PDMS Mold Research Articles

Fabrication of Porous Collagen Scaffolds Containing Embedded Channels with Collagen Membrane Linings.

Tissues and organs contain an extracellular matrix (ECM). In the case of blood vessels, endothelium cells are anchored to a specialized basement membrane (BM) embedded inside the interstitial matrix (IM). We introduce a multi-structural collagen-based scaffold with embedded microchannels that mimics in vivo structures within vessels. Our scaffold consists of two parts, each containing two collagen layers, i.e., a 3D porous collagen layer analogous to IM lined with a thin 2D collagen film resembling the BM. Enclosed microchannels were fabricated using contact microprinting. Microchannel test structures with different sizes ranging from 300 to 800 µm were examined for their fabrication reproducibility. The heights and perimeters of the fabricated microchannels were ~20% less than their corresponding values in the replication PDMS mold; however, microchannel widths were significantly closer to their replica dimensions. The stiffness, permeability, and pore size properties of the 2D and 3D collagen layers were measured. The permeability of the 2D collagen film was negligible, making it suitable for mimicking the BM of large blood vessels. A leakage test at various volumetric flow rates applied to the microchannels showed no discharge, thereby verifying the reliability of the proposed integrated 2D/3D collagen parts and the contact printing method used for bonding them in the scaffold. In the future, multi-cell culturing will be performed within the 3D porous collagen and against the 2D membrane inside the microchannel, hence preparing this scaffold for studying a variety of blood vessel-tissue interfaces. Also, thicker collagen scaffold tissues will be fabricated by stacking several layers of the proposed scaffold.

A New Silicon Mold Process for Polydimethylsiloxane Microchannels.

As an alternative to SU-8 soft lithography, a new silicon mold process of fabricating PDMS microchannel chips was proposed. A picosecond laser is used to cut through a 550 μm thick silicon wafer and generate the original microchannel pattern with a 50 μm minimum feature size. This single-crystal silicon pattern, with the edge debris caused by laser cutting being trimmed off by a KOH solution and with the protection field oxide layer being removed by BOE afterwards, firmly resided on a glass substrate through the anodic bonding technique. Four-inch wafers with microchannel patterns as the PDMS mold cores were successfully bonded on Pyrex 7740 or Eagle XG glass substrates for the follow-up PDMS molding/demolding process. This new maskless process does not need a photolithography facility, but the laser cutting service must be provided by professional off-campus companies. One PDMS microchannel chip for particle separation was shown as an example of what can be achieved when using this new process.

Gelatin-PVP dissolving microneedle-mediated therapy for controlled delivery of nifedipine for rapid antihypertension treatment.

Nifedipine has exhibited to be the oldest primary drug having promising therapeutic potential for hypertension, angina pectoris, and pre-eclampsia treatment which are the most emergency serious complications worldwide. Moreover, for long-term treatment transdermal route of delivery using polymeric dissolving microneedles (DMNs) patches has shown greater advantages, thus enhancing treatment compliance, painless, reducing the daily number of doses, prolonged release in a controlled manner, and variable bioavailability making this an ideal candidate for the transdermal therapeutic system. Here, we fabricated DMN patches made of gelatin and PVP using PDMS molds loaded with nifedipine drugs for a controlled painless delivery for a longer stable duration. The prepared gelatin-PVP (gel-PVP) DMN patches loaded with nifedipine were fabricated by centrifugation casting method. The characterization results displayed excellent mechanical strength of the needles to penetrate the skin. SEM and confocal microscopy showed penetration of the needles up to 567-600 µm using rhodamine B applied to the hairless punctured skin site. FTIR study exhibited no degradation of the drug was observed while fabricating the DMNs patch at different pH 7.4 and 4. Skin resealing test proved that there was immediate resealing of the skin observed within 10-15 min. Further in-vitro drug release profile study was carried out by dissolution method at different pH 7.4 and 4 showed sustained release of the drug up to 96 ± 2% till 48-72 h avoiding polymer or drug loss which was quantified by UV vis spectrophotometer at 235 nm absorbance showed stable release of the drug upto 48-72 h. A stability study carried out by the HPLC method showed the DMN patches loaded with the drug were found to be stable for up to 30 days at 25 °C. This novel preliminary data are the first study to our knowledge introducing these fabricated nifedipine gel-PVP DMN patches were found to be very efficient and showed prolonged controlled release up to 48-72 h thereby treating hypertension in a convenient, painless manner. This DMN patch-formulated design might act as a potential approach leading to a controllable, self-administrative, and rapid transdermal delivery system.

