Fabrication Of Micromolds Research Articles

Massive fabrication of functional hepatic cancer spheroids by micropatterned GelMA hydrogel chip for drug screening

Since hepatic cancer incidence and mortality continue to grow worldwide, it is necessary to develop the biomimetic tumor models for drug development and tumor therapeutics. Cellular spheroids as an excellent simple 3D model can bridge the gap between 2D cell culture and live tissue. In this study, we proposed a biological methacrylated gelatin (GelMA) hydrogel-based microplatform for the massive generation of hepatocellular spheroids and downstream investigation of drug resistance. Micropatterned GelMA hydrogel microwell chip (GHM-chip) with tunable array was easily achieved in standard 24-culture well plates through the micro-molding fabrication strategy. The fabricated GHM-chip induced multicellular self-assembly behavior within the defined topography and further formed spheroidal structure. By regulating cell seeding density and designing microwell size, uniform hepatic cancer spheroids with tunable diameters were obtained in a simplicity, stability and controllable manner. In addition, the screening chemotherapy study of anti-cancer drug was completed through non-destructive recovery of spheroids from the GHM-chip. Beyond that, the recovered functional spheroids have potential application value in various biomedical fields such as tumor biology, pharmacology, and tissue microengineering. Finally, the proposed GHM-chip incorporated into standard cell culture plates with easy to manufacture and operate properties, may be an efficient culture microplatform for cancer research applications.

Fabrication of micro molds by electrodeposition under supergravity field

Nowadays, micro molds have been playing an increasing crucial part in social and industrial fields. As the industry develops, the wear resistance of the micro molds has become more and more important because of its effects on the service life and economic benefit. Improving the hardness of the micro molds was an alternative to enhance its wear resistance, which can be realized by the electrodeposition of Nickel cobalt silicon carbide (Ni–Co/SiC). In this paper, attempts were made to fabricate Ni–Co/SiC micro molds, where supergravity field was introduced to further better the microhardness of the micro molds. The effects of supergravity field on the SiC content, morphology and microhardness of the Ni–Co/SiC micro mold were experimentally investigated. It was demonstrated that under gravity field, grain size is refined, and both the microhardness and morphology were dramatically improved. Finally, Ni–Co/SiC micro-pit molds were successfully obtained using optimized parameters. Production of Ni–Co/SiC micro molds with enhanced microhardness is feasible via electrodeposition under supergravity field.

Rapid high-quality 3D micro-machining by optimised efficient ultrashort laser ablation

Solid-state lasers with pulse duration of 10 ps and radiation wavelength of 1064 nm were used to investigate the laser ablation efficiency dependence on processing parameters: laser fluence (pulse energy and beam spot size), beam scanning speed, pulse repetition rate, and scanned line (hatch) distance for the copper sample. Utilising a 40 W power laser, the highest ablation efficiency of 2.5 µm3/µJ and the ablation rate of 100 µm3/µs with the smallest surface roughness of 0.2 µm was obtained. Three-dimensional (3D) fabrication using a galvanometer scanner and layer-by-layer removal technique with optimal parameters defined for efficient ablation were demonstrated at a rate of 6 mm3/min. Combination of high material removal rate with excellent quality and complex 3D structure formation is in a high interest for mimicking bio-inspired surfaces, micro-mould fabrication and decorative applications.

Fabrication of micro punching mold for micro complex shape part by micro EDM

Micro punching process is suitable for mass production of micro parts. It is a challenge to fabricate micro punching mold with complex cross-sectional shape on-machine. The micro punching system’s structure design has to meet the requirement of large punching force. In this study, a micro punching system has been developed with a micro electrical discharge machining (EDM) module. A series of machining operations, from the fabrication of micro molds to punching, have been completed with no secondary clamping error. The micro die and reversed electrode are prepared using micro EDM milling. The micro punch is fabricated using reversed electrode. The punching clearance is around 11 μm. Complex shape punched holes and blanked parts have been successfully fabricated on copper, brass, 304 stainless steel, and 3J21 alloy. After punching, there was no damage on the edges of micro die and micro punch. The key dimensional error of blanked part varies by different materials, which is less than 2.5 μm.

