Self-detachable UV-curable polymers for open-access microfluidic platforms.

This study presents an ultraviolet (UV)-curable polymer which is applicable to open-access microfluidic platforms. The UV-curable polymer was prepared by mixing trimethylolpropane triacrylate (TMPTA), 1,6-hexanediol diacrylate (HDDA), polyethylene glycol-diacrylate (PEG-DA), and Irgacure 184. The polymer resin is optically transparent before and after UV-assisted curing and showed good biocompatibility when culturing multiple types of cells on the nanopatterned polymer substrate. The polymer has good adhesion with poly(dimethylsiloxane) (PDMS) even under large deformation and showed a low swelling ratio when exposed to water, suggesting a possibility to be used as a substrate for an organ on a chip. Furthermore, because the polymers have controllable hydrolysis ability depending on the composition, long-term 3D cell culture and subsequent biological analysis with harvested cells are possible. The self-detachable synthesized UV-curable polymer may help the advancement of biomedical studies using in vitro cell culture.

Optogenetic neuronal stimulation promotes axon outgrowth and myelination of motor neurons in a three-dimensional motor neuron-Schwann cell coculture model on a microfluidic biochip.

Axonal regeneration and remyelination of peripheral motor neurons (MNs) are critical for restoring neuromuscular motor function after injury or peripheral neuropathy. We examined whether optogenetically mediated light stimulation (OMLS) could enhance the axon outgrowth and myelination of MNs using three-dimensional motor neuron-Schwann cell (MN-SC) coculture on a microfluidic biochip. The biochip was designed to allow SCs to interact with the axons of MNs, while preventing direct contact between SCs and the cell bodies of MNs. Following coculture with SCs on the microfluidic biochip, MNs were transfected with a light-sensitive channelrhodopsin gene. Transfected MNs subjected to repeated light stimulation (20 Hz, 1 hr) produced significantly longer axons than nontransfected MNs. OMLS of MNs greatly increased the number of myelin basic protein (MBP)-expressing SCs, promoting the initiation of myelination of MNs. Ultrastructurally, OMLS of MNs markedly enhanced the thickness of the compact myelin sheath around the MN axons such that the average thickness was closer to that of the theoretical estimates in vivo. Thus, the MN-SC coculture model on a microfluidic biochip augmented by OMLS of MNs is a feasible platform for studying the relationship of neuronal activity with regrowth and remyelination.

Magnetic Nanoparticle-Embedded Hydrogel Sheet with a Groove Pattern for Wound Healing Application.

Endothelial progenitor cells (EPCs) can induce a pro-angiogenic response during tissue repair. Recently, EPC transplantations have been widely investigated in wound healing applications. To maximize the healing efficacy by EPCs, a unique scaffold design that allows cell retention and function would be desirable for in situ delivery. Herein, we fabricated an alginate/poly-l-ornithine/gelatin (alginate-PLO-gelatin) hydrogel sheet with a groove pattern for use as a cell delivery platform. In addition, we demonstrate the topographical modification of the hydrogel sheet surface with a groove pattern to modulate cell proliferation, alignment, and elongation. We report that the patterned substrate prompted morphological changes of endothelial cells, increased cell-cell interaction, and resulted in the active secretion of growth factors such as PDGF-BB. Additionally, we incorporated magnetic nanoparticles (MNPs) into the patterned hydrogel sheet for the magnetic field-induced transfer of cell-seeded hydrogel sheets. As a result, enhanced wound healing was observed via efficient transplantation of the EPCs with an MNP-embedded patterned hydrogel sheet (MPS). Finally, enhanced vascularization and dermal wound repair were observed with EPC seeded MPS.

Design rules for a tunable merged-tip microneedle.

This publication proposes the use of an elasto-capillarity-driven self-assembly for fabricating a microscale merged-tip structure out of a variety of biocompatible UV-curable polymers for use as a microneedle platform. In addition, the novel merged-tip microstructure constitutes a new class of microneedles, which incorporates the convergence of biocompatible polymer micropillars, leading to the formation of a sharp tip and an open cavity capable of both liquid trapping and volume control. When combined with biocompatible photopolymer micropillar arrays fabricated with photolithography, elasto-capillarity-driven self-assembly provides a means for producing a complex microneedle-like structure without the use of micromolding or micromachining. This publication also explores and defines the design rules by which several fabrication aspects, such as micropillar dimensions, shapes, pattern array configurations, and materials, can be manipulated to produce a customizable microneedle array with controllable cavity volumes, fracture points, and merge profiles. In addition, the incorporation of a modular through-hole micropore membrane base was also investigated as a method for constitutive payload delivery and fluid-sampling functionalities. The flexibility and fabrication simplicity of the merged-tip microneedle platform holds promise in transdermal drug delivery applications.