A double-sided PDMS mold for double-sided embossing by rollers

A double-sided PDMS mold for double-sided embossing by rollers

High performance photothermal carbon nanotubes/nanostructured hydrogel for solar electricity production and solar water sterilization

Solar energy is a promising renewable energy source with the potential to contribute to sustainable development. Efficient photothermal conversion is critical for solar energy acquisition and conversion. Here, carbon nanotubes (CNTs) were gelatinized to obtain the nanostructured CNT/hydrogel, and then highly light-absorbing CNT/n-hydrogels with surface texture were obtained by replicating the micrometer structure from the black silicon (b-Si) surface onto CNT/hydrogels by using a PDMS mold. Through the synergistic effect of both surface texture and nanostructures, it demonstrates high efficiency of solar electricity production and solar sterilization. A small thermoelectric (TE) module with an area of 4 × 4 cm2 is integrated with CNT/n-hydrogel absorber for the investigation of photo-thermoelectric conversion. The output power of the CNT/n-hydrogel TE device is 1.42 W•m−2 under 1 sun. And by connecting four devices in series, it has successfully demonstrated for charging mobile phones under two different solar illuminations. This work provides a cost-effective and easy fabrication method for opening up the hydrogel as a photothermal absorber, which is low-cost, reproducible, high-efficiency solar water sterilization and high photothermal conversion efficiency.

CARD11: Polymeric Endoluminal Paving for Prevention of Paravalvular Leak in Transcatheter Aortic Valve Replacement

Background: Calcific aortic valve disease and associated aortic stenosis is increasingly common, with prevalence across the age spectrum. Transcatheter aortic valve replacement (TAVR) has emerged as a life-saving, non-surgical alternative for replacement of diseased aortic valves, restoring non-obstructive blood flow from the heart. While effective, current TAVR technology remains limited by adaptability to patient-specific anatomy, leading to incomplete deployment and non-conformal fit resulting in paravalvular leak. Polymeric endoluminal paving was previously developed as a methodology allowing deployment of polymeric materials on tissue surfaces, serving as structural materials and barriers. Here we adapt the paving methodology to fill gaps and defects resulting from incomplete TAVR valve deployment to limit paravalvular leak. Specifically, we assess the efficacy pf polymeric paving in vitro as a means of gap filling and leak reduction in valves deployed in 3-D physical models of severely stenosed aortic valves. We hypothesize that applied polymeric biomaterials will fill and conform to irregular aortic valve geometries acting as a sealant to reduce paravalvular leak. Methods: Polymeric hydrogels were prepared from ABA block copolymer macromers composed of diacrylate terminated by PLA-b-PEG-b-PLA. Hydrogel networks were prepared by swelling these macromers, following the addition of free radical initiators. Hollow tubular constructs were formed via melt-processing in PDMS molds to fit as a “sleeve” around deployed PolyV® nitinol stent (Fig 1A). The sealing efficacy of polymers was examined using a silicone replica of CAVD aortic root with deployed stent + polymer construct (Fig 1B). A rubber stopper was used to fully occlude aortic lumen and restrict flow to paravalvular areas for quantitative analysis. To test sealing against hydrostatic pressure, valve construct was connected to Tygon tubing and water was added at equivalent 10 mmHg increments at 5-minute intervals. Volume from paravalvular flow was measured at each step. Experiments were performed with N = 4 polymeric sleeves. Results: We found significant reduction in paravalvular leakage with polymer sleeves compared to no polymer at all pressures tested. Figure 1C shows the mean ± standard deviation volume of water leaked over 5 minutes of corresponding hydrostatic pressure. No leakage was detected up to 60mmHg for all polymer sleeves tested. At approximately 85-90 mmHg, the rubber stopper failed, however the polymer sleeve remained intact. Conclusions: Polymeric paving utilized with TAVR is a promising combinative therapy for preventing paravalvular leakage. Our results indicate that potential polymeric biomaterials are capable of conforming to non-physiologic aortic valve morphologies, filling and sealing paravalvular gaps, while withstanding physiologic trans-aortic pressures. With further translation, polymer paving can be useful in improving TAVR outcomes.

