Nanopiezoelectric Devices for Energy Generation Based on ZnO Nanorods/Flexible-Conjugated Copolymer Hybrids Using All Wet-Coating Processes.

In this study, nanopiezoelectric devices based on ZnO nanorod array/conducting polymers are fabricated for wearable power generation application. To replace the inorganic rigid indium-tin oxide (ITO) conducting coating commonly used in the nanogenerator devices, a series of flexible polyaniline-based conducting copolymers underlying the perpendicularly-oriented ZnO nanorod arrays has been synthesized with improved electric conductivity by the copolymerization of aniline and 3,4-ethylenedioxythiophene (EDOT) monomers in order to optimize the piezoelectric current collection efficiency of the devices. It is found that significantly higher conductivity can be obtained by small addition of EDOT monomer into aniline monomer solution using an in-situ oxidative polymerization method for the synthesis of the copolymer coatings. The highest conductivity of aniline-rich copolymer is 65 S/cm, which is 2.5 times higher than that for homopolymer polyaniline coating. Subsequently, perpendicularly-oriented ZnO nanorod arrays are fabricated on the polyaniline-based copolymer substrates via a ZnO nanoparticle seeded hydrothermal fabrication process. The surface morphology, crystallinity, orientation, and crystal size of the synthesized ZnO nanorod arrays are fully examined with various synthesis parameters for copolymer coatings with different monomer compositions. It is found that piezoelectric current generated from the devices is at least five times better for the device with improved electric conductivity of the copolymer and the dense formation of ZnO nanorod arrays on the coating. Therefore, these results demonstrate the advantage of using flexible π-conjugated copolymer films with enhanced conductivity to further improve piezoelectric performance for future wearable energy harvesting application based on all wet chemical coating processes.

Sensing Ability and Formation Criterion of Fluid Supported Lipid Bilayer Coated Graphene Field-Effect Transistors.

Supported lipid bilayers (SLBs) have been widely used to provide native environments for membrane protein studies. In this study, we utilized graphene field-effect transistors (GFETs) coated with a fluid SLB to perform label-free detection of membrane-associated ligand-receptor interactions in their native lipid bilayer environment. It is known that the analyte-binding event needs to occur within the Debye length for it to be significantly sensed by an FET sensor. However, the thickness of a lipid bilayer is around 4-5-nm-thick, which is larger than the Debye length of a solution with physiologically relevant ionic strength. There is thus a question of whether an FET sensor can detect the binding event above the bilayer. In this study, we show how the existence of an SLB can influence the effective detection distance and the formation criterion of a fluid and continuous SLB on a graphene surface. We discovered that the water intercalation between the graphene and the underlying silica substrate hinders the SLB formation but is required for the stable electrical recording by a GFET. To verify the existence of a fluid SLB on graphene, which was previously complicated by the graphene fluorescence quenching effect, we developed a modified fluorescence recovery after photobleaching method. In addition, our results showed that SLB coated GFETs can quantitatively detect ligand binding onto the receptors embedded in the SLBs. The comparison of our experimental data with a theoretical model shows that the contribution of the SLB acyl chain hydrophobic region to the screening effect can be negligible and, therefore, that the effective detection region can extend beyond the SLB.

Numerical Design and Experimental Realization of a PNIPAM-Based Micro Thermosensor.

Stimuli-responsive polymers are capable of responding to external stimuli and therefore have been widely used for sensing. However, such applications are often based on naïve designs and cannot achieve the desired performance. In this study, we created a micro thermosensor with temperature-sensitive poly( N-isopropylacrylamide) (PNIPAM) hydrogel and temperature-insensitive poly(ethylene glycol) diacrylate (PEGDA) hydrogel using stop-flow lithography. The thermosensor is a bihydrogel microparticle consisting of a NIPAM-rich section and a NIPAM-poor section. Since the sensor is similar to a bimetallic strip in structure, its deformation can be easily identified to indicate temperature. To gain better control over the sensor performance, a numerical model capable of predicting the thermal behavior of the sensor was also developed. The model simulated the mass transfer and polymerization reaction during the fabrication process to determine the distributions of PNIPAM and PEGDA in the sensor. The information was then applied to predict the sensor deformation at various temperatures. We have used the model to access the effects of sensor geometry and fabrication temperature on the performance of the sensor. The sensor made under the guidelines from the numerical model has a working range between 16 and 55 °C. Except at very large deformation, the thermal response of the microsensor measured in experiments follows closely the numerical prediction. We believe such a numerical model can also be used for developing other applications involving stimuli-responsive polymers such as shape-evolving microparticles and origami-based microstructures. With the small size, ease of use, low manufacturing cost, good biocompatibility, and broad sensing range near physiological condition, the PNIPAM-based micro thermosensor should have strong potential to be used for bio-related applications and in a confined environment.