"Open-top" microfluidic device for in vitro three-dimensional capillary beds.

We introduce a novel microfluidic device to co-culture a blood vessel network and cell tissues in an in vivo-like niche. Our "open-top" microfluidic device is composed of microchannels with micropores in the ceiling, which provides direct fluid access from reservoir to microchannel. Fluid connections through micropores afford novel advantages, including: i) the long-term culture of large-scale microvessel network, ii) access of different fluids to inner and exterior sides of the microvessel, and iii) co-culturing of the microvessel network and small cell tissue. In this study, we have successfully assembled microvessels with 5 mm channel widths. We were also able to mimic capillary bed conditions by co-culturing microvessels with cancer spheroids. Intimate contact between the cancer spheroid and microvessel caused vessel recruitment and an increase in vessel formation, and affected vessel morphology. We expect this device to be used as a novel platform for vascularized tissue models.

A Low Permeability Microfluidic Blood-Brain Barrier Platform with Direct Contact between Perfusable Vascular Network and Astrocytes.

A novel three dimensional blood brain barrier (BBB) platform was developed by independently supplying different types of media to separate cell types within a single device. One channel (vascular channel, VC) is connected to the inner lumen of the vascular network while the other supplies media to the neural cells (neural channel, NC). Compared to co-cultures supplied with only one type of medium (or 1:1 mixture), best barrier properties and viability were obtained with culturing HUVECs with endothelial growth medium (EGM) and neural cells with neurobasal medium supplemented with fetal bovine serum (NBMFBS) independently. The measured vascular network permeability were comparable to reported in vivo values (20 kDa FITC-dextran, 0.45 ± 0.11 × 10-6 cm/s; 70 kDa FITC-dextran, 0.36 ± 0.05 × 10-6 cm/s) and a higher degree of neurovascular interfacing (astrocytic contact with the vascular network, GFAP-CD31 stain overlap) and presence of synapses (stained with synaptophysin). The BBB platform can dependably imitate the perivascular network morphology and synaptic structures characteristic of the NVU. This microfluidic BBB model can find applications in screening pharmaceuticals that target the brain for in neurodegenerative diseases.

Surface energy-tunable iso decyl acrylate based molds for low pressure-nanoimprint lithography.

We presented surface energy-tunable nanoscale molds for unconventional lithography. The mold is highly robust, transparent, has a minimized haze, does not contain additives, and is a non-fluorinated isodecyl acrylate and trimethylolpropane triacrylate based polymer. By changing the mixing ratio of the polymer components, the cross-linking density, mechanical modulus, and surface energy (crucial factors in low pressure ((1-2) × 105 N m-2) low pressure-nanoimprint lithography (LP-NIL)), can be controlled. To verify these properties of the molds, we also characterized the surface energy by measuring the contact angles and calculating the work of adhesion among the wafer, polymer film, and mold for successful demolding in nanoscale structures. Moreover, the molds showed high optical clarity and precisely tunable mechanical and surface properties, capable of replicating sub-100 nm patterns by thermal LP-NIL and UV-NIL.

Rapid large area fabrication of multiscale through-hole membranes.

There are many proposed mechanisms by which single cells can be trapped; among them is the through-hole membrane for the characterization of individual microorganisms. Due to the small scale of the fabricated pores, the construction of through-hole membranes on a large scale and with relatively large areas faces many difficulties. This paper describes novel fabrication methods for a large-area, freestanding micro/nano through-hole membrane constructed from versatile membrane materials using through-hole membranes on a microfluidic chip (THMMC). This process can rapidly (<20 min) fabricate membranes with high fidelity multiscale hole size without residual layers. The through-hole site was easily customizable from the micro to the nanoscale, with a low or high aspect ratio giving rise to reliable membranes. Also, the rigidity and biocompatibility of the through-hole membrane are easily tunable by simple injection of versatile membrane materials to obtain a large area (up to 3600 mm2). Membranes produced in this manner were then applied as a proof of concept for the isolation, cultivation, and quantification of individual micro-algal cells for selection with respect to the growth rate, while controlling the quorum sensing mediated metabolic and proliferative changes.

Ultra-sensitive Pressure sensor based on guided straight mechanical cracks.

Recently, a mechanical crack-based strain sensor with high sensitivity was proposed by producing free cracks via bending metal coated film with a known curvature. To further enhance sensitivity and controllability, a guided crack formation is needed. Herein, we demonstrate such a ultra-sensitive sensor based on the guided formation of straight mechanical cracks. The sensor has patterned holes on the surface of the device, which concentrate the stress near patterned holes leading to generate uniform cracks connecting the holes throughout the surface. We found that such a guided straight crack formation resulted in an exponential dependence of the resistance against the strain, overriding known linear or power law dependences. Consequently, the sensors are highly sensitive to pressure (with a sensitivity of over 1 × 105 at pressures of 8-9.5 kPa range) as well as strain (with a gauge factor of over 2 × 106 at strains of 0-10% range). A new theoretical model for the guided crack system has been suggested to be in a good agreement with experiments. Durability and reproducibility have been also confirmed.

