Micromolding Process Research Articles

Polypropylene-Based Polymer Locking Ligation System Manufacturing by the Ultrasonic Micromolding Process.

In recent years, there has been a growing demand for biocompatible medical devices on the microscale. However, the manufacturing of certain microfeatures has posed a significant challenge. To address this limitation, a new process called ultrasonic injection molding or ultrasonic molding (USM) has emerged as a potential solution. In this study, we focused on the production of a specific microdevice known as Hem-O-Lok, which is designed for ligation and tissue repair during laparoscopic surgery. Utilizing USM technology, we successfully manufactured the microdevice using a nonabsorbable biopolymer that offers the necessary flexibility for easy handling and use. To ensure high-quality microdevices, we extensively investigated various processing parameters such as vibration amplitude, temperature, and injection velocity. Through careful experimentation, we determined that the microdevice achieved optimal quality when manufactured under conditions of maximum vibrational amplitude and temperatures of 50 and 60 °C. This conclusion was supported by measurements of critical microfeatures. Additionally, our materials characterization efforts revealed the presence of a carbonyl (C=O) group resulting from the thermo-oxidation of air in the plasticizing chamber. This finding contributes to the enhanced thermal stability of the microdevices within a temperature range of 429-437 °C.

A comparison of dissolving microneedles and transdermal film with solid microneedles for iloperidone in vivo: a proof of concept.

Iloperidone (ILO) is a poorly soluble and bioavailable WHO-approved schizophrenia drug. Microneedles are a revolutionary delivery technology that overcomes many of the issues associated with traditional drug administration. The current research aimed to compare the antipsychotic activity and pharmacokinetics of ILO-loaded dissolving microneedles (DMNs) and transdermal film with a solid microneedle (STF). The DMNs were fabricated using the micromolding process, while the transdermal film was created using the solvent casting approach. Furthermore, an in vivo pharmacokinetic, pharmacodynamic, and skin irritation study was performed on Wistar rats. Studies were compared with transdermal film (TF) on untreated skin as a passive control. STF and DMNs had considerably greater AUC and Cmax (p ≤ 0.001) than transdermal film. In pharmacodynamic tests, STF and DMNs demonstrated significant (p ≤ 0.001) forelimb retraction time (FRT) and hindlimb retraction time (HRT) delay responses as compared to control and TF. In the skin irritation test, no adverse effects such as erythema or edema were observed at the end of the 48h. Thus, antipsychotic activity (paw test) and pharmacokinetics studies revealed sustained action of DMN and STF. This research revealed that improved efficacy of DMN and STF for antipsychotic drug delivery may be an alternative to the existing dosage form.

Strategy for the fabrication of perovskite-based green micro LED for ultra high-resolution displays by micro-molding process and surface passivation

Perovskite is an emerging material for light-emitting diode (LED) applications, and the external quantum efficiency (EQE) of perovskite LEDs (PeLEDs) has rapidly improved compared to state-of-the-art organic and quantum-dot LEDs. In addition, mini/micro LEDs have attracted significant attention as next-generation displays owing to their desirable characteristics such as low power consumption, high contrast ratio, high brightness, fast response speed, and high efficiency. In this study, we successfully develop a high-resolution large-area soft lithography method for the micro-patterning of a perovskite emissive layer. This approach is based on micro- and capillary-molding processes, and the highest achievable pattern resolution is 5 μm. In addition, to further improve the efficiency and stability of the micro PeLEDs, various polymers with different functional groups are applied to passivate the perovskite surface. Consequently, the CsPbBr3–polyacrylonitrile (PAN) micro PeLEDs demonstrate the optimum performance and high stability, with the maximum EQE of 12.8 %, maximum luminance of 10737 cd m−2, and half-life of 993 s with 1270 pixels per inch (ppi). Our work demonstrates the feasibility of micro-patterned perovskites as well as the potential of perovskites for use in ultra high-resolution displays (UHDs).

