of coplanar impedance sensors as design parameters

Glass-based microchannel chips were fabricated using photolithographic technology, and Pt thin-film microelectrodes, as coplanar impedance sensors, were integrated on them. Longitudinal design parameters, such as interelectrode spacing and electrode width, of coplanar impedance sensors were changed to determine AC frequency characteristics as design parameters. Through developing total impedance equations and modeling equivalent circuits, the dominant components in each frequency region were illustrated for coplanar impedance sensors and the measured results were compared with fitted values. As the ionic concentration increased, the value of the frequency-independent region decreased and cut-off frequencies increased. As the interelectrode spacing increased, cut-off frequencies decreased and total impedance increased. However, the width of each frequency-independent region was similar. As the electrode area increased, f(low) decreased but f(high) was fixed. We think that the decrease in R(Sol) dominated over the influence of other components, which resulted in heightening f(low) and f(high). The interelectrode spacing is a more significant parameter than the electrode area in the frequency characteristics of coplanar sensors. The deviation of experimentally obtained results from theoretically predicted values may result from the fringing effect of coplanar electrode structure and parasitic capacitance due to dielectric substrates. We suggest the guidelines of dominant components for sensing as design parameters.

Analysis of protein-protein interactions by using droplet-based microfluidics.

Every little drop: The KD values of angiogenin (ANG) interactions as shown by FRET analysis of thousands of pL‐sized droplets agree with data from bulk‐fluorescence polarization measurements. Importantly, the use of fluorophores does not affect the activity of ANG or the binding of anti‐ANG antibodies to ANG. Such an experimental platform could be applied to the high‐throughput analysis of protein–protein interactions.

Fabrication and investigation of ultrathin, and smooth Pb(Zr,Ti)O3 films for miniaturization of microelectronic devices

Pb(Zr0.52Ti0.48)O3 (PZT) thin films were fabricated on Pt(111)/TiOx/SiO2/Si substrates at 375 °C by radio frequency magnetron sputtering. A mixture of (110) and (100) orientations was found in all the PZT thin films. However, the in-plane grain size increased with an increase in film thickness, all films had smooth surfaces, and the root mean square roughness of the PZT films was in the range of 1–1.5 nm. As the film thickness increased, a decrease in residual stress and volume density of the PZT films was observed. PZT films become poorly crystallized with a decrease in film thickness. The magnitude of the maximum displacement from atomic force microscopy in local piezoresponse hysteresis mode increased from 187.25±9.363 in 40 nm to 418.5±20.925 in 152 nm. We suggest that the degradation in piezoelectric properties with a decrease in film thickness resulted from degradation of the crystallinity observed using transmission electron microscopy analysis, size effects derived from the grain size, and the res...

Bio-electrospraying and droplet-based microfluidics: control of cell numbers within living residues

Bio-electrospraying (BES) has demonstrated great promise as a rapidly evolving strategy for tissue engineering and regenerative biology/medicine. Since its discovery in 2005, many studies have confirmed that cells (immortalized, primary and stem cells) and whole organisms (Danio rerio, Xenopus tropicalis, Caenorhabditis elegans to Drosophila) remain viable post-bio-electrospraying. Although this bio-protocol has achieved much, it suffers from one crucial problem, namely the ability to precisely control the number of cells within droplets and or encapsulations. If overcome, BES has the potential to become a high-efficiency biotechnique for controlled cell encapsulation, a technique most useful for a wide range of applications in biology and medicine ranging from the forming of three-dimensional cultures to an approach for treating diseases such as type I diabetes. In this communication, we address this issue by demonstrating the coupling of BES with droplet-based microfluidics for controlling live cell numbers within droplets and residues.

Controlled aqueous synthesis of ultra-long copper nanowires for stretchable transparent conducting electrode

The environmentally benign synthesis of ultra-long copper nanowires with successful control of diameter and length for stretchable transparent conducting electrodes (TCEs) is reported. Ultra-long copper nanowires (CuNWs) with an average length of 92.5 μm (maximum length up to 260 μm) and an average diameter of 47 nm were synthesized using environmentally friendly water–alcohol mixtures and L-ascorbic acid as a reducing agent. A facile removal of insulating surface layers, such as organic capping molecules and copper oxide/hydroxide, by short-chain organic acid treatment allowed low contact resistance between the CuNWs without post-reductive treatment at elevated temperatures. The CuNWs were directly spray-coated on glass or polydimethylsiloxane (PDMS) at a low processing temperature of 130 °C. The CuNW TCE on a glass substrate exhibited a low sheet resistance of 23.1 Ohm sq−1 and a high optical transmittance of 84.1% at 550 nm. Furthermore, the CuNWs were directly spray-coated on stretchable PDMS, which showed a low sheet resistance of 4.1 Ohm sq−1 and a high optical transmittance of 70% at 550 nm.

A Dielectric Biosensor Using the Capacitance Change with AC Frequency Integrated on Glass Substrates

Glass-based microchannel chips were fabricated using photolithographic technology, and Pt thin-film microelectrodes as dielectric biosensors were integrated on them. From capacitance-frequency measurements at various interelectrode distances and ionic concentrations, a significant difference between deionized (DI) water and tris-ethylenediaminetetraacetic acid (EDTA) (TE) buffer was observed in the low-frequency region. Although the capacitance (CM) of the DI water decreased as the interelectrode distance increased, that of the TE buffer was similar up to a frequency of 100 Hz, after which it was spilt in the same manner as the DI water above 100 Hz. As the ionic concentration increased, the CM of the TE buffer increased and the slope in the low frequency region changed from -0.875 to -0.425. The point where the slope changed shifted towards the frequency increase. These observations were clarified from the viewpoint of interfacial phenomena, such as the electrical double layer and Faradaic reactions, the dielectric constant related to conductivity, and the capacitance inversely proportional to the interelectrode distance. The addition of deoxyribonucleic acid (DNA) molecules (10 ng/µl) increased the capacitance and dielectric loss in the TE buffer at low frequency. It is feasible to use dielectric properties for the rapid and direct detection of biomolecules, particularly DNA molecules, without using labels or indicators.

In vitro biosynthesis of metal nanoparticles in microdroplets.

We report the use of a hydrogel polymer, recombinant Escherichia coli cell extracts, and a microdroplet-based microfluidic device to fabricate artificial cellular bioreactors which act as reactors to synthesize diverse metal nanoparticles (NPs). The combination of cell extracts, microdroplet-based microfluidic device, and hydrogel was able to produce a mass amount of artificial cellular bioreactors with uniform size and shape. For the first time, we report the alternating generation of microdroplets through one orifice for the fabrication of the artificial cellular reactors using the cell extract as inner cellular components and hydrogel as an artificial cellular membrane. Notably, the hydrogels were able to protect the encapsulated cell extracts from the surrounding environment and maintain the functionality of cellular component for the further cellular bioreactor applications. Furthermore, the successful applications of the fabricated artificial cellular bioreactors to synthesize various NPs including quantum dots, iron, and gold was demonstrated. By employing this microfluidic technique, the artificial cellular bioreactors could be applicable for the synthesis of diverse metal NPs through simple dipping of the reactors to the metal precursor solutions. Thus, the different size of NPs can be synthesized through controlling the concentration of metal precursors. This artificial cellular bioreactors offer promising abilities to biofriendly ways to synthesis diverse NPs and can be applicable in chemical, biomedical, and bioengineering applications.