Pillar-Based Mechanical Induction of an Aggressive Tumorigenic Lung Cancer Cell Model.

Tissue microarchitecture imposes physical constraints to the migration of individual cells. Especially in cancer metastasis, three-dimensional structural barriers within the extracellular matrix are known to affect the migratory behavior of cells, regulating the pathological state of the cells. Here, we employed a culture platform with micropillar arrays of 2 µm diameter and 16 µm pitch (2.16 micropillar) as a mechanical stimulant. Using this platform, we investigated how a long-term culture of A549 human lung carcinoma cells on the (2.16) micropillar-embossed dishes would influence the pathological state of the cell. A549 cells grown on the (2.16) micropillar array with 10 µm height exhibited a significantly elongated morphology and enhanced migration even after the detachment and reattachment, as evidenced in the conventional wound-healing assay, single-cell tracking analysis, and in vivo tumor colonization assays. Moreover, the pillar-induced morphological deformation in nuclei was accompanied by cell-cycle arrest in the S phase, leading to suppressed proliferation. While these marked traits of morphology-migration-proliferation support more aggressive characteristics of metastatic cancer cells, typical indices of epithelial-mesenchymal transition were not found, but instead, remarkable traces of amoeboidal transition were confirmed. Our study also emphasizes the importance of mechanical stimuli from the microenvironment during pathogenesis and how gained traits can be passed onto subsequent generations, ultimately affecting their pathophysiological behavior. Furthermore, this study highlights the potential use of pillar-based mechanical stimuli as an in vitro cell culture strategy to induce more aggressive tumorigenic cancer cell models.

Scratch to sensitize: scratch-induced sensitivity enhancement in semiconductor thin-film sensors.

Semiconductor gas sensors are advantageous in miniaturization and can be used in a wide range of applications, yet consume large power due to high operating temperature. Here we demonstrated the ability of nanoscale scratches produced with mechanical abrasion to enhance the chemical sensitivity of thin-film-type semiconductor sensors. Well-aligned arrays of scratches parallel to the electrical current direction between the source and drain electrodes were made, using typical polishing machines with diamond suspensions, on semiconductor thin films produced with various deposition methods such as atomic layer deposition (ALD), sputtering, and the sol-gel technique. Processing with sharp diamond microparticles left nano-grooves on the surface, together with changes in chemical composition. For all of the tested metal oxide thin films, the introduction of scratches yielded increased quantities of oxygen vacancies and metallic components. Scratched ZnO devices exhibited superior performance even at room temperature, as predicted by a computational simulation that showed increased binding energy of gas molecules on defects. The scratch technique shown in the present study may be used to produce dense arrays of nanometer-scale, chemically functionalized line patterns on substrates larger than a few tens of centimeters with minimum cost, which in turn may be used in a variety of applications including massive arrays of sensors displaying high sensitivity.

Multilayer fabrication of unobtrusive poly(dimethylsiloxane) nanobrush for tunable cell adhesion.

Precise modulation of polymer brush in its thickness and grafting density can cause unexpected cell behaviors and regulated bioactivities. Herein, a nanoscale poly(dimethylsiloxane) (PDMS) brush was employed to use as a controllable material for cell adhesion. Facile fabrication of ultrathin monolayer PDMS nanobrush on an underlying substrate facilitated regaining cell adhesion through long-range cell attractive forces such as the van der Waals forces. We showed that cell adhesion is diminished by increasing the number of nanobrush layers, causing a gradual decrease of the effectiveness of the long-range force. The result demonstrates that ultrathin PDMS nanobrush can either promote or inhibit cell adhesion, which is required for various biomedical fields such as tissue-engineering, anti-fouling coating, and implantable biomaterials and sensors.

Ultrathin Metal Crystals: Growth on Supported Graphene Surfaces and Applications.

