Li-Hsin Han

EFFECTS OF CHEMICAL COMPOSITION ON THE ELECTRICAL PROPERTIES OF NO-NITRIDED SIO2

The impact of nitrogen (N) concentration and distribution on the electrical and reliability properties of rapid‐thermally NO‐annealed oxides is studied. The use of NO‐annealing of thermally grown SiO2 provides an excellent way to isolate the effects of N, since this method allows for the incorporation of varying N profiles in the oxide without a simultaneous increase in dielectric thickness. Results show that the electrical properties of the dielectric under gate and substrate Fowler–Nordheim injection are highly sensitive to the N profile in the dielectric. While interface endurance (ΔDit) is seen to improve monotonically with increasing N concentrations for both +Vg and −Vg, the same is not observed for charge‐to‐breakdown (QBD) properties. It is found that although QBD improves with NO nitridation under +Vg, it shows a turnaround behavior under −Vg, i.e., for a 10‐s NO‐annealed oxide the QBD value is improved over control oxide while further nitridation is seen to degrade QBD under −Vg. The presence of bulk N and the nonuniform N distribution in the dielectric is responsible for this behavior.The impact of nitrogen (N) concentration and distribution on the electrical and reliability properties of rapid‐thermally NO‐annealed oxides is studied. The use of NO‐annealing of thermally grown SiO2 provides an excellent way to isolate the effects of N, since this method allows for the incorporation of varying N profiles in the oxide without a simultaneous increase in dielectric thickness. Results show that the electrical properties of the dielectric under gate and substrate Fowler–Nordheim injection are highly sensitive to the N profile in the dielectric. While interface endurance (ΔDit) is seen to improve monotonically with increasing N concentrations for both +Vg and −Vg, the same is not observed for charge‐to‐breakdown (QBD) properties. It is found that although QBD improves with NO nitridation under +Vg, it shows a turnaround behavior under −Vg, i.e., for a 10‐s NO‐annealed oxide the QBD value is improved over control oxide while further nitridation is seen to degrade QBD under −Vg. The presence of...

Degradation of oxynitride gate dielectric reliability due to boron diffusion

In this letter, we report on the impact of the suppression of boron diffusion via nitridation of SiO2 on gate oxide integrity and device reliability. SiO2 subjected to rapid thermal nitridation in pure nitric oxide (NO) is used to fabricate thin oxynitride gate dielectrics. Both n+ polycrystalline silicon (polysilicon) gated n‐MOS (metal–oxide semiconductor) and p+‐polysilicon gated p‐MOS devices were subjected to anneals of different times to study the effect of dopant diffusion on gate oxide integrity. As expected, an advanced oxynitride gate dielectric will effectively alleviate the boron‐penetration‐induced flatband voltage instability in p+‐polysilicon gated p‐MOS capacitors due to the superior diffusion barrier properties. However, such improvements are observed in conjunction with some degradation of the oxide reliability due to the boron‐blocking/accumulation inside the gate dielectric. Results show that even though the oxide quality is slightly degraded for NO‐nitrided SiO2 with p+‐polysilicon ga...

Projection Microfabrication of Three-Dimensional Scaffolds for Tissue Engineering

This article presents a micromanufacturing method for direct projection printing of threedimensional scaffolds for applications in the field of tissue engineering by using a digital micromirror-array device (DMD) in a layer-by-layer process. Multilayered scaffolds are microfabricated using curable materials through an ultraviolet (UV) photopolymerization process. The prepatterned UV light is projected onto the photocurable polymer solution by creating the “photomask” design with a graphic software. Poly(ethylene glycol) diacrylate is mixed with a small amount of dye 0.3 wt % to enhance the fabrication resolution of the scaffold. The DMD fabrication system is equipped with a purging mechanism to prevent the accumulation of oligomer, which could interfere with the feature resolution of previously polymerized layers. The surfaces of the predesigned multilayered scaffold are covalently conjugated with fibronectin for efficient cellular attachment. Our results show that murine marrow-derived progenitor cells successfully attached to fibronectin-modified scaffolds. DOI: 10.1115/1.2823079

Dynamic tissue engineering scaffolds with stimuli-responsive macroporosity formation

