Micromolding Processes Research Articles

Development of hyaluronic acid-silica composites via in situ precipitation for improved penetration efficiency in fast-dissolving microneedle systems

Fast-dissolving microneedles (DMNs) hold significant promise for transdermal drug delivery, offering improved patient compliance, biocompatibility, and functional adaptability for various therapeutic purposes. However, the mechanical strength of the biodegradable polymers used in DMNs often proves insufficient for effective penetration into human skin, especially under high humidity conditions. While many composite strategies have been developed to reinforce polymer-based DMNs, simple mixing of the reinforcements with polymers often results in ineffective penetration due to inhomogeneous dispersion of the reinforcements and the formation of undesired micropores. In response to this challenge, this study aimed to enhance the mechanical performance of hyaluronic acid (HA)-based microneedles (MNs), one of the most commonly used DMN systems. We introduced in situ precipitation of silica nanoparticles (Si) into the HA matrix in conjunction with conventional micromolding. The precipitated silica nanoparticles were uniformly distributed, forming an interconnected network within the HA matrix. Experimental results demonstrated that the mechanical properties of the HA–Si composite MNs with up to 20 vol% Si significantly improved, leading to higher penetration efficiency compared to pure HA MNs, while maintaining structural integrity without any critical defects. The composite MNs also showed reduced degradation rates and preserved their drug delivery capabilities and biocompatibility. Thus, the developed HA–Si composite MNs present a promising solution for efficient transdermal drug delivery and address the mechanical limitations inherent in DMN systems. Statement of significanceHA–Si composite dissolving microneedle (DMN) systems were successfully fabricated through in situ precipitation and conventional micromolding processes. The precipitated silica nanoparticles formed an interconnected network within the HA matrix, ranging in size from 25 to 230 nm. The optimal silica content for HA–Si composite MN systems should be up to 20 % by volume to maintain structural integrity and mechanical properties. HA–Si composite MNs with up to 20 % Si showed improved penetration efficiency and reduced degradation rates compared to pure HA MNs, thereby expanding the operational window. The HA–Si composite MNs retained good drug delivery capabilities and biocompatibility.

Superior separation of industrial oil-in-water emulsions utilizing surface patterned isotropic PES membranes

Developing polymeric membranes for oily wastewater treatment has attracted great interest over the last few years. However, the low permeance and poor fouling resistance are considered the most challenging issues. Introducing topographic patterns on the membrane surface to increase active area and surface roughness is one practical strategy for reducing membrane fouling. Here, isotropic polyethersulfone (PES) membranes with line patterns and continuous sponge-like porous structure were prepared using phase separation micro-molding processes. Various techniques were used to characterize the morphologies and physicochemical properties of the as-prepared membranes. The surface wettability of the membranes was evaluated by measuring contact angle of a water drop in air and of industrial crude oil under water. The as-prepared membranes separation and antifouling performance were assessed using water permeance, oil rejection, and flux recovery ratio after emulsion filtration. The results showed that the patterned PES membrane has superior hydrophilic and antifouling capabilities, with a lower static water contact angle (CA) of 32° as compared to a flat PES membrane (CA = 39°). Furthermore, the patterned membrane had pure water permeance (PWP) of 8036 ± 65 L·h−1·m−2·bar−1, which was ∼ 68 % greater than that of the flat PES membrane. This is mainly attributable to the discernible increase in the membrane pore size distribution and the enhancement in membrane surface hydrophilicity due to the increase in surface roughness as a result of micro-patterning. The patterned membranes showed superior separation efficiency (>99.0 %) and permeance (7031 ± 65 L·h−1·m−2·bar−1) for the oil-in-water emulsion of 0.1 g·L−1. At a higher concentration of crude oil-in-water emulsion (50 g·L−1), the patterned PES membranes achieved promising permeance of 90 L/h.m2.bar and 99.9 % rejection. Furthermore, the flux recovery ratio of the patterned membrane exceeded 91 % after three consecutive cycles of dead-end filtration and backwashing with water, demonstrating the benefit of using micro-patterned membranes for treating high concentration and industrial oil-in-water emulsions.

Tuning Power Ultrasound for Enhanced Performance of Thermoplastic Micro-Injection Molding: Principles, Methods, and Performances.