Toward Soft Micro Bio Robots for Cellular and Chemical Delivery

A major driving force propelling the evolution of micrometer and millimeter scale robots is their eventual use in biological environments. Many advancements to microscale robotic technologies have shown that these small scale robots are well-suited for use in environments in which cells and cellular functions require physical manipulation or reprogramming. More specifically, microscale robots are poised for use in the delivery of small molecules, DNA vectors, and proteins which can edit cellular machinery and probe cell signaling systems. In this work, we explore a unique approach to fabricate magnetic millimeter scale robots composed of a biological substrate. We introduce a micromolding fabrication technique in which we manufacture helical structures, which are propelled via uniform rotating magnetic fields. We demonstrate and characterize the swimming capabilities of this robot in media spanning orders of magnitude in viscosities at a range of rotational magnetic field frequencies. Our ability to operate in low Reynolds number environments shows that our system is also relevant to microscale robots. Furthermore, we demonstrate the robot's inherent biocompatibility by establishing our ability to functionalize this robot with living cells and chemicals such that it can be used for biodelivery or to perform on-board biological experiments.

3D Printing of Molds for Soft Lithography

Microfabrication of PDMS based microfluidic devices involves fabrication of micromolds which need expensive infrastructure, such as clean room, photolithography equipment, photoresists, substrates, masks etc. In this paper, we present fabrication of micromolds using three dimension (3D) printing for soft lithography [1, 2]. By employing 3D printing technology overcomes the challenges posed by time consuming and difficult to manufacture, with state of the art 2-D MEMS fabrication technology [3]. Compared to the conventional method of microfabrication, 3D printed mold can be processed more rapidly, augment use of materials, intricate design which is challenging by photolithography [4,5]. Here, we designed and fabricated micro features using binder jetting printer (Objet30 Pro) and photopolymer jetting printer (Formlabs Form 2). Objet30 Pro uses the technique of depositing adhesive liquid onto the powder photopolymer on the build tray. Binding process between the powdered particles make a solid structure. During the printing of master no support structures where used. The master was also printed using the deposition of photopolymer using the Formlabs Form 2 printer. Concept behind the fabrication is curing the photopolymer by UV light which is deposited pointwise layer-by layer. Since, the fabrication of the master is done in slices the surface of the master was rutted which gave bumpy replication but, were able to print the feature (Round trench, Hexagonal trench) size of 200μm (Fig 1 and 2). Mold fabricated using the Objet30 pro printer gave fine structures with resolution of 300μm in depth and feature size of 500μm were printed flawless. This technique forms a 3D printed structure by holding the particles and does not require support structure.

Fabrication of Si Micro Mold via Tribo-Nanolithography Using Micro Polycrystalline Diamond Cantilever Tool.

A direct mechanical nanomachining, tribo-nanolithography (TNL), has been developed to fabricate micro mold on Si substrate in mechanical milling mode. An atomic force microscope (AFM) tip is replaced by a lab-made Si cantilever with a polycrystalline diamond (PCD) tool. Mechanical cutting by PCD tool enables simple fabrication of micro molds with several tens of nanometers depth. Machined cavities of the Si substrate are prepared as a master mold for additional micro molding using polydimethylsiloxane (PDMS). Micro cavities are successfully duplicated in positive patterns similar to soft lithography. Normal loads of cantilever and AFM topographical images are used to discuss micro mold and micro molding characteristics.

3D Printing of Micromolds and Microfluidic Devices

Over the past 30 years there has been a steady increase in interest in polymeric microfluidics and lab-on-a-chip technologies. The global microfluidics market is projected to reach USD 8.78 Billion by 2021 from USD 3.65 Billion in 2015, at a CAGR of 19.2% during the forecast period (2016 to 2021) [1]. While many polymers have been employed to realize microfluidic devices, polydimethylsiloxane (PDMS), a silicone based elastomer, has been widely used because of its biocompatibility, low cost, low toxicity, high oxidative and thermal stability, optical transparent, low permeability to water, low electrical conductivity, and ease of micropatterning [2,3, 4,5,6,7]. However, microfabrication of PDMS based microfluidic devices involves fabrication of micromolds which need expenisve infrastruce, such as clean room, photolithography equipment, masks etc. [8, 9, 10, 11, 12, 13]. Previously we had presented 3-D printing of complex MEMS structures [14] and other devices [15,16]. In this paper, we present fabrication of microfluidic molds and devices by employing 3D printing technology that are otherwise time consuming and difficult to manufacture with state of the art 2-D MEMS fabrication technology. Figure 1 shows optical micrograph of 3D printed micromold channels.