Facile fabrication of superporous and biocompatible hydrogel scaffolds for artificial corneal periphery.

Biocompatible and highly porous network hydrogel scaffolds were fabricated for the development of artificial cornea (AC) periphery/skirt that could be used to enhance the long-term retention of the implants. In this study, a series of hydrogel scaffolds for this application was fabricated from the photo-polymerization of a mixture of poly(ethylene glycol) (PEG)- and poloxamer (P407)-based macromer solutions in dichloromethane in which solvent-induced phase separation (SIPS) arose to form scaffolds with macroporous structure and high water content. The overall porosity ranging from 20% to 75% and open/closed pore structure of the hydrogel scaffolds could be finely tuned by varying the ratio of P407/PEG in the macromer solution and solvent type. The total porosity and open-cell structure of the macropores in the synthesized hydrogel scaffolds affected the swelling behavior, dynamic properties such as the storage moduli of the hydrogels as well as their degradation rates. Based on the subcutaneous implantation in rats, superporous hydrogel scaffolds induced the formation of thinner fibrous capsules around the implants and showed less inflammatory reaction, suggesting that the hydrogel scaffolds made from SIPS exhibited good cytocompatibility. The combined results of swelling ratio, porosity, physical strength and subcutaneous implant tests indicated that the superporous hydrogels with porosity >50% showed potentials to be used for cornea periphery application.

Simulations of DNA stretching by flow field in microchannels with complex geometry.

Recently, we have reported the experimental results of DNA stretching by flow field in three microchannels (C. H. Lee and C. C. Hsieh, Biomicrofluidics 7(1), 014109 (2013)) designed specifically for the purpose of preconditioning DNA conformation for easier stretching. The experimental results do not only demonstrate the superiority of the new devices but also provides detailed observation of DNA behavior in complex flow field that was not available before. In this study, we use Brownian dynamics-finite element method (BD-FEM) to simulate DNA behavior in these microchannels, and compare the results against the experiments. Although the hydrodynamic interaction (HI) between DNA segments and between DNA and the device boundaries was not included in the simulations, the simulation results are in fairly good agreement with the experimental data from either the aspect of the single molecule behavior or from the aspect of ensemble averaged properties. The discrepancy between the simulation and the experimental results can be explained by the neglect of HI effect in the simulations. Considering the huge savings on the computational cost from neglecting HI, we conclude that BD-FEM can be used as an efficient and economic designing tool for developing new microfluidic device for DNA manipulation.

A facile approach toward protein-resistant biointerfaces based on photodefinable poly-p-xylylene coating.