Macropores in tissue engineering scaffolds provide space for vascularization, cell-proliferation and cellular interactions, and is crucial for successful tissue regeneration. Modulating the size and density of macropores may promote desirable cellular processes at different stages of tissue development. Most current techniques for fabricating macroporous scaffolds produce fixed macroporosity and do not allow the control of porosity during cell culture. Most macropore-forming techniques also involve non-physiological conditions, such that cells can only be seeded in a post-fabrication process, which often leads to low cell seeding efficiency and uneven cell distribution. Here we report a process to create dynamic hydrogels as tissue engineering scaffolds with tunable macroporosity using stimuli-responsive porogens of gelatin, alginate and hyaluronic acid, which degrade in response to specific stimuli including temperature, chelating and enzymatic digestion, respectively. SEM imaging confirmed sequential pore formation in response to sequential stimulations: 37 °C on day 0, EDTA on day 7, and hyaluronidase on day 14. Bovine chondrocytes were encapsulated in the Alg porogen, which served as cell-delivery vehicles, and changes in cell viability, proliferation and tissue formation during sequential stimuli treatments were evaluated. Our results showed effective cell release from Alg porogen with high cell viability and markedly increased cell proliferation and spreading throughout the 3D hydrogels. Dynamic pore formation also led to significantly enhanced type II and X collagen production by chondrocytes. This platform provides a valuable tool to create stimuli-responsive scaffolds with dynamic macroporosity for a broad range of tissue engineering applications, and may also be used for fundamental studies to examine cell responses to dynamic niche properties.

Solid freeform fabrication of designer scaffolds of hyaluronic acid for nerve tissue engineering

The field of tissue engineering and regenerative medicine will tremendously benefit from the development of three dimensional scaffolds with defined micro- and macro-architecture that replicate the geometry and chemical composition of native tissues. The current report describes a freeform fabrication technique that permits the development of nerve regeneration scaffolds with precisely engineered architecture that mimics that of native nerve, using the native extracellular matrix component hyaluronic acid (HA). To demonstrate the flexibility of the fabrication system, scaffolds exhibiting different geometries with varying pore shapes, sizes and controlled degradability were fabricated in a layer-by-layer fashion. To promote cell adhesion, scaffolds were covalently functionalized with laminin. This approach offers tremendous spatio-temporal flexibility to create architecturally complex structures such as scaffolds with branched tubes to mimic branched nerves at a plexus. We further demonstrate the ability to create bidirectional gradients within the microfabricated nerve conduits. We believe that combining the biological properties of HA with precise three dimensional micro-architecture could offer a useful platform for the development of a wide range of bioartificial organs.

Large-area patterning of a solution-processable organic semiconductor to reduce parasitic leakage and off currents in thin-film transistors

We describe two techniques for patterning spin-cast thin films of a solution-processable organic semiconductor, triethylsilylethylnyl anthradithiophene (TES ADT), to eliminate parasitic leakage currents and to lower off currents in thin-film transistors. One technique utilizes UV light in the presence of solvent vapors to simultaneously define the active channel and to crystallize TES ADT. The second technique selectively removes TES ADT from the nonchannel regions of the thin-film transistors through direct contact with a poly(dimethylsiloxane) stamp. Both patterning techniques yield thin-film transistors with high charge-carrier mobility (⩾0.1cm2∕Vs), low off currents (10−10–10−11A), and minimal parasitic leakage.

Fabrication of three-dimensional scaffolds for heterogeneous tissue engineering

The development of biomedical scaffolds mimicking a heterogeneous cellular microenvironment for a specified regulation of cell-fates is very promising for tissue engineering. In this study, three-dimensional scaffolds with heterogeneous microstructure were developed using a DMD-PP apparatus. During the fabrication process, this apparatus can efficiently switch monomers to form microstructures with localized, different material properties; the resolution in the arrangement of material properties is comparable to the characteristic size of functional subunits in living organs, namely, a hundred microns. The effectiveness of this DMD-PP apparatus is demonstrated by a woodpile microstructure with heterogeneous fluorescence and also by a microporous cell-culturing scaffold with selected sites for protein adhesion. Cell-cultivation experiment was performed with the microporous scaffold, in which selective cell adhesion was observed.