Photolithography and micromolding techniques for the realization of 3D polycaprolactone scaffolds for tissue engineering applications

Material science, cell biology, and engineering are all part of the research field of tissue engineering. It is the application of knowledge, methods and instrumentations of engineering and life science to the development of biocompatible solutions for repair and/or replace tissues and damaged organs.Last generation microfabrication technologies utilizing natural and synthetic biomaterials allow the realization of scaffolds resembling tissue-like structures as skin, brain, bones, muscles, cartilage and blood vessels.In this work we describe an effective and simple micromolding fabrication process allowing the realization of 3D polycaprolactone (PCL) scaffold for human neural stem cells (hNSC) culture. Scanning Electron Microscopy has been used to investigate the micro and nano features characterizing the surface of the device. Immunofluorescence analysis showed how, after seeding cells onto the substrate, healthy astrocytes grew up in a well-organized 3D network. Thus, we proposed this effective fabrication method for the production of nanopatterned PCL pillared scaffold providing a biomimetic environment for the growth of hNSC, a promising and efficient means for future applications in tissue engineering and regenerative medicine.

Development, Characterization and Cell Cultural Response of 3D Biocompatible Micro-Patterned Poly-ε-Caprolactone Scaffolds Designed and Fabricated Integrating Lithography and Micromolding Fabrication Techniques

Scaffold design and fabrication are very important subjects for biomaterial, tissue engineering and regenerative medicine research playing a unique role in tissue regeneration and repair. Among synthetic biomaterials Poly-e- Caprolactone (PCL) is very attractive bioresorbable polyester due to its high permeability, biodegradability and capacity to be blended with other biopolymers. Thanks to its ability to naturally degrade in tissues, PCL has a great potential as a new material for implantable biomedical micro devices. This work focuses on the establishment of a micro fabrication process, by integrating lithography and micromolding fabrication techniques, for the realization of 3D microstructure PCL devices. Scaffold surface exhibits a combination in the patterned length scale; cylindrical pillars of 10 μm height and 10 μm diameter are arranged in a hexagonal lattice with periodicity of 30 μm and their sidewalls are nano-sculptured, with a regular pattern of grooves leading to a spatial modulation in the z direction. In order to demonstrate that these biocompatible pillared PCL substrates are suitable for a proper cell growth, NIH/3T3 mouse embryonic fibroblasts were seeded on them and cells key adhesion parameters were evaluated. Scanning Electron Microscopy and immunofluorescence analysis were carried out to check cell survival, proliferation and adhesion; cells growing on the PCL substrates appeared healthy and formed a well-developed network in close contact with the micro and nano features of the pillared surface. Those 3D scaffolds could be a promising solution for a wide range of applications within tissue engineering and regenerative medicine applications.

Dielectric elastomer actuators fabricated using a micro-molding process

All-polymer dielectric elastomer actuators have been manufactured using a micro-molding fabrication process. The actuators are multilayer beams made of three conductive and two dielectric elastomer layers. By applying an electrical potential between two of the neighboring conductive electrodes, a stress is generated, which leads to an asymmetric axial strain and, therefore, bending. Bidirectional actuation is achieved by changing the pair of electrodes across which the potential is applied. A 100 μm wide, 40 μm thick, and 1000 μm long actuator demonstrated tip displacement as high as 318 μm at 1.1 kV with an electrical power consumption of 10 μW. Experimental results validate a two-dimensional ANSYS model that is also used to explore the effects of further decreasing layer thickness and relative electrode thickness on DEA performance.