Abstract 820: Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model

Abstract The ability to treat tumors with high efficacy in a local microenvironment, while mitigating the side effects of systemic toxicity is an area of active investigation. Towards this goal, designing a minimally-invasive local therapeutic modality, with a controlled, pulsatile drug release mechanism is an attractive proposition. In this study, a near-infrared (NIR) photo-activatable microparticle was developed for localized, pulsatile delivery of encapsulated anticancer drugs into the tumor with simultaneous thermal ablation, with controlled ON-OFF thermal cycles using NIR laser irradiation. The microparticles were fabricated using a poly(caprolactone) (PCL) matrix, containing 2D molybdenum disulfide (MoS2) nanosheets as the NIR-responsive photothermal agent, and doxorubicin or violacein, as hydrophilic and hydrophobic model anticancer drugs, respectively. Cubic microparticles of 200 µm size were fabricated by casting a polymer-MoS2-drug film on PDMS mold with loading efficiency of 2 μg MoS2 per particle, and 0.2-8 μg of drug per particle. A cytotoxicity assay was performed to test the efficacy of the loaded microparticles in reducing the viability of 4T1 murine-derived cell culture, using the ON-OFF laser switch mechanism. In order to select a suitable laser power and duration of treatment for in vivo studies, a Machine Learning algorithm based on a Random Forest classifier was trained, to arrive at the optimal treatment conditions: 0.4-0.5 W/cm2 of laser power at 808 nm, for 3 cumulative minutes of laser irradiation, to reach the target temperature of 50 °C, which activates PCL melting and subsequent drug release. The effect of pulsatile treatment was studied in vivo in a murine-derived 4T1 subcutaneous mouse model of breast cancer, using this photo-activatable ON-OFF switch mechanism, for up to 3 cycles of laser irradiation. As control groups, tumor only (no treatment), laser only (no drug or microparticle), drug only (no laser or microparticle), microparticles only (no drug or laser), and microparticles with laser (no drug) were studied. The cohorts receiving the photo-activated 3-cyclic treatment for both drugs showed increased median survival up to 40 days post tumor induction, compared to a median survival of 16 days for the control groups. Although one laser cycle was enough to trigger drug release, there was a significant shrinkage in the tumor volume noticed with 3 cycles, with eventual scarring and shedding of the tissue with no evidence of residual tumor at the primary site. While this cyclic drug release modality is very effective at treating the primary site, subsequent histopathology revealed that the aggressive tumor in some animals had metastasized to the liver and other organs. More work is ongoing to design better targeted approaches to deliver the drug-loaded microparticles to the site of metastatic tumors, to increase the survival prospects of this disease. Citation Format: Maria Kanelli, Neelkanth M. Bardhan, Morteza Sarmadi, Shahad Alsaiari, William Rothwell, Apurva Pardeshi, Angela M. Belcher, Ana Jaklenec, Robert S. Langer. Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 820.

초정밀 레이저를 이용한 연꽃잎 표면 자연 모사 연구

In a pilot natural super-hydrophobic surfaces study, a super-hydrophobic surface was made by coating, etching, laser ablation, chemical vapor deposition and lithography. In this study, cone-shaped periodic micro and nano-structures were constructed on a silica surface with femtosecond and picosecond laser, and the period of micro-structures between cone shape patterns was increased with 10 μm intervals. The contact angle and image of the super-hydrophobic surface were analysed and the cone (Aspect-ratio 1.27) shape model with micro-protrusion structure similar to the surface of the lotus leaf was made to measure the contact angle. To analyse the differences in the contact angles between the cone shapes and heights of the micro-protrusion, different samples with cone (Aspect-ratio 1.27), sphere (Aspect-ratio 1.00) shapes were made through laser micro-machining technology. To mimick the natural lotus leaves, the optimum condition was a cone shape. Samples of PDMS with different shapes and mixed micro/nano-structures were fabricated with a PDMS mold insert. The largest contact angle was measured at 170.42° which is similar to the contact angle of the lotus leaf. This mold insert could be used repeatedly. The molding process is advantageous for large areas and mass production.