Photo‐crosslinkable PEG‐Based Microribbons for Forming 3D Macroporous Scaffolds with Decoupled Niche Properties

PEG-based microribbons are designed and fabricated as building blocks for constructing a 3D cell niche with independently tunable biochemical, mechanical, and topographical cues. This platform supports direct cell encapsulation, allows spatial patterning of biochemical cues, and may provide a valuable tool for facilitating the analyses of how interactive niche signaling regulates cell fate in three dimensions.

Modulating polymer chemistry to enhance non-viral gene delivery inside hydrogels with tunable matrix stiffness.

Non-viral gene delivery holds great promise for promoting tissue regeneration, and offers a potentially safer alternative than viral vectors. Great progress has been made to develop biodegradable polymeric vectors for non-viral gene delivery in 2D culture, which generally involves isolating and modifying cells in vitro, followed by subsequent transplantation in vivo. Scaffold-mediated gene delivery may eliminate the need for the multiple-step process in vitro, and allows sustained release of nucleic acids in situ. Hydrogels are widely used tissue engineering scaffolds given their tissue-like water content, injectability and tunable biochemical and biophysical properties. However, previous attempts on developing hydrogel-mediated non-viral gene delivery have generally resulted in low levels of transgene expression inside 3D hydrogels, and increasing hydrogel stiffness further decreased such transfection efficiency. Here we report the development of biodegradable polymeric vectors that led to efficient gene delivery inside poly(ethylene glycol) (PEG)-based hydrogels with tunable matrix stiffness. Photocrosslinkable gelatin was maintained constant in the hydrogel network to allow cell adhesion. We identified a lead biodegradable polymeric vector, E6, which resulted in increased polyplex stability, DNA protection and achieved sustained high levels of transgene expression inside 3D PEG-DMA hydrogels for at least 12 days. Furthermore, we demonstrated that E6-based polyplexes allowed efficient gene delivery inside hydrogels with tunable stiffness ranging from 2 to 175 kPa, with the peak transfection efficiency observed in hydrogels with intermediate stiffness (28 kPa). The reported hydrogel-mediated gene delivery platform using biodegradable polyplexes may serve as a local depot for sustained transgene expression in situ to enhance tissue engineering across broad tissue types.

A facile method to fabricate hydrogels with microchannel-like porosity for tissue engineering.

Hydrogels are widely used as three-dimensional (3D) tissue engineering scaffolds due to their tissue-like water content, as well as their tunable physical and chemical properties. Hydrogel-based scaffolds are generally associated with nanoscale porosity, whereas macroporosity is highly desirable to facilitate nutrient transfer, vascularization, cell proliferation and matrix deposition. Diverse techniques have been developed for introducing macroporosity into hydrogel-based scaffolds. However, most of these methods involve harsh fabrication conditions that are not cell friendly, result in spherical pore structure, and are not amenable for dynamic pore formation. Human tissues contain abundant microchannel-like structures, such as microvascular network and nerve bundles, yet fabricating hydrogels containing microchannel-like pore structures remains a great challenge. To overcome these limitations, here we aim to develop a facile, cell-friendly method for engineering hydrogels with microchannel-like porosity using stimuli-responsive microfibers as porogens. Microfibers with sizes ranging 150-200 μm were fabricated using a coaxial flow of alginate and calcium chloride solution. Microfibers containing human embryonic kidney (HEK) cells were encapsulated within a 3D gelatin hydrogel, and then exposed to ethylenediaminetetraacetic acid (EDTA) solution at varying doses and duration. Scanning electron microscopy confirmed effective dissolution of alginate microfibers after EDTA treatment, leaving well-defined, interconnected microchannel structures within the 3D hydrogels. Upon release from the alginate fibers, HEK cells showed high viability and enhanced colony formation along the luminal surfaces of the microchannels. In contrast, HEK cells in non-EDTA treated control exhibited isolated cells, which remained entrapped in alginate microfibers. Together, our results showed a facile, cell-friendly process for dynamic microchannel formation within hydrogels, which may simultaneously release cells in 3D hydrogels in a spatiotemporally controlled manner. This platform may be adapted to include other cell-friendly stimuli for porogen removal, such as Matrix metalloproteinase-sensitive peptides or photodegradable gels. While we used HEK cells in this study as proof of principle, the concept described in this study may also be used for releasing clinically relevant cell types, such as smooth muscle and endothelial cells that are useful for repairing tissues involving tubular structures.