Development of dissolvable microneedle patches by CNC machining and micromolding for drug delivery

This study reports the fabrication of microneedles using computer numerical control (CNC) machining and micromolding for replicating dissolvable microneedles (DMNs) for drug delivery. Despite the ease of use and simple manufacturing by CNC, this method has not been extensively studied for the fabrication of microneedles. The master molds were fabricated using CNC machining; subsequently, DMNs embedded with fluorescent dye as a drug model were prepared using a hyaluronic acid (HA) and polyvinylpyrrolidone (PVP) solution in a rapid and comparatively simple micromolding process. The microneedles were evaluated for mechanical strength and penetration efficiency. The drug diffusion from DMNs was elucidated through confocal laser scanning microscopy (CLSM) imaging. The results show that fabricated DMNs are mechanically strong enough to penetrate the skin dermis layer and deliver their therapeutic cargo. In conclusion, CNC machining can provide rapid and low-cost fabrication of master molds, facilitating DMNs production for transdermal drug delivery.

Moldable and transferrable conductive nanocomposites for epidermal electronics

Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring, human–machine interface, and the Internet of things. Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices. However, realizing conductive nanocomposites with high conductivity, electromechanical stability, and low modulus over a large area at sub-100 μm resolution remains challenging. Here, we report a moldable, transferrable, high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate). The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual components. We patterned the nanocomposite via a simple, low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft, skin-interfaced electrophysiological sensors. Electrophysiological signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel electrodes. The nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.

Controllable and Scalable Fabrication of Superhydrophobic Hierarchical Structures for Water Energy Harvesting

We report a controllable and scalable fabrication approach for the superhydrophobic hierarchical structures and demonstrate the excellent ability to harvest water energy when applied to water-solid contact triboelectric nanogenerator (TENG). A strategy combined with multiple photolithography and micromolding process was developed to accurately regulate the diameters and the center distances of the two-level micropillars. A variety of hierarchical structures were successfully fabricated and presented the advantages of structure control, large scale, high accuracy, and high consistency. The hydrophobic property characterizations were conducted, and the results indicated that the hierarchical structures showed a larger contact angle than the single-level structures and achieved superhydrophobicity. Then the hierarchical structures were applied to water-TENGs with flowing water continuously dripping on, and the effect of the structure parameter on the triboelectric output was analyzed. The hierarchical structures exhibited a superior ability to harvest water energy than the flat film and the single-level structures due to the enhanced friction area and superhydrophobic property. At a flowing velocity of 8 mL/s, the hierarchical structure generated the output voltage of approximately 34 V and the short-circuit current of around 5 μA. The water-TENG device exhibited a power density peak of 7.56 μW/cm2 with a resistive load of 16.6 MΩ at a flowing velocity of 10 mL/s. These findings shed light on the potential applications of the hierarchical structures-based water-TENGs to water energy harvesting and self-powered sensor devices.

Highly antifouling porous EVAL/F127 blend membranes with hierarchical surface structures

Membrane fouling is widely acknowledged as the major hindrance to the efficient separation of oil-water emulsions. Superhydrophilic EVAL/F127 porous membranes with micron-submicron hierarchical structure were prepared via micro-molding assisted immersion precipitation (PSμm process). The micron-scale concave-convex structure was constructed by the micro-molding process with 1000 mesh sandpaper, and then the sub-micron structure of the surface was modulated by F127. With the combination of optimized hierarchical structure and F127 hydrophilic modifier, EVAL/F127 porous membrane is superhydrophilic (water contact angle less than 10°) and strongly anti-fouling. ATR-FTIR, SEM, AFM, water contact angle (WCA), pure water flux, porosity and equilibrium water content were used to characterize the textural and properties of EVAL porous membranes. The separation performance and antifouling properties of the membranes were evaluated using oil-in-water emulsions as fouling agents. When the F127 content was 10%, the EVAL/F127 blended porous membrane not only performed well in retention performance (95.3% retention), but also had high flux recovery (91.6%) after hydrodynamic cleaning. Thus, the combined strategy based on hierarchical structure and hydrophilic modification provides a facile solution for the preparation of antifouling membranes.