A facile and versatile tool is reported that uses a photodefinable polymer, poly(4-benzoyl-p-xylylene-co-p-xylylene) to immobilize antifouling materials, such as poly(ethylene glycol), poly(ethylene glycol) methyl ether methacrylate, dextran, and ethanolamine. This immobilization process requires the polymer's photoactivated carbonyl groups, which can facilitate light-induced molecular crosslinking and can rapidly react via insertion into CH or NH bonds upon photo-illumination at 365 nm. Importantly, the process does not require additional functional groups on the antifouling materials. The immobilized fouling materials were characterized using X-ray photoelectron spectroscopy (XPS) and infrared reflection absorption spectroscopy (IRRAS), and the resulting antifouling properties were examined through protein adsorption studies on fibrinogen and bovine serum albumin at surfaces that were spatially modified using a photomask during the photochemical process. In addition, the adsorbed fibrinogen was quantitatively analyzed using a quartz crystal microbalance (QCM), and the adsorption values were reduced to 32.8 ± 4.9 ng cm(-2), 5.5 ± 3.9 ng cm(-2), 21.4 ± 4.5 ng cm(-2), and 16.9 ± 3.4 ng cm(-2) for poly(ethylene glycol) (PEG), poly(ethylene glycol) methyl ether methacrylate (PEGMA), dextran, and ethanolamine, respectively. Finally, this antifouling modification technology was demonstrated on an unconventional substrate for a stent that was modified by PEGMA at selected areas using a microscopic patterning technique during photoimmobilization. Low levels of fibrinogen and BSA adsorption were also observed at the areas where PEGMA was attached.

Vapor-based tri-functional coatings.

The tri-functional coating synthesized via CVD copolymerization is comprised of distinguished anchoring sites of acetylene, maleimide, and ketone that can synergically undergo specific conjugation reactions to render surfaces with distinct biological functions, simultaneously. In addition, these tri-functional coatings can be fabricated in a micro-structured fashion on non-conventional surfaces.

Stretching DNA by electric field and flow field in microfluidic devices: An experimental validation to the devices designed with computer simulations.

We examined the performance of three microfluidic devices for stretching DNA. The first device is a microchannel with a contraction, and the remaining two are the modifications to the first. The modified designs were made with the help of computer simulations [C. C. Hsieh and T. H. Lin, Biomicrofluidics 5(4), 044106 (2011) and C. C. Hsieh, T. H. Lin, and C. D. Huang, Biomicrofluidics 6, 044105 (2012)] and they were optimized for operating with electric field. In our experiments, we first used DC electric field to stretch DNA. However, the experimental results were not even in qualitative agreement with our simulations. More detailed investigation revealed that DNA molecules adopt a globular conformation in high DC field and therefore become more difficult to stretch. Owing to the similarity between flow field and electric field, we turned to use flow field to stretch DNA with the same devices. The evolution patterns of DNA conformation in flow field were found qualitatively the same as our prediction based on electric field. We analyzed the maximum values, the evolution and the distributions of DNA extension at different Deborah number in each device. We found that the shear and the hydrodynamic interaction have significant influence on the performance of the devices.

Vapor-deposited parylene photoresist: a multipotent approach toward chemically and topographically defined biointerfaces.

Poly(4-benzoyl-p-xylylene-co-p-xylylene), a biologically compatible photoreactive polymer belonging to the parylene family, can be deposited using a chemical vapor deposition (CVD) polymerization process on a wide range of substrates. This study discovered that the solvent stability of poly(4-benzoyl-p-xylylene-co-p-xylylene) in acetone is significantly increased when exposed to approximately 365 nm of UV irradiation, because of the cross-linking of benzophenone side chains with adjacent molecules. This discovery makes the photodefinable polymer a powerful tool for use as a negative photoresist for surface microstructuring and biointerface engineering purposes. The polymer is extensively characterized using infrared reflection adsorption spectroscopy (IRRAS), scanning electron microscopy (SEM), and imaging ellipsometry. Furthermore, the vapor-based polymer coating process provides access to substrates with unconventional and complex three-dimensional (3D) geometries, as compared to conventional spin-coated resists that are limited to flat 2D assemblies. Moreover, this photoresist technology is seamlessly integrated with other functionalized parylenes including aldehyde-, acetylene-, and amine-functionalized parylenes to create unique surface microstructures that are chemically and topographically defined. The photopatterning and immobilization protocols described in this paper represent an approach that avoids contact between harmful substances (such as solvents and irradiations) and sensitive biomolecules. Finally, multiple biomolecules on planar substrates, as well as on unconventional 3D substrates (e.g., stents), are presented.

Simulation guided design of a microfluidic device for electrophoretic stretching of DNA.