Numerical simulation of aluminum alloy 6061 micro-mold fabrication for the production of polymeric microstructures by micro-hot-embossing

Micro-molds play an important role in the manufacturing process of polymeric micro-devices, e.g. microfluidic devices, as they determine the product quality and the overall production cost. We report here the applicability of a large-deformation, high-temperature, isotropic elastic-viscoplasticity model for the prediction of micron-scale hot-embossing of AA6061. The material parameters in the constitutive model were determined by fitting the stress–strain curves from compression tests at various temperatures and strain rates. The constitutive theory was implemented in a finite element program, and the numerical simulation capability was validated by predicting the response of AA6061 in some representative macro-scale experiments; these experiments had not been used for the determination of the material parameters in the constitutive model. Additional micron-scale hot-embossing experiments on AA6061 were conducted, and by comparing the numerical simulation results to the corresponding physical experiments, we demonstrate that the deformation evolution of AA6061 during micro-hot-embossing is well predicted. The constitutive model and its numerical implementation open the possibility of optimizing the process of making micro-molds for microfluidic devices from AA6061.

Non-bioengineered silk gland fibroin micromolded matrices to study cell-surface interactions

Micropatterning/micromolding of protein molecules has played a significant role in developing biosensors, micro arrays, and tissue engineering devices for cellular investigations. Relevantly, there have been ample scopes for silk to be used as natural biomaterial in tissue engineering applications due to its attractive properties such as slow-controllable degradation, mechanical robustness, and inherent biocompatibility. In this paper, we report the fabrication of micromolded silk fibroin matrices, which have essentially been utilized to study cell-surface interactions. Fibroin protein has been isolated from the silk glands of nonmulberry Indian tropical tasar silkworms, Antheraea mylitta. The surface uniformity has been investigated using atomic force microscopy following the fabrication of silk micromolds. Subsequently, cellular interactions in terms of cell attachment, spreading, mitochondrial activity and proliferation have been studied in vitro using feline fibroblasts. Results have indicated a long term stability of patterns in micromolded silk matrices and negligible swelling. The versatility of described silk dissolution method coupled with ability to process large amount of silk protein into micromolded matrices and controllable surface topology may augment the desirability of silk fibroin as a natural biomaterial for bioengineering and biotechnological applications.

Rapid fabrication of polymethylmethacrylate micromold masters using a hot intrusion process

A method for rapid fabrication of mold masters for soft-molding of polydimethylsiloxane (PDMS) microfluidic devices is successfully developed and tested. The method involves laser micromachining and a hot-intrusion process, and produces mold masters from polymethylmethacrylate (PMMA) substrates. A metallic mask with microchannel line features of various widths (25 to 200 µm) is initially created by laser micromachining a 75-µm-thick brass sheet. Under the hot-intrusion process, a 2-mm-thick solid PMMA substrate is then heated and molded under pressure to force the softened material through the shaped microfeatures in the mask. The height of the extruded microrelief is determined by the pressure, temperature, and time profile of the hot-intrusion process. A mathematical model that characterizes the rapid fabrication process and enables the operator to select appropriate process parameters is described. The derived empirical model is based on experimental observations where extruded microrelief heights were varied from 5 to 75 µm with aspect ratios from 0.1 to 0.46, and radii of the extruded profile from 12 to 270 µm. The proposed model is developed to describe the relationship between key process parameters and the extruded heights of the microreliefs. Furthermore, the model provides the operator with simple guidelines for selecting the process parameters. An example of PDMS microfluidic devices replicated by the rapid micromold fabrication methodology is presented to illustrate the quality of the resultant features of microchannels.

Fabrication of micro mold for hot-embossing of polyimide microfluidic platform by using electron beam lithography combined with inductively coupled plasma

This study describes the fabrication of Si molds by using electron beam lithography (EBL) combined with inductively coupled plasma (ICP) etching and its application to the hot-emboss of polyimide (PI) microfluidic platform. The dynamic mechanical thermal properties and the formability of a polyimide film were investigated as a function of temperature by dynamic mechanical thermal analysis (DMTA) and hot-embossing tests. Based on the results, the microfluidic channel could be replicated on PI surface with good fidelity by hot-embossing with the Si mold structured by using EBL combined with ICP etching.