Microfluidic Thermal Flowmeters for Drug Injection Monitoring

This paper presents a microfluidic thermal flowmeter for monitoring injection pumps, which is essential to ensure proper patient treatment and reduce medication errors that can lead to severe injury or death. The standard gravimetric method for flow-rate monitoring requires a great deal of preparation and laboratory equipment and is impractical in clinics. Therefore, an alternative to the standard method suitable for remote, small-scale, and frequent infusion-pump monitoring is in great demand. Here, we propose a miniaturized thermal flowmeter consisting of a silicon substrate, a platinum heater layer on a silicon dioxide thin-membrane, and a polymer microchannel to provide accurate flow-rate measurement. The present thermal flowmeter is fabricated by the micromachining and micromolding process and exhibits sensitivity, linearity, and uncertainty of 0.722 mW/(g/h), 98.7%, and (2.36 ± 0.80)%, respectively, in the flow-rate range of 0.5–2.5 g/h when the flowmeter is operated in the constant temperature mode with the channel width of 0.5 mm. The measurement range of flow rate can be easily adjusted by changing the cross-sectional microchannel dimension. The present miniaturized thermal flowmeter shows a high potential for infusion-pump calibration in clinical settings.

Tensile, rheological and morphological characterizations of multi-walled carbon nanotube/polypropylene composites prepared by microinjection and compression molding

Abstract Polypropylene (PP) reinforced with 2 and 4 wt% of multi-walled carbon nanotubes (MWNT) were melt-blended in twin screw extruder and then molded by compression or micromolding process. The impact of injection speed on the surface morphology, rheological and tensile characteristics was investigated by using a scanning electron microscope, parallel plate rheometry, and tensiometry. Results showed that the tensile properties of micro-molded specimens were remarkably higher than those of the compression molded sheets. Compared to compression molded sheets, micromolded specimens demonstrated up to 40 and 244% higher tensile stiffness and yield strength, respectively, most likely due to the alignment of polymer chain segments in the flow direction induced during the micromolding process. It was observed that the fast filling speed caused a drop in the tensile properties of the nanocomposites and polymer. Rheological examination revealed that the presence of a rheological percolation network in the nanocomposites produced by micromolding and the fast injection speed was beneficial for establishing the percolated network. Morphological examination revealed that the size of nanotube agglomerations that appeared in micromolded specimens was up to five times smaller than in compression molded sheets and the agglomeration size decreased with the increase of the injection speed.

A novel method for fabrication of coated microneedles with homogeneous and controllable drug dosage for transdermal drug delivery.

Over the years, scientists have been focused on the development of microneedle coating process to coat a broad range of therapeutic agents onto the surface of the solid microneedles for effective drug delivery. The precise dose control, content uniformity as well as large-scale production of coated microneedles are still the core issues that have been the interest of researchers in this topic. To this end, a repeatable method that involved a micro-molding process was demonstrated for mass fabrication of coated microneedles with homogeneous and controllable drug loading under mild conditions. In this system, the dissolvable drug carriers with precise dosage were first mounted onto the solid microneedles and then exposed to the high moisture condition to finally obtain the coated microneedle with uniform and precise drug loading. Using the microneedle molds with the volume of 4.71 nL, 8.24 nL, 10.47 nL, and 12.56 nL per cavity, the drug loadings were precisely controlled at 4.8 ng, 6.4 ng, 9.3 ng, and 13.5 ng per needle, with the standard deviation of 0.09, 0.01, 0.07, and 0.53%, respectively. Mechanical property tests showed that the coated microneedles are strong enough for reliable skin insertion, and with in vivo trials in diabetic mice, we further confirmed the similar hypoglycaemic effect of insulin-coated microneedles to subcutaneous injection. Taken together, the micro-molding-based fabrication process has practical merits in the mass production of coated microneedles with homogeneous and controllable drug loading, facilitating the clinical translation of the microneedle technique.