Controlled nucleation and growth of metal clusters in metal deposition processes is a long-standing issue for thin-film-based electronic devices. When metal atoms are deposited on solid surfaces, unintended defects sites always lead to a heterogeneous nucleation, resulting in a spatially nonuniform nucleation with irregular growth rates for individual nuclei, resulting in a rough film that requires a thicker film to be deposited to reach the percolation threshold. In the present study, it is shown that substrate-supported graphene promotes the lateral 2D growth of metal atoms on the graphene. Transmission electron microscopy reveals that 2D metallic single crystals are grown epitaxially on supported graphene surfaces while a pristine graphene layer hardly yields any metal nucleation. A surface energy barrier calculation based on density functional theory predicts a suppression of diffusion of metal atoms on electronically perturbed graphene (supported graphene). 2D single Au crystals grown on supported graphene surfaces exhibit unusual near-infrared plasmonic resonance, and the unique 2D growth of metal crystals and self-healing nature of graphene lead to the formation of ultrathin, semitransparent, and biodegradable metallic thin films that could be utilized in various biomedical applications.

Photoactive Poly(3-hexylthiophene) Nanoweb for Optoelectrical Stimulation to Enhance Neurogenesis of Human Stem Cells.

Optoelectrical manipulation has recently gained attention for cellular engineering; however, few material platforms can be used to efficiently regulate stem cell behaviors via optoelectrical stimulation. In this study, we developed nanoweb substrates composed of photoactive polymer poly(3-hexylthiophene) (P3HT) to enhance the neurogenesis of human fetal neural stem cells (hfNSCs) through photo-induced electrical stimulation. METHODS: The photoactive nanoweb substrates were fabricated by self-assembled one-dimensional (1D) P3HT nanostructures (nanofibrils and nanorods). The hfNSCs cultured on the P3HT nanoweb substrates were optically stimulated with a green light (539 nm) and then differentiation of hfNSCs on the substrates with light stimulation was examined. The utility of the nanoweb substrates for optogenetic application was tested with photo-responsive hfNSCs engineered by polymer nanoparticle-mediated transfection of an engineered chimeric opsin variant (C1V1)-encoding gene. RESULTS: The nanoweb substrates provided not only topographical stimulation for activating focal adhesion signaling of hfNSCs, but also generated optoelectrical stimulation via photochemical and charge-transfer reactions upon exposure to 539 nm wavelength light, leading to significantly enhanced neuronal differentiation of hfNSCs. The optoelectrically stimulated hfNSCs exhibited mature neuronal phenotypes with highly extended neurite formation and functional neuron-like electrophysiological features of sodium currents and action potentials. Optoelectrical stimulation with 539 nm light simultaneously activated both C1V1-modified hfNSCs and nanoweb substrates, which upregulated the expression and activation of voltage-gated ion channels in hfNSCs and further increased the effect of photoactive substrates on neuronal differentiation of hfNSCs. CONCLUSION: The photoactive nanoweb substrates developed in this study may serve as platforms for producing stem cell therapeutics with enhanced neurogenesis and neuromodulation via optoelectrical control of stem cells.

"Atomic Force Masking" Induced Formation of Effective Hot Spots along Grain Boundaries of Metal Thin Films.

We present an interesting phenomenon, "atomic force masking", which is the deposition of a few-nanometer-thick gold film on ultrathin low-molecular-weight (LMW) polydimethylsiloxane (PDMS) engineered on a polycrystalline gold thin film, and demonstrated the formation of hot spot based on SERS. The essential principle of this atomic force masking phenomenon is that an LMW PDMS layer on a single crystalline grain of gold thin film would repel gold atoms approaching this region during a second cycle of evaporation, whereas new nucleation and growth of gold atoms would occur on LMW PDMS deposited on grain boundary regions. The nanostructure formed by the atomic force masking, denoted here as "hot spots on grain boundaries" (HOGs), which is consistent with finite-difference time-domain (FDTD) simulation, and the mechanism of atomic force masking were investigated by carrying out systematic experiments, and density functional theory (DFT) calculations were made to carefully explain the related fundamental physics. Also, to highlight the manufacturing advantages of the proposed method, we demonstrated the simple synthesis of a flexible HOG SERS, and we used this substrate in a swabbing test to detect a common pesticide placed on the surface of an apple.

Simple Interface Engineering of Graphene Transistors with Hydrophobizing Stamps.