Continuous and scalable fabrication of bioinspired dry adhesives via a roll-to-roll process with modulated ultraviolet-curable resin.

A simple yet scalable strategy for fabricating dry adhesives with mushroom-shaped micropillars is achieved by a combination of the roll-to-roll process and modulated UV-curable elastic poly(urethane acrylate) (e-PUA) resin. The e-PUA combines the major benefits of commercial PUA and poly(dimethylsiloxane) (PDMS). It not only can be cured within a few seconds like commercial PUA but also possesses good mechanical properties comparable to those of PDMS. A roll-type fabrication system equipped with a rollable mold and a UV exposure unit is also developed for the continuous process. By integrating the roll-to-roll process with the e-PUA, dry adhesives with spatulate tips in the form of a thin flexible film can be generated in a highly continuous and scalable manner. The fabricated dry adhesives with mushroom-shaped microstructures exhibit a strong pull-off strength of up to ∼38.7 N cm(-2) on the glass surface as well as high durability without any noticeable degradation. Furthermore, an automated substrate transportation system equipped with the dry adhesives can transport a 300 mm Si wafer over 10,000 repeating cycles with high accuracy.

Efficiency improvement of organic solar cells by tuning hole transport layer with germanium oxide.

Improving optical property is critical for optimizing the power conversion efficiency of organic solar cells. In the present research, we show that modification of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) layer with GeO2 leads to 15% improvement of power conversion efficiency in a polymer solar cells through enhancement of short circuit currents. Modified PEDOT:PSS layer with optimized concentration of GeO2 assists active layer absorbing much light by playing a role of optical spacer. Using AFM and grazing incidence X-ray diffraction (GIXD) data, we also present the evidence that an addition of GeO2 does not affect crystallinity of active layer.

Fabrication of antireflection and antifogging polymer sheet by partial photopolymerization and dry etching.

We present a simple method to fabricate a polymer optical sheet with antireflection and antifogging properties. The method consists of two consecutive steps: photocross-linking of UV-curable polyurethane acrylate (PUA) resin and reactive ion etching (RIE). During photopolymerization, the cured PUA film is divided into two domains of randomly distributed macromers and oligomers due to a relatively short exposure time of 20 s at ambient conditions. Using the macromer domain as an etch-mask, dry etching was subsequently carried out to remove the oligomer domain, leaving behind a nanoturf surface with tunable roughness. UV-vis spectroscopy measurements demonstrate that transmittance of a nanoturf surface is enhanced up to 92.5% as compared to a flat PUA surface (89.5%). In addition, measurements of contact angle (CA) reveal that the etched surface shows superhydrophilicity with a CA as small as 5 degrees. To seek potential applications, I-V characteristics of a thin film organic solar cell were measured under various testing conditions. It is shown that the efficiency can be increased to 2.9% when a nanoturf film with the surface roughness of 34.73 nm is attached to indium tin oxide (ITO) glass. More importantly, the performance is maintained even in the presence of water owing to superhydrophilic nature of the film.

Spontaneous dewetting-induced residue-free patterning at room temperature.

A lithographic patterning method is presented that is based on dewetting induced by sequential molding under an applied pressure. Because of spontaneous dewetting taking place, the window to be opened is free from any residue and the surface exposure is instantaneously assured. This residue-free patterning can be accomplished without any heating process and surface treatment, irrespective of pattern duty ratio. The residue-free patterning is made possible with the use of a rigiflex mold and a roller that is used to bring about pressure-induced thinning leading to spontaneous dewetting. A necessary condition for the method is that the spreading coefficient of spin-coated liquid be negative. The exposed surface can be utilized as a sacrificial layer for etching of underlying layer and/or thin film deposition in a fabrication of electronic and biological devices.

Wettability-controllable super water- and moderately oil-repellent surface fabricated by wet chemical etching.

A facile fabrication method is presented for a super-repellent surface, in which a silicon wafer is etched with a wet chemical method and treated by a fluorinated self-assembled monolayer. This surface is composed of harshly rough nanostructures and highly dense nanoholes. The contact angle of both water and oil with the surface is larger than 150 degrees. The self-cleaning capability of the surface allows for the removal of sticky powders with glycerin droplet. Any desired part(s) of the super-repellent surface can be turned superamphiphilic by simply exposing the desired part(s) to ultraviolet light.