Rapid prototyping and customizable microneedle design: Ultra-sharp microneedle fabrication using two-photon polymerization and low-cost micromolding techniques

In recent years, interest in microneedle devices for drug and vaccine delivery and point-of-care diagnostics has grown due to low cost, convenience and minimal invasiveness. A cluster of miniature needles on a small patch could enhance the quality of human health care, revolutionizing test and drug and vaccine delivery systems. However, current fabrication methods are not viable for cost-effective large-scale manufacture. This study reports fabrication of ultra-sharp microneedles with microfluidic channels using two-photon polymerization (2PP) which enables flexible designs with resolution down to 100 nm. The technique is ideally suited to prototyping and the fabrication of master molds from which elastomeric negative-molds have been used in a rapid micromolding technique to make batches of ultra-sharp microneedles. This micromolding process has mass manufacturing potential.

In situ synchrotron small angle X-ray scattering investigation of structural formation of polyethylene upon micro-injection molding

A customized micro-injection molding apparatus with a pair of diamond windows in the filling cavity was specifically designed to simulate the extreme processing conditions inherent in the practical micro-molding process. This setup combined with synchrotron radiation allows real-time investigation of multi-scale structural development during the manufacturing process, which enables evaluation of flow-induced crystallization features for a range of polymeric materials. In this study, the structural evolution of high density polyethylene at the nanoscale was investigated by in situ synchrotron small angle X-ray scattering technique under injection molding. The respective structural parameters of kebab lamellae (including the long period, and the average thickness of crystalline lamellae and amorphous phase) and shish formation (such as the radius of gyration, length, and misorientation of the shish) were extensively analyzed from the resulting data. The growth of kebab crystals was found to exhibit a two-step behavior: melting of thin crystallites followed by a recrystallization process occur at the onset of molding whereas an annealing-induced perfectioning of the lamellae is activated at a later stage. In spite of the initial decrease of the shish length and radius, there is an overall increase in the length and misorientation of the shish structure at later times, which can be attributed to a crystallization of partially oriented chains onto the longitudinal surface of the existing shish. The results acquired by the unique combination of this apparatus and synchrotron radiation can provide an effective means to predict the structural formation and modulate the morphology of final products in practical micro-injection molding process of polymers.

Self-Adhesive Microneedles with Interlocking Features for Sustained Ocular Drug Delivery.

The interests in sustained ocular drug delivery have grown rapidly in recent years, with hope to replace repeated intravitreal injections. Microneedles (MNs), which are minimally invasive, have been shown to be a feasible vehicle for sustained drug delivery. However, securing an MN patch in the eye remains challenging. In this study, a new design of hydrogel MNs with interlocking features to achieve self-adhesion is proposed. Upon swelling, the swollen interlocking features help secure the MNs in place. A new molding process is developed to fabricate MNs with interlocking features that can cause issues when demolding using the regular micromolding process. MNs with two different interlocking feature designs are used in this study and are made with polyvinyl alcohol. MNs with the interlocking features show an 80% increase in adhesion strength and a small amount of increase in penetration force, in comparison to MNs without any feature. The experiments are performed using both a sclera-mimicking phantom and ex vivo eyes harvested from rabbits and are shown to have comparable results. This study demonstrates the feasibility of incorporating interlocking features to MNs to achieve self-adhesion that can enable sustained drug delivery via MNs.

Effect of the Thermal History on the Crystallinity of Poly (L-lactic Acid) During the Micromolding Process.

The micromolding process using biocompatible thermoplastic polymers is highly attractive as a fabrication process of microdevices in biomedical applications. In this study, we investigated the effect of the thermal history in the micromolding process on the crystallinity of semi-crystalline polymers, such as poly (L-lactic acid) (PLLA), during their crystallization from the amorphous and molten states. In particular, the thermal history in the micromolding process using poly(dimethylsiloxane) replica mold embedded with a thermocouple was recorded. The crystallinity of PLLA constructs fabricated using the micromolding process was measured via wide-angle X-ray scattering, and crystallization kinetics was analyzed based on the Kolmogorov–Johnson–Mehl–Avrami equation. A crystallization rate of k = 0.061 min−n was obtained in the micromolding process of PLLA crystallization from the amorphous state, accompanied by the quenching operation, forming a large number of crystal nuclei. Finally, the fabrication of PLLA microneedles was performed using micromolding processes with different thermal histories. The information about the thermal history during the micromolding process is significant in the development of polymer microdevices to achieve better material properties.