We demonstrate a simple surface engineering method for fabricating graphene transistors by using hydrophobizing stamps. By simply contact-printing hydrophobizing stamp that is made with polydimethylsiloxane (PDMS) on a standard silicon substrate for a certain contact-time, it was possible to control the contact angle of the substrate and electrical characteristics of the graphene transistors supported on the substrate. Moreover, graphene transistors supported on the engineered silicon substrate showed improved performances, including an increase in carrier mobility and loss of hysteresis. As a proof-of-concept experiment, a simple logic gate operation was demonstrated by connecting a pristine graphene device with an interface-engineered device.

Microscale Soft Patterning for Solution Processable Metal Oxide Thin Film Transistors.

We introduce a microscale soft pattering (MSP) route utilizing contact printing of chemically inert sub-nanometer thick low molecular weight (LMW) poly(dimethylsiloxane) (PDMS) layers. These PDMS layers serve as a release agent layer between the n-type Ohmic metal and metal oxide semiconductors (MOSs) and provide a layer that protects the MOS from water in the surrounding environment. The feasibility of our MSP route was experimentally demonstrated by fabricating solution processable In2O3, IZO, and IGZO TFTs with aluminum (Al), a typical n-type Ohmic metal. We have demonstrated patterning gaps as small as 13 µm. The TFTs fabricated using MSP showed higher field-effect-mobility and lower hysteresis in comparison with those made using conventional photolithography.

Strong hydrophobizer: laterally chemisorbed low-molecular-weight polydimethylsiloxane.

We introduce a siloxane chain-based hydrophobizer that exhibits superior thermal and chemical stability compared to the conventional hydrophobizing silane agent under conditions of over 300 °C and pH 2-13. To demonstrate the capability of the siloxane chain-based hydrophobizer to serve as a highly robust chemical surface modifier, we present two applications: the formation of fine metal nanoparticles with a narrow size distribution by thermal aggregation of a metal thin film and the selective deposition of a ruthenium thin film by atomic layer deposition.

Boron-doped peroxo-zirconium oxide dielectric for high-performance, low-temperature, solution-processed indium oxide thin-film transistor.

We developed a solution-processed indium oxide (In2O3) thin-film transistor (TFT) with a boron-doped peroxo-zirconium (ZrO2:B) dielectric on silicon as well as polyimide substrate at 200 °C, using water as the solvent for the In2O3 precursor. The formation of In2O3 and ZrO2:B films were intensively studied by thermogravimetric differential thermal analysis (TG-DTA), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT IR), high-resolution X-ray diffraction (HR-XRD), and X-ray photoelectron spectroscopy (XPS). Boron was selected as a dopant to make a denser ZrO2 film. The ZrO2:B film effectively blocked the leakage current at 200 °C with high breakdown strength. To evaluate the ZrO2:B film as a gate dielectric, we fabricated In2O3 TFTs on the ZrO2:B dielectrics with silicon substrates and annealed the resulting samples at 200 and 250 °C. The resulting mobilities were 1.25 and 39.3 cm(2)/(V s), respectively. Finally, we realized a flexible In2O3 TFT with the ZrO2:B dielectric on a polyimide substrate at 200 °C, and it successfully operated a switching device with a mobility of 4.01 cm(2)/(V s). Our results suggest that aqueous solution-processed In2O3 TFTs on ZrO2:B dielectrics could potentially be used for low-cost, low-temperature, and high-performance flexible devices.

Effects of solution temperature on solution-processed high-performance metal oxide thin-film transistors.

Herein, we report a novel and easy strategy for fabricating solution-processed metal oxide thin-film transistors by controlling the dielectric constant of H2O through manipulation of the metal precursor solution temperature. As a result, indium zinc oxide (IZO) thin-film transistors (TFTs) fabricated from IZO solution at 4 °C can be operated after annealing at low temperatures (∼250 °C). In contrast, IZO TFTs fabricated from IZO solutions at 25 and 60 °C must be annealed at 275 and 300 °C, respectively. We also found that IZO TFTs fabricated from the IZO precursor solution at 4 °C had the highest mobility of 12.65 cm2/(V s), whereas the IZO TFTs fabricated from IZO precursor solutions at 25 and 60 °C had field-effect mobility of 5.39 and 4.51 cm2/(V s), respectively, after annealing at 350 °C. When the IZO precursor solution is at 4 °C, metal cations such as indium (In3+) and zinc ions (Zn2+) can be fully surrounded by H2O molecules, because of the higher dielectric constant of H2O at lower temperatures. These chemical complexes in the IZO precursor solution at 4 °C are advantageous for thermal hydrolysis and condensation reactions yielding a metal oxide lattice, because of their high potential energies. The IZO TFTs fabricated from the IZO precursor solution at 4 °C had the highest mobility because of the formation of many metal-oxygen-metal (M-O-M) bonds under these conditions. In these bonds, the ns-orbitals of the metal cations overlap each other and form electron conduction pathways. Thus, the formation of a high proportion of M-O-M bonds in the IZO thin films is advantageous for electron conduction, because oxide lattices allow electrons to travel easily through the IZO.