Modulating neuronal cell migration under curved confinements

During brain development in the cortical plate, neuronal cells exhibit distinct tangential and radial migration strategies. In case of complications, e.g., inadequate or disordered migration, developmental disorders such as lissencephaly, subcortical band heterotopia, and polymicrogyria can occur. Under healthy conditions, excitatory pyramidal neurons migrate radially from the ventricular zone into the cortical plate before switching to tangential routes. Radial migration has been extensively studied, but the mechanical cues of the tangential phase have been less scrutinized. Furthermore, additional cortical folding may superimpose critical mechanical cues to the tangential migration process. Using multi-curvature micropatterns, we studied synergistic physical and chemical cues that act upon neurons during curved tangential migration. First, PC12 cells (rat, P8) were cultured on polystyrene Petri dishes coated with poly-L-lysine (PLL) for control and with 3% (w/v) agarose micro curvatures on PLL, with media containing DMEM (97%), FBS (1%), HS (1%), and PenStrep (1%). These curvatures consisted of multiple concentric circles of increasing radii, with agarose barriers between each circle, and were created by stamping agarose with a 10:1 PDMS mold. Cell motility was imaged for 24 h in vitro (Dino-Lite microscope, 15 min interval) and tracked in FIJI ImageJ Manual Tracking software. Preliminary results indicate that neurons in the multi-curvatures migrated on average 45 times faster than under control conditions. These initial findings may be a starting point for better understanding physical cues during tangential migration strategies in the developing brain.

Elasto-Inertial Particle Focusing in Microchannel with T-Shaped Cross-Section

Recently, particle manipulation in non-Newtonian fluids has attracted increasing attention because of a good particle focusing toward the mid-plane of a channel. In this research, we proposed a simple and robust fabrication method to make a microchannel with various T-shaped cross-sections for particle focusing and separation in a viscoelastic solution. SU-8-based soft lithography was used to form three different types of microchannels with T-shaped cross-sections, which enabled self-alignment and plasma bonding between two PDMS molds. The effects of the flow rate and geometric shape of the cross-sections on particle focusing were evaluated in straight microchannels with T-shaped cross-sections. Moreover, by taking images from the top and side part of the channels, it was possible to confirm the position of the particles three-dimensionally. The effects of the corner angle of the channel and the aspect ratio of the height to width of the T shape on the elasto-inertial focusing phenomenon were evaluated and compared with each other using numerical simulation. Simulation results for the particle focusing agreed well with the experimental results both in qualitatively and quantitatively. Furthermore, the numerical study showed a potential implication for particle separation depending on its size when the aspect ratio of the T-shaped microchannel and the flow rate were appropriately leveraged.

점탄성 유체 내 미세입자 분리용 고종횡비 미세유체 디바이스 제작

In this study, we propose a novel and simple fabrication method of the microfluidic device, with high-aspect-ratio (HAR) microchannel for microparticle separation under viscoelastic fluid flow. To fabricate the HAR ( 10) microfluidic device comprised of the Si channel and PDMS mold, basic MEMS processes such as photolithography, reactive ion etching and anisotropic wet etching of Si wafer were used, and then plasma bonding with mechanical alignment between the Si channel and PDMS mold was conducted. The width of the microchannels was determined by the difference between the Si channel width and the master width for the PDMS mold. On the other hand, the heights of the Si channel and PDMS mold could be controlled by the KOH etching time and spin-coating speed of SU-8, respectively. The HAR microfluidic device whose microchannel had 10 μm width and 100 μm height was successfully fabricated, and used to separate microparticles without other external forces. The effect on the particle focusing position and focusing width under viscoelastic fluid was investigated, depending on the flow rate and the microparticle size. It is expected that precise manipulation as well as high-throughput separation of microparticles, can be achieved using the microfluidic device with HAR microchannel.

Flexible ionic-gel strain sensor with double network, high conductivity and high frost-resistance using electrohydrodynamic printing method

Ionic-gel sensors have attracted wide attention in the fields of flexible electronic skin and wearable devices. However, the weak mechanical properties of ionic gels have hindered their large-scale applications. In this work, the electrohydrodynamic (EHD) printing method was proposed to prepare the ionic-gel film in the PDMS mold, and then the ionic-gel film with the double-network (DN) structure was formed under the induction of ultraviolet (UV) light, which greatly improved the electrical conductivity of the ionic-gel film. The CS-(AA-HEMA)-DN ionic-gel film was prepared via interpenetrating the acrylic acid and 2-hydroxyethyl methacrylate (AA-HEMA) network into chitosan (CS) network in 1-butyl-3-methylimidazolium chloride ([BMIM]Cl). The tensile strength of the CS-(AA-HEMA)-DN ionic-gel film is 0.28 MPa under 335 % strain. The electrical conductivity is 1.231 × 10-3 S/cm, and the response time is 81 ms. Therefore, the CS-(AA-HEMA)-DN ionic-gel film has excellent mechanical properties, high conductivity, and fast response time at room temperature. In addition, the CS-(AA-HEMA)-DN ionic-gel film has high frost-resistance and still has good mechanical properties, high conductivity and stability at a low temperature (−60 ℃). The CS-(AA-HEMA)-DN ionic-gel film can be used as a flexible strain sensor for monitoring human motion due to its superior electromechanical properties. Thus, the high-performance flexible ionic-gel strain sensor has broad application prospects in the field of flexible electronics.

Production of cultured meat from pig muscle stem cells

Cultured meat is meat for consumption produced in a more sustainable way. It involves cell harvesting and expansion, differentiation into myotubes, construction into muscle fibres and meat structuring. We isolated 5.3 × 104 porcine muscle stem cells from 1 g of neonatal pig muscle tissue. According to calculations, we need to expand muscle stem cells 106-107 times to produce 100 g or 1 kg of cultured meat. However, the cells gradually lost the ability to express stemness and mature muscle cell markers (PAX7, MyHC). To tackle this critical issue and maintain cell function during cell expansion, we found that long-term culture with (100 μM) l-Ascorbic acid 2-phosphate (Asc-2P) accelerated cell proliferation while preserving the muscle cell differentiation. We further optimized a scalable PDMS mold. Porcine muscle stem cells formed structurally-organized myotubes similar to muscle fibres in the mold. Asc-2P enhanced porcine muscle cells grown as 3D tissue networks that can produce a relatively large 3D tissue networks as cultured meat building blocks, which showed improved texture and amino acid content. These results established a realistic workflow for the production of cultured meat that mimics the pork meat structurally and is potentially scalable for industry.

Microcontact surface imprinting of affinity peptide for electrochemical impedimetric detection of neutrophil gelatinase-associated lipocalin

In this study, a specific binding peptide (BP1)-imprinted film comprising crosslinked poly(acrylamide-co-diallyamine-co-N,N′-methylenebisacrylamide) matrix was photochemically fabricated on a gold-coated quartz crystal electrode for detecting neutrophil gelatinase-associated lipocalin (NGAL), a promising biomarker of inflammatory bowel disease. Microcontact surface imprinting was performed using a BP1 template-adsorbed PDMS mold with a concave hemispherical array to form patterned films. The surface morphologies of the molecularly imprinted polymer (MIP) films were characterized using scanning electron microscopy (SEM), and the limit of detection (LOD, 0.07 μg/mL) and limit of quantification (LOQ, 0.24 μg/mL), including sensitivity and reproducibility, were investigated using electrochemical impedance spectroscopy (EIS). Moreover, the sensing properties of (NGAL-BP1)-imprinted MIP (“I-MIP”)-assisted biosensors for detecting NGAL protein were investigated using differential pulse voltammetry (DPV) and EIS. Normalized current peak (IN) and impedance (RN) values linearly increased with NGAL ranging from 1 to 300 ng/mL. Moreover, the selectivity coefficient (k* ) of NGAL proteins on the BP1-imprinted film was 3.5–5.8 against bovine serum albumin for the binding process in the entire low-concentration range owing to a high affinity between the imprinted BP1 peptide and target NGAL protein. Remarkable impedance difference was registered with respect to different stages of the Crohn’s disease with the biosensors at the adsorption of NGAL proteins using samples from real patients. Moreover, the NGAL concentration measured using the developed (I-MIP)-assisted biosensors was comparable with that estimated using the commercially available enzyme-linked immunosorbent assay (ELISA). Therefore, peptide-imprinted biosensors based on electrochemical impedance sensing platforms are potentially promising for detecting macromolecular proteins.

The Production of Fat-Containing Cultured Meat by Stacking Aligned Muscle Layers and Adipose Layers Formed From Gelatin-Soymilk Scaffold.

Tissue engineered cultured meat has been proposed as an emerging innovative process for meat production to overcome the severe consequences of livestock farming, climate change, and an increasing global population. However, currently, cultured meat lacks organized tissue structure, possesses insufficient fat content, and incurs high production costs, which are the major ongoing challenges. In this study, a developed scaffold was synthesized using gelatin and soymilk to create a friendly environment for myogenesis and adipogenesis in C2C12 and 3T3-L1 cells, respectively. The fat containing cultured meat was fabricated with an aligned muscle-like layer and adipose-like layer by stacking these layers alternately. The muscle-like layer expressing myosin and the adipose-like layer abundant in fat were sandwiched to form fat containing muscle tissue. The cytotoxicity and cell survival rate were evaluated using the WST-1 assay and live/dead staining. Myogenesis was confirmed by the expression of myogenin and myosin. The myotubes, myofibrils, and sarcomeres were observed under an inverted microscope, fluorescence microscope, and scanning electron microscope. Adipogenesis was evaluated by protein expression of the peroxisome proliferator-activated receptor γ, and oil droplet accumulation was determined by fluorescence microscopy with Nile Red stain. Extracellular matrix secretion was examined by safranin-O staining. In this study, the cultured meat was prepared with muscle-like texture with the addition of pre-adipocyte, where the multilayered muscle-like tissues with fat content would produce juicy cultured meat.

PolyJet-Based 3D Printing against Micromolds to Produce Channel Structures for Microchip Electrophoresis.

In this work, we demonstrate the ability to use micromolds along with a stacked three-dimensional (3D) printing process on a commercially available PolyJet printer to fabricate microchip electrophoresis devices that have a T-intersection, with channel cross sections as small as 48 × 12 μm2 being possible. The fabrication process involves embedding removable materials or molds during the printing process, with various molds being possible (wires, brass molds, PDMS molds, or sacrificial materials). When the molds are delaminated/removed, recessed features complementary to the molds are left in the 3D prints. A thermal lab press is used to bond the microchannel layer that also contains printed reservoirs against another solid 3D-printed part to completely seal the microchannels. The devices exhibited cathodic electroosmotic flow (EOF), and mixtures of fluorescein isothiocyanate isomer I (FITC)-labeled amino acids were successfully separated on these 3D-printed devices using both gated and pinched electrokinetic injections. While this application is focused on microchip electrophoresis, the ability to 3D-print against molds that can subsequently be removed is a general methodology to decrease the channel size for other applications as well as to possibly integrate 3D printing with other production processes.

A Simple Method for Fabricating Ink Chamber of Inkjet Printheads.

The process of fabricating chambers is becoming more important for inkjet printheads. However, there are some problems with the majority of present fabrication methods, such as nozzle structural deformation, blocked chambers, and collapsed chambers. In this paper, we propose a new process for preparing printhead chips by bonding tantalum nitride thin-film heaters and SU-8 chamber film using UV curing optical adhesive. This process simplifies the preparation process of printhead chips and overcomes the limitations of the traditional adhesive bonding process. Firstly, a chamber film was prepared by the molding lithography process based on a PDMS mold. The chamber film was then bonded with the membrane heater by the adhesive bonding process based on film transfer to form a thermal bubble printhead chip. Finally, the chip was integrated with other components to form a thermal inkjet printhead. The results show that the overflow width of bonding interface of 3.10 μm and bonding strength of 3.3 MPa were achieved. In addition, the printhead could stably eject polyvinyl pyrrolidone binder droplets, which are expected to be used for binder-jetting printing of powder such as ceramics, metals, and sand molds. These results might provide new clues to better understand the adhesive bonding process based on film transfer and the new applications of inkjet printheads.

Improved PDMS mold fabrication by direct etch with nanosphere self-assembly mask for Soft UV-NIL subwavelength metasurfaces fabrication

With the increased relevance of metasurface for optical applications, a fabrication method that allows for both large surface and 100 nm range dimensions at a low cost is required for their development. Due to its high throughput and small structuration capabilities, Soft Nanoimprint Lithography is a good canditate as fabrication method for these type of devices. But its application for metasurfaces at visible wavelengths has been hindered by the necessity to use low-viscosity PDMS in order to reach the dimensions required, making the final stamp more fragile and the process more expensive. Here we propose a PDMS mold fabrication method which relies on self-assembly masking of the PDMS followed by direct etching of the mold, decorrelating the minimum dimension attainable from the PDMS viscosity. We characterize a metasurface fabricated using a mold obtained with our method validating its use for nanofabrication of large surface devices.

High-Aspect-Ratio Microfluidic Channel with Parallelogram Cross-Section for Monodisperse Droplet Generation.

Droplet-based microfluidics has been widely used as a potent high-throughput platform due to various advantages, such as a small volume of reagent consumption, massive production of droplets, fast reaction time, and independent control of each droplet. Therefore, droplet microfluidic systems demand the reliable generation of droplets with precise and effective control over their size and distribution, which is critically important for various applications in the fields of chemical analysis, material synthesis, lab-on-a-chip, cell research, diagnostic test, and so on. In this study, we propose a microfluidic device with a high-aspect-ratio (HAR) channel, which has a parallelogram cross-section, for generating monodisperse droplets. The HAR channel was fabricated using simple and cheap MEMS processes, such as photolithography, anisotropic wet etching, and PDMS molding, without expensive equipment. In addition, the parallelogram cross-section channel structure, regarded as a difficult shape to implement in previous fabrication methods, was easily formed by the self-alignment between the silicon channel and the PDMS mold, both of which were created from a single crystal silicon through an anisotropic etching process. We investigated the effects of the cross-sectional shape (parallelogram vs. rectangle) and height-to-width ratio of microfluidic channels on the size and uniformity of generated droplets. Using the developed HAR channel with the parallelogram cross-section, we successfully obtained smaller monodisperse droplets for a wider range of flow rates, compared with a previously reported HAR channel with a rectangular cross-section.

Responsive hydrogel-based microneedle dressing for diabetic wound healing.

Wound healing is a critical challenge in diabetic patients, mainly due to long-term dysglycemia and its related pathological complications. Subcutaneous insulin injection represents a typical clinical solution, while the low controllability of insulin administration commonly leads to a result far from the optimal therapeutic effect. In this work, we developed a glucose-responsive insulin-releasing hydrogel for microneedle dressing fabrication and then investigated its effects on diabetic wound healing. The hydrogel system was composed of biocompatible gelatin methacrylate (GelMa), glucose-responsive monomer 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA) and gluconic insulin (G-insulin), and the Gel-AFPBA-ins hydrogel-based microneedle dressing was developed by replicating PDMS molds. The resultant hydrogel microneedle dressing exhibited adequate mechanical properties, high biocompatibility, glucose-responsive insulin release behavior upon exposure to different glucose solutions, and potent adhesion to the skin compared to hydrogels without microstructures. The microneedle dressing could accelerate the diabetic wound healing process with decreased inflammatory reaction, enhanced collagen deposition on the regenerated tissue sites, and improved blood glucose control in animals. Therefore, the glucose-responsive insulin-releasing hydrogel microneedle dressing is effective in diabetic wound management and has potential for treatment of other chronic skin injuries.