We have used Brownian dynamics-finite element method (BD-FEM) to guide the optimization of a microfluidic device designed to stretch DNA for gene mapping. The original design was proposed in our previous study [C. C. Hsieh and T. H. Lin, Biomicrofluidics 5(4), 044106 (2011)] for demonstrating a new pre-conditioning strategy to facilitate DNA stretching through a microcontraction using electrophoresis. In this study, we examine the efficiency of the original device for stretching DNA with different sizes ranging from 48.5 kbp (λ-DNA) to 166 kbp (T4-DNA). The efficiency of the device is found to deteriorate with increasing DNA molecular weight. The cause of the efficiency loss is determined by BD-FEM, and a modified design is proposed by drawing an analogy between an electric field and a potential flow. The modified device does not only regain the efficiency for stretching large DNA but also outperforms the original device for stretching small DNA.

Simulation of conformational preconditioning strategies for electrophoretic stretching of DNA in a microcontraction.

We have used Brownian dynamics-finite element method to examine two conformational preconditioning approaches for improving DNA stretching in a microcontraction for the purpose of direct gene analysis. The newly proposed "pre-stretching" strategy is found to significantly improve the degree of DNA extension at the exit of the contraction. On the other hand, applying an oscillating extensional field to DNA yields no preconditioning effect. Detailed analysis of the evolution of DNA extension and conformation reveals that the success of our "pre-stretching" strategy relies on the "non-local" effect that cannot be predicted using simple kinematics analysis. In other words, accurate prediction can only be obtained using detailed simulations. Comparing to the existing preconditioning strategies, our "pre-stretching" method is easy to implement while still providing a very good performance. We hope that the insight gained from this study can be useful for future design of biomicrofluidic devices for DNA manipulation.

Ionic effects on the equilibrium dynamics of DNA confined in nanoslits.

The ionic effects on the dynamics and conformation of DNA in silt-like confinement are investigated. Confined lambda-DNA is considered as a model polyelectrolyte, and its longest relaxation time, diffusivity, and size are measured at a physiological ionic strength between 1.7-170 mM. DNA properties change drastically in response to the varying ionic environment, and these changes can be explained by blob theory with an electrostatically mediated effective diameter and persistence length. In the ionic range we investigate, the effective diameter of DNA that represents the electrostatic repulsion between remote segments is found to be the main driving force for the observed change in DNA properties. Our results are useful for understanding the manipulation of biomolecules in nanofluidic devices.

Brownian dynamics simulations with stiff finitely extensible nonlinear elastic-Fraenkel springs as approximations to rods in bead-rod models.

A very stiff finitely extensible nonlinear elastic (FENE)-Fraenkel spring is proposed to replace the rigid rod in the bead-rod model. This allows the adoption of a fast predictor-corrector method so that large time steps can be taken in Brownian dynamics (BD) simulations without over- or understretching the stiff springs. In contrast to the simple bead-rod model, BD simulations with beads and FENE-Fraenkel (FF) springs yield a random-walk configuration at equilibrium. We compare the simulation results of the free-draining bead-FF-spring model with those for the bead-rod model in relaxation, start-up of uniaxial extensional, and simple shear flows, and find that both methods generate nearly identical results. The computational cost per time step for a free-draining BD simulation with the proposed bead-FF-spring model is about twice as high as the traditional bead-rod model with the midpoint algorithm of Liu [J. Chem. Phys. 90, 5826 (1989)]. Nevertheless, computations with the bead-FF-spring model are as efficient as those with the bead-rod model in extensional flow because the former allows larger time steps. Moreover, the Brownian contribution to the stress for the bead-FF-spring model is isotropic and therefore simplifies the calculation of the polymer stresses. In addition, hydrodynamic interaction can more easily be incorporated into the bead-FF-spring model than into the bead-rod model since the metric force arising from the non-Cartesian coordinates used in bead-rod simulations is absent from bead-spring simulations. Finally, with our newly developed bead-FF-spring model, existing computer codes for the bead-spring models can trivially be converted to ones for effective bead-rod simulations merely by replacing the usual FENE or Cohen spring law with a FENE-Fraenkel law, and this convertibility provides a very convenient way to perform multiscale BD simulations.