Fabrication of a multidomain and ultrafast-switching liquid crystal alignment layer using contact printing with a poly(dimethylsiloxane) stamp.

A compartmentalized multidomain alignment state of a layer of liquid crystal display is achieved using an ultrathin, highly transparent, and ultrafast-responsive alignment layer fabricated by a simple method. The ultrathin alignment layer consists of a self-assembled oligomer layer of poly(dimethylsiloxane) (PDMS) formed by utilizing the oligomers that diffuse out from a PDMS elastomer stamp during a contact printing process.

Low-temperature, high-performance solution-processed thin-film transistors with peroxo-zirconium oxide dielectric.

We demonstrated solution-processed thin film transistors on a peroxo-zirconium oxide (ZrO(2)) dielectric with a maximum temperature of 350 °C. The formation of ZrO(2) films was investigated by TG-DTA, FT-IR, and XPS analyses at various temperatures. We synthesized a zirconium oxide solution by adding hydrogen peroxide (H(2)O(2)). The H(2)O(2) forms peroxo groups in the ZrO(2) film producing a dense-amorphous phase and a smooth surface film. Because of these characteristics, the ZrO(2) film successfully blocked leakage current even in annealing at 300 °C. Finally, to demonstrate that the ZrO(2) film is dielectric, we fabricated thin-film transistors (TFTs) with a solution-processed channel layer of indium zinc oxide (IZO) on ZrO(2) films at 350 °C. These TFTs had a mobility of 7.21 cm(2)/(V s), a threshold voltage (V(th)) of 3.22 V, and a V(th) shift of 1.6 V under positive gate bias stress.

Delicate modification of poly(dimethylsiloxane) ultrathin film by low-energy ion beam treatment for durable intermediate liquid crystal pretilt angles.

Long-term stability of intermediate liquid crystal pretilt angles on a poly(dimethylsiloxane) (PDMS) ultrathin film grafted onto a surface was realized simply and easily via low-energy ion beam (IB) treatment. The composition and surface energy of the thin film could be controlled by varying the low-energy IB treatment. This treatment results in the permanent chemical modification of the film surface, converting it from organic PDMS to a mixed layer of organic PDMS and inorganic silica. The partial transformation of a PDMS surface gives rise to the control of the pretilt angle via the formation of the inhomogeneous surface and the stabilization of the pretilt angle via the cross-linking reaction of broken chemical bonds through IB irradiation. As a result, a continuous variation of pretilt angles that maintained their initial value with long-term stability was obtained. Thus, the unique chemical transformation of the PDMS surface using IB treatment may allow for the production of durable intermediate liquid crystal pretilt angles.

Vertical alignment of liquid crystals with negative dielectric anisotropy on an inorganic thin film with a hydrophilic surface.

The vertical alignment of liquid crystals having negative dielectric anisotropy on an amorphous silicon oxide (a-SiO(x)) thin film is the consequence of the anisotropic interaction between liquid crystals and a-SiO(x) thin films. To investigate the mechanism of the vertical alignment, we changed the physicochemical characteristics of alignment layers by controlling the composition, since the anisotropic interaction depends on the nature of both liquid crystals and an alignment layer. The variation of composition gives rise to a change in the polarizability, which is a simple measure of induced-dipole strength at the surface of the alignment layer. There is a critical transition point from planar to vertical alignment of liquid crystals, and it is the long-range van der Waals interaction that is responsible for the vertical alignment. The competition between long-range van der Waals interaction and short-range dipolar interaction were investigated and analyzed in terms of the interfacial energy between liquid crystals and an alignment layer.