Fabrication of Tip-Hollow and Tip-Dissolvable Microneedle Arrays for Transdermal Drug Delivery.

We developed a modified micromolding method for the mass production of a novel tip-hollow microneedle array (MA). The tip-hollow MA was fabricated by tuning of the vacuum degree at -80 kPa for 60 s during the micromolding process. Subsequently, a tip-dissolvable MA encapsulated with drugs in the microcraters was fabricated from tip-hollow MA using repeated dipping and the freeze-drying process. Both the tip-hollow and tip-dissolvable MAs could easily penetrate in the rabbit skin without breakage, while the tip-hollow MA can just create a shallow loop hole in the skin. The drug-loaded tip-dissolvable MA can rapidly dissolve, releasing and diffusing the drug in the skin. The tip-dissolvable MA exhibited the best drug permeation ability in that the corresponding flux through the punctured skin using tip-dissolvable MA loaded with Rhodamine B is about 1.7- and 5.8-fold of that through the punctured skin using solid MA and the intact skin, respectively. The tip-dissolvable MA loaded with 5 IU insulin was fabricated to in vivo treat the type 1 diabetic SD rats. The tip-dissolvable MA had a good hypoglycemic effect and exhibited longer normoglycemic period in comparison with subcutaneous injection (5 IU). Therefore, our tip-dissolve MA is a promising medical device for transdermal drug delivery.

Preparation and characterization of dissolving hyaluronic acid composite microneedles loaded micelles for delivery of curcumin.

In order to improve the bioavailability of curcumin (Cur) and patient compliance, a type of novel hyaluronic acid (HA) composite microneedles containing Cur-loaded micelles was designed in this paper. On the one hand, the microneedles matrix solution was prepared by screening the optimal concentration of HA and the better proportion of HA to sodium carboxymethyl starch (CMS-Na). On the other hand, the amphiphilic polymer, named as Quercetin-Dithiodipropionic Acid-Oligomeric Hyaluronic Acid (Que-DA-oHA), was synthesized and characterized using 1H-NMR. Subsequently, the dialysis method was used to prepare Cur-loaded Que-DA-oHA micelles with an average size of 172.6 ± 11.4nm and zeta potential of - 33.71 ± 0.45mV. A micromolding process was used to prepare the micelle-loaded HA composite microneedles. It had been found that when the concentration of HA was 200mg/mL and the mass ratio of HA to CMS-Na was 2:1, the prepared HA composite microneedles had good mechanical strength. In-skin dissolution kinetics showed that the micelle-loaded HA composite microneedles could dissolve quickly in the skin. In vitro permeation study indicated that the microneedles delivered 74.7% of their drug load over 6h, which exhibited remarkable drug permeation properties in a short time. Here, we creatively combined micellar technology with microneedle technology to rapidly deliver Cur transdermally for diseases treatment such as melanoma. Graphical abstract.

Two-level submicron high porosity membranes (2LHPM) for the capture and release of white blood cells (WBCs).

A method modifying a vacuum-assisted UV micro-molding (VAUM) process is proposed for the fabrication of polymer two-level submicron high porosity membranes (2LHPM). The modified process allows for the fabrication of robust, large-area membranes over 5 × 5 cm2 with a hierarchical architecture made from a 200 nm-thick layer having submicron level pores (as small as 500 nm) supported by a 20 μm-thick layer forming a microporous structure with 10-15 μm diameter pores. The fabricated freestanding membranes are flexible and mechanically robust enough for post manipulation and filtration of cell samples. Very high white blood cell (WBC) capture efficiencies (≈97%) from healthy blood samples after red blood cell (RBC) lysis are demonstrated using a 3D-printed filter cartridge incorporated within these 2LHPM. A high release efficiency of ≈95% is also proved using the same setup. Finally, on-filter multistep immunostaining of captured cells is also shown.