Ablation and cutting of silicon wafer and micro-mold fabrication using femtosecond laser pulses

Femtosecond laser micromachining of silicon wafer at a relatively higher energy fluence level (>50 J/cm2) is investigated. Laser ablating spots and cutting kerfs are examined by means of charge coupled device camera and scanning electron microscopy. The area of ablated spots increases linearly with increasing the shot number from 1 to 16 and shows saturation with the shot number exceeding 16. Results also show that the area of ablated spots increases with increasing the pulse energy. The widths of cutting kerfs are nearly proportional to pulse energies, and are independent of feed speeds in our experiment. Based on the ablation and cutting, a micro-mold for microelectromechanical system application is fabricated with an accuracy of ∼1 μm at a pulse energy of 240 μJ and a feed speed of 300 μm/s in 6 min.

Micro-mould fabrication for a micro-gear via vacuum casting

A micro-mould fabrication method based on vacuum casting was developed and its functionality and reproducibility were demonstrated. The micro-components used in this study were SU-8 photoresist micro-gears fabricated by UV photolithography. These micro-gears served as the master patterns from which silicone rubber micro-mould cavities were fabricated with the use of the vacuum casting technology. The process parameters that had an influence on the quality of the micro-mould cavities were identified and optimised. Using the optimised process parameters resulted in high fidelity silicone rubber micro-mould cavities at high resolutions. Dimensional analysis was carried out using white light interferometry. It was found that all the micro-gear cavities in the micro-moulds were dimensionally accurate and consistent to the master gear, with a dimension deviation less than 3% of the respective dimensions. Micro-casting was also carried out using the silicone rubber moulds. Micro-gears were successfully transferred from the silicone rubber moulds into PU resin and wax pieces under vacuum conditions, thereby demonstrating that the micro-mould fabricated was capable of producing functional micro-parts that were able to replicate micro-features.

Fabrication of micro-mold for glass embossing using focused ion beam, femto-second laser, eximer laser and dicing techniques

Abstract Various nano-/micro-structuring methods, including focused ion beam (FIB), femto-second laser, KrF eximer laser and dicing techniques, were used to fabricate glassy carbon (GC) micro-molds and were characterized in terms of the process rate, the roughness and the shape of machined structure. The combination of femto-second laser ablation with subsequent FIB milling provided a possibility for the rapid fabrication of high quality micro-structures on a wide surface area. Obtained molds were applied to the hot-emboss process of glasses to investigate process conditions needed for the replication of structures with various geometries and dimensions.

Molding ceramic microstructures on flat and curved surfaces with and without embedded carbon nanotubes

This paper explores micromolding fabrication of alumina ceramic microstructures on flat and curved surfaces, the transfer of carbon nanotube (CNT) micropatterns into the ceramic and oxidation inhibition of these CNTs through ceramic encapsulation. Microstructured master mold templates were fabricated from etched silicon, thermally embossed sacrificial polymer and flexible polydimethylsiloxane (PDMS). The polymer templates were themselves made from silicon masters. Thus, once the master is produced, no further access to a microfabrication facility is required. Using the flexible PDMS molds, ceramic structures with mm scale curvature having microstructures on either the inside or the outside of the curved macrostructure were fabricated. It was possible to embed CNTs into the ceramic microstructures. To do this, micropatterned CNTs on silicon were transferred to ceramic via vacuum molding. Multilayered micropatterned CNT–ceramic devices were fabricated, and CNT electrical traces were encapsulated with ceramic to inhibit oxidation. During oxidation trials, encapsulated CNT traces showed an increase in resistance that was 62% less than those that were not encapsulated. The processes described here could allow fabrication of inexpensive 3D ceramic microstructures suitable for high temperature and harsh chemical environments.

Continuously variable mixing-ratio micromixer with elastomer valves

We report a self-contained microfluidic alternate flow injection mixer (AFIM) employing piezoelectrically actuated, PDMS seal-valves to control injection. AFIMs employ pulsatile injection of liquids to enhance interface surface