With the wide application of Micro-Electro-Mechanical Systems (MEMSs), especially the rapid development of wearable flexible electronics technology, the efficient production of micro-parts with thermoplastic polymers will be the core technology of the harvesting market. However, it is significantly restrained by the limitations of the traditional micro-injection-molding (MIM) process, such as replication fidelity, material utilization, and energy consumption. Currently, the increasing investigation has been focused on the ultrasonic-assisted micro-injection molding (UAMIM) and ultrasonic plasticization micro-injection molding (UPMIM), which has the advantages of new plasticization principle, high replication fidelity, and cost-effectiveness. The aim of this review is to present the latest research activities on the action mechanism of power ultrasound in various polymer micro-molding processes. At the beginning of this review, the physical changes, chemical changes, and morphological evolution mechanism of various thermoplastic polymers under different application modes of ultrasonic energy field are introduced. Subsequently, the process principles, characteristics, and latest developments of UAMIM and UPMIM are scientifically summarized. Particularly, some representative performance advantages of different polymers based on ultrasonic plasticization are further exemplified with a deeper understanding of polymer–MIM relationships. Finally, the challenges and opportunities of power ultrasound in MIM are prospected, such as the mechanism understanding and commercial application.

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.

Digital Manufacturing for Microfluidics.

The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. As a result, the dissemination of microfluidic technology-and its impact on society-is in jeopardy. Digital manufacturing (DM) refers to a family of computer-centered processes that integrate digital three-dimensional (3D) designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. In this article, we review and discuss the various printer types, resolution, biocompatibility issues, DM microfluidic designs, and the bright future ahead for this promising, fertile field.

Creation of film-free freestanding 3D microstructures by aligned mask micromolding

There are established macroscale fabrication methods to create parts of virtually any shape or size; but for components in the microscale range (thousands to tens of microns) there is a dearth of options for making 3D parts at high enough throughput to make them practical. Here we use traditional photolithography with an aligned mask micromolding method to fabricate freestanding 3D microstructures that can be used as components of microrobotics and microfluidics devices for biomedical applications. The overall goal of this research is to create novel micromolding processes that are capable of creating defect-free microscale structures with controllable 3D geometry, a variety of material properties, and high fabrication throughput. While some methods are available that are capable of meeting a few of these goals, nothing exists in the current microfabrication repertoire that can accomplish all simultaneously.

Digital Manufacturing of Selective Porous Barriers in Microchannels Using Multi-Material Stereolithography.

We have developed a sequential stereolithographic co-printing process using two different resins for fabricating porous barriers in microfluidic devices. We 3D-printed microfluidic channels with a resin made of poly(ethylene glycol) diacrylate (MW = 258) (PEG-DA-258), a UV photoinitiator, and a UV sensitizer. The porous barriers were created within the microchannels in a different resin made of either PEG-DA (MW = 575) (PEG-DA-575) or 40% (w/w in water) PEG-DA (MW = 700) (40% PEG-DA-700). We showed selective hydrogen ion diffusion across a 3D-printed PEG-DA-575 porous barrier in a cross-channel diffusion chip by observing color changes in phenol red, a pH indicator. We also demonstrated the diffusion of fluorescein across a 3D-printed 40% PEG-DA-700 porous barrier in a symmetric-channel diffusion chip by measuring fluorescence intensity changes across the porous barrier. Creating microfluidic chips with integrated porous barriers using a semi-automated 3D printing process shortens the design and processing time, avoids assembly and bonding complications, and reduces manufacturing costs compared to micromolding processes. We believe that our digital manufacturing method for fabricating selective porous barriers provides an inexpensive, simple, convenient and reproducible route to molecule delivery in the fields of molecular filtration and cell-based microdevices.

A simple method for producing freestanding 3D microstructures by integrated photomask micromolding

Freestanding three-dimensional (3D) microstructures are widely used in micro-electro-mechanical system (MEMS) applications or can function as microdevices themselves. However, microfabrication methods for freestanding 3D microstructures have limitations in shape, size, cost, and mass production, etc. In this work, integrated photomask micromolding is demonstrated, which uses a portable UV light source and chrome glass micromolding to fabricate 3D microstructures without alignment. Specifically, a chrome layer on one side of the glass micromold shields the excess filling SU-8 photoresist from UV exposure and only the SU-8 photoresist in mold cavities is crosslinked. The 3D microstructures produced using this method have very high dimensional accuracy and the profile error is approximately 1.5%. This method can be used with features of virtually any size and shape and can be integrated into highly-parallel micromolding processes and has potential for MEMS applications.

