Gil-Sung Kim

Nanowire Substrate-based Laser Scanning Cytometry for Quantitation of Circulating Tumor Cells

We report on the development of a nanowire substrate-enabled laser scanning imaging cytometry for rare cell analysis in order to achieve quantitative, automated, and functional evaluation of circulating tumor cells. Immuno-functionalized nanowire arrays have been demonstrated as a superior material to capture rare cells from heterogeneous cell populations. The laser scanning cytometry method enables large-area, automated quantitation of captured cells and rapid evaluation of functional cellular parameters (e.g., size, shape, and signaling protein) at the single-cell level. This integrated platform was first tested for capture and quantitation of human lung carcinoma cells from a mixture of tumor cells and leukocytes. We further applied it to the analysis of rare tumor cells spiked in fresh human whole blood (several cells per mL) that emulate metastatic cancer patient blood and demonstrated the potential of this technology for analyzing circulating tumor cells in the clinical settings. Using a high-content image analysis algorithm, cellular morphometric parameters and fluorescence intensities can be rapidly quantitated in an automated, unbiased, and standardized manner. Together, this approach enables informative characterization of captured cells in situ and potentially allows for subclassification of circulating tumor cells, a key step toward the identification of true metastasis-initiating cells. Thus, this nanoenabled platform holds great potential for studying the biology of rare tumor cells and for differential diagnosis of cancer progression and metastasis.

Effect of annealing temperature on structural and bonded states of titanate nanotube films

A conversion from commercial titania (TiO2) nanoparticles to nanotubes was achieved by a hydrothermal method. The titanate nanotube (titanate) film was then deposited on a Si (001) substrate using an electrophoretic deposition (EPD) technique. The post hydrothermal treatment was then carried out by annealing the films at 300–1000°C for 30min in the static air. A major amount of intercalated sodium (Na) in as-synthesized titanate nanotubes was removed during the electrodeposition process. The collapse of the tubular structure can be seen clearly when annealed above 500°C. X-ray diffraction data indicate a significant increase in the anatase phase peak intensity with annealing temperature. O 1s peak is found to be built up of subpeaks of H2O, −OH, and Ti–O. Annealing results in an increase of the Ti–O peak intensity while other peaks disappear. Clear changes in the O 1s peak positions, symmetry, and shift towards lower energy (0.8eV) are evident with the increasing annealing temperature. The doublet spectra...

A quartz nanopillar hemocytometer for high-yield separation and counting of CD4+ T lymphocytes

We report the development of a novel quartz nanopillar (QNP) array cell separation system capable of selectively capturing and isolating a single cell population including primary CD4(+) T lymphocytes from the whole pool of splenocytes. Integrated with a photolithographically patterned hemocytometer structure, the streptavidin (STR)-functionalized-QNP (STR-QNP) arrays allow for direct quantitation of captured cells using high content imaging. This technology exhibits an excellent separation yield (efficiency) of ~95.3 ± 1.1% for the CD4(+) T lymphocytes from the mouse splenocyte suspensions and good linear response for quantitating captured CD4(+) T-lymphoblasts, which is comparable to flow cytometry and outperforms any non-nanostructured surface capture techniques, i.e. cell panning. This nanopillar hemocytometer represents a simple, yet efficient cell capture and counting technology and may find immediate applications for diagnosis and immune monitoring in the point-of-care setting.

Cell adhesion and migration on nanopatterned substrates and their effects on cell-capture yield

With scanning electron microscopy analysis, we investigated the role of nanoscale topography on cellular activities; e.g. cell adhesion and spreading by culturing A549 cells (human lung carcinoma cell line cells) for 1-48 h on three sets of nanostructures; quartz nanopillars (QNPs), silicon nanopillars and silicon nanowire (SiNW) arrays, along with planar glass substrates. We found that cells on QNP arrays developed a longer shape than those on SiNW arrays. In addition, we studied how cell morphologies influence the cell-capture yield on the three sets of nanostructures. This research showed that the filopodial formations were directing the cell-capture yield on nanostructured substrates. This finding implies the possibility of using nanoscale topography features to control the filopodial formation including extension and migration from the cells. Using streptavidin-functionalized SiNW substrate, we further demonstrated a substantially higher yield (~91.8 ± 5.9%) than the planar glass wafers (~24.1 ± 7.5%) in the range of 200-3000 cells.

Specific rare cell capture using micro-patterned silicon nanowire platform

We report on the rapid and direct quantification of specific cell captures using a micro-patterned streptavidin (STR)-functionalized silicon nanowire (SiNW) platform, which was prepared by Ag-assisted wet chemical etching and a photo-lithography process. This platform operates by high-affinity cell capture rendered by the combination of antibody-epithelial cell surface-binding, biotin-streptavidin binding, and the topologically enhanced cell-substrate interaction on a 3-dimensional SiNWs array. In this work, we developed a micro-patterned nanowire platform, with which we were able to directly evaluate the performance enhancement due to nanotopography. An excellent capture efficiency of ~96.6±6.7%, which is the highest value achieved thus far for the targeting specific A549 cells on a selective area of patterned SiNWs, is demonstrated. Direct comparison between the nanowire region and the planar region on the same substrate indicates dramatically elevated cell-capture efficiency on nanotopological surface identical surface chemistry (<2% cell-capture efficiency). An excellent linear response was seen for quantifying captured A549 cells with respect to loaded cells. This study suggests that the micro-patterned STR-functionalized SiNWs platform provides additional advantage for detecting rare cells populations in a more quantitative and specific manner.

Thermal conductivity measurements of single-crystalline bismuth nanowires by the four-point-probe 3-ω technique at low temperatures

We have successfully investigated the thermal conductivity (κ) of single-crystalline bismuth nanowires (BiNWs) with [110] growth direction, via a straightforward and powerful four-point-probe 3-ω technique in the temperature range 10-280 K. The BiNWs, which are well known as the most effective material for thermoelectric (TE) device applications, were synthesized by compressive thermal stress on a SiO2/Si substrate at 250-270 °C for 10 h. To understand the thermal transport mechanism of BiNWs, we present three kinds of experimental technique as follows, (i) a manipulation of a single BiNW by an Omni-probe in a focused ion beam (FIB), (ii) a suspended bridge structure integrating a four-point-probe chip by micro-fabrication to minimize the thermal loss to the substrate, and (iii) a simple 3-ω technique system setup. We found that the thermal transport of BiNWs is highly affected by boundary scattering of both phonons and electrons as the dominant heat carriers. The thermal conductivity of a single BiNW (d ~ 123 nm) was estimated to be ~2.9 W m(-1) K(-1) at 280 K, implying lower values compared to the thermal conductivity of the bulk (~11 W m(-1) K(-1) at 280 K). It was noted that this reduction in the thermal conductivity of the BiNWs could be due to strongly enhanced phonon-boundary scattering at the surface of the BiNWs. Furthermore, we present temperature-dependent (10-280 K) thermal conductivity of the BiNWs using the 3-ω technique.

Ferromagnetic nickel silicide nanowires for isolating primary CD4+ T lymphocytes

Direct CD4+ T lymphocytes were separated from whole mouse splenocytes using 1-dimensional ferromagnetic nickel silicide nanowires (NiSi NWs). NiSi NWs were prepared by silver-assisted wet chemical etching of silicon and subsequent deposition and annealing of Ni. This method exhibits a separation efficiency of ∼93.5%, which is comparable to that of the state-of-the-art superparamagnetic bead-based cell capture (∼96.8%). Furthermore, this research shows potential for separation of other lymphocytes, B, natural killer and natural killer T cells, and even rare tumor cells simply by changing the biotin-conjugated antibodies.

Electrochemically deposited ruthenium seed layer followed by copper electrochemical plating

Electrochemical deposition of ruthenium as a seed layer was investigated on Ti and TiN as barrier layers for Cu interconnects. The aqueous electrolyte, the N-bridged complex of ruthenium(IV) nitrosyl chloride (RuNC), for ruthenium electrochemical deposition was formed in situ. Electrochemical deposition of copper on the Ru seeded barrier layers was also demonstrated. The chemicals for the acid-bath ruthenium electrochemical deposition were ruthenium(III) chloride hydrate (RuCl 3 .3H 2 O), hydrochloric acid (HCI), sulfamic acid (NH 2 SO 3 H), and polyethylene glycol. The chemicals for the acid-bath copper electrochemical deposition were copper(II) sulfate hydrate (CuSO 4 .5H 2 O), sulfuric acid (H 2 SO 4 ), and polyethylene glycol. Results were analyzed by field-emission scanning electron microscopy, atomic force microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Ru-therford backscattering spectrometry. The Ru thin layer with equiaxial grains <10 nm on blanket Ti substrates were obtained by electrochemical deposition. Electrochemical Cu trench fill was successful on patterned TiN 130 nm 2.5 aspect ratio trenches with Ru as a seed layer.

Hot filament chemical vapour deposition processing of titanate nanotube coatings

In the present paper, we report on the processing of titanate nanotubes using the hot filament chemical vapour deposition (HF-CVD) method to synthesize titania?carbon nanotube?wire composites. The titanate nanotubes are prepared using a chemical route, and then deposited on silicon using an electrodeposition method. The HF-CVD is used to process these coatings at different temperatures in vacuum as well as in different concentrations of hydrogen (H2) and methane (CH4) gas mixtures. The evolutions of the surface and precipitation for various phases have been monitored using different characterization techniques. It is observed that titanate nanotubes start disintegrating above Ts~500??C, and exhibit different types of phase precipitation depending upon the temperature and gas ambient. Under appropriate conditions, the presence of activated hydrogen and carbon radicals leads to the formation of novel architectures of mixtures of nanophases such as carbide, nonstoichiometric titania, carbon nanotubes, and titania decorated carbon nanowires. The results are discussed in terms of reduction in the thermal reaction barrier due to the presence of atomic hydrogen, and the formation of energetic sites during disintegration of titania nanotubes to facilitate nucleation of nanotube and nanowire structures.

Growth and morphological study of zinc oxide nanoneedles grown on the annealed titanate nanotubes using hydrothermal method

Hydrothermal growth of ZnO on the annealed titanate nanotube films results in the oriented hexagonal-needlelike structures. The size, shape, density, and alignment of ZnO film are significantly affected by annealing temperature and orientation of the beneath titanate layer. It is believed that oxygen and hydrogen vacancies, generated due to dehydration of interlayered OH groups while annealing of the titanate, are responsible for the changes in the morphology of the ZnO. Microscopic observations clearly resolved nanoneedles with the base diameter of ∼150nm and length of ∼5μm with lattice spacing of 0.52nm, indicating single crystalline ZnO and grown along the (0001) direction. A growth model is presented based on the layer-by-layer growth (three-step growth) as a function of growth time (2–6h). Thicknesses of these three steps were found increasing with growth time. The second step (II) of growth exhibits the same feature as that of the first step (I), i.e., bounded with six crystallographic, lower surfac...