3D-Printed Pneumatic Microfluidic Mixer for Colorimetric Detection of Listeria monocytogenes

Abstract. 3D printing can significantly improve the current fabrication techniques for microfluidic devices due to its ability to create truly 3D structures in a single step. In this study, an active pneumatic microfluidic mixer was designed and fabricated using an extrusion-based 3D printer and used for rapid detection of . The printed material of the mixer is flexible, semi-transparent, and inexpensive. The fabrication time is significantly shorter than the traditional micromolding process. The printed mixer consists of two pneumatic air chambers and one mixing chamber designed for a fluidic sample size of 100 µL. The length, width, and height of the mixer chip are 13, 12.7, and 9 mm, respectively. The performance of the mixer was tested for different actuation frequencies and pneumatic pressures. The completed 3D-printed mixer was successfully applied to the colorimetric detection of for a concentration range from 102 to 108 cfu mL-1 using an enzyme-linked immunosorbent assay. The experimental results showed that the microfluidic mixer could enhance the mixing efficiency of the fluidic sample through pneumatically actuated diaphragms. In addition, the mixer could accelerate the color development caused by target , and the observed color changes could be discriminated within 5 min by naked eye. The present work will contribute to the development and optimization of a prototype for rapid detection of in food samples. It provides an effective technical approach to realize the fabrication of low-cost microfluidic chips for efficient reagent mixing in microscale biochemical detection systems. Keywords: 3D printing, Listeria monocytogenes, Microfluidic mixer, Rapid detection.

Preparation of Colorful, Infrared-Reflective, and Superhydrophobic Polymer Films with Obvious Resistance to Dust Deposition.

In recent years, polymer films containing deep color and near-infrared (NIR)-reflective pigments have received much attention for their potential applications in energy-saving fields. However, in practical environments, dust present in the air is easily adsorbed and adheres to the surface of these films, thus gradually reducing their NIR reflectance. In this work, black or deep-red infrared-reflective pigments were firstly mixed with melted low-density polyethylene (LDPE) and then the resulting composite was thermally pressed on to a metal template possessing micro- and nanostructure surface roughness. After being cooled to a suitable temperature, the LDPE composite film was peeled from the template. Ultraviolet-visible-near-infrared spectroscopy and an indoor infrared lamp irradiation test both confirmed that the prepared films exhibit high NIR reflectance and high heat reflectance. Moreover, due to the stretching-controlled micromolding process, the films all exhibited a superhydrophobic (SH) property. After incubation in outdoor conditions for 1 month, the NIR reflectance of the SH films remained almost consistent; however, the films that did not possess SH property showed a marked decrease in their ability to reflect NIR radiation. By a combination of scanning electron microscopy imaging, we conclude that our films are able to resist dust deposition and thus avoid deterioration of their infrared-reflective properties. We believe that these colorful, infrared-reflective, SH, and cost-effective films have potential application for reducing energy consumption where minimal solar irradiation is required.

Characterizing Ultrasonic Micro-Molding Process of Polyetheretherketone (PEEK)

Abstract Ultrasonic micro-molding technology can dispense, melt and inject as small an amount of polymer as is required for one cycle, an advantage which makes the process highly desirable for low-volume and customized production of micro parts made from sensitive and very expensive polymers, especially in the medical sector. In this study, the feasibility of processing the polyetheretherketone (PEEK) polymer was investigated. The experiments conducted determined the parameters of a process that would allow parts with specific mechanical properties to be produced and verified as not degraded. The development of the process used three amplitude values as well as varying plunger velocity and vibration times. The three amplitude values and four speed values were tested to determine appropriate parameters for the ultrasonic process. Completely filled samples without any visual signs of degradation were analysed using FTIR-ATR, crystallinity percentage and tensile strength tests. Results show that the amplitude parameter is an important factor in the ultrasonic process and the higher its value is, the better the mechanical properties of complete parts are. Moreover, the tensile strength value of the specimens fabricated by ultrasonic micro-molding is comparable to that of conventional injection molding technology.