Fabrication of a Polymeric Ridge Waveguide Filter Using a Replication Process

The traditional wavelength filter only have one face of grating, the gratings length must be long enough to obtain good filtering result, so the filter device can not be made to a small size. We describe a procedure for rapidly and conveniently prototyping Bragg grating on the three side of the polymer ridge waveguide using holographic interferometry and micro-molding processes. In this experiment, the master of the periodic structure was created on an i-line submicrometer positive photoresist film by a holographic interference using a He-Cd (325nm) laser. A subsequent mold using polydimethylsiloxane (PDMS) polymer was cast against this master and used as a stamp to transfer the grating pattern onto a UV cure epoxy. The technique shows accurate control for the transferring of a gratings period and depth. It can obtain the filtering result with very short grating length which means that it can be made with a small filtering device.

Development of Roll Micromold System via Deep X-ray Lithography and Metal Electroforming Processes

In the present study, a novel roll-shaped micromold system, referred to as a roll micromold system (RMS), is proposed and developed by a deep X-ray lithography process and subsequent electroforming. The developed RMS consists of several cylindrical roll micromold modules (RMMs) including various cross-sectional microstructures along their circumferential surface. RMMs with different microstructures are assembled to construct the RMS, which can be utilized in roll-type micromolding processes for the continuous replication of more complicated microstructured sheets and/or films. As a representative example of an RMS, several copper RMMs having triangular, rectangular, and trapezoidal microstructures on their circumferential surface were precisely fabricated. The RMS was successfully obtained by assembling such RMMs. A rolling experiment utilizing the assembled RMS was also carried out to verify its usefulness.

Fabrication of high-resolution periodical structure on polymer waveguides using a replication process

This paper describes a procedure to replicate a polymeric wavelength filter. In this work, the grating structure on a polymer is fabricated first using holographic interferometry and micro-molding processes. The polymeric wavelength filters are produced by a two-step molding process where the master mold is first formed on a negative tone photoresist and subsequently transferred to a PDMS mold; following this step, the PDMS silicon rubber mold was used as a stamp to transfer the pattern of the polymeric wavelength filters onto a UV cure epoxy. Initial results show good pattern transfer in physical shape. At the Bragg wavelength, a transmission dip of -15.5 dB relative to the -3dB background insertion loss and a 3-dB-transmission bandwidth of ?6nm were obtained from the device.

Mechanical properties of epitaxial 3C silicon carbide thin films

Microscale tensile specimens of epitaxial 3C silicon carbide (3C-SiC) thin films were fabricated on Si substrates and tested to provide measurements of strength and elastic modulus. Samples were fabricated using both micromolding and reactive ion etching (RIE) processes to pattern the 3C-SiC films. All specimens were on the (100) plane with a <110> tensile direction. Testing was performed on a microsample tensile testing machine previously used on other materials. The samples had a thickness of 0.5 to 2 /spl mu/m, a gauge length of 4 mm, and a minimum width of 600 /spl mu/m. Testing results show an average strength of 1.19 /spl plusmn/ 0.53 GPa and 1.65 /spl plusmn/ 0.39 GPa for micromolded and RIE patterned specimens, respectively. The elastic modulus was measured to be 424 /spl plusmn/ 44 GPa, which was consistent with but slightly lower than the elastic modulus calculated with single crystal elastic constants found by ab initio calculations.

Fabrication of a high-resolution periodical structure using a replication process

We describe a procedure for rapidly and conveniently prototyping a periodic structure at submicrometer order using holographic interferometry and micro-molding processes. In this experiment, the master of the periodic structure was created on an i-line submicrometer positive photoresist film by a holographic interference using a He-Cd (325nm) laser. A subsequent mold using polydimethylsiloxane (PDMS) polymer was cast against this master and used as a stamp to transfer the grating pattern onto a UV cure epoxy. The technique shows accurate control for the transferring of a grating's period and depth. The grating pattern on the epoxy produced by the PDMS mold shows an average of less than 2% error in the grating period and an average of 15% error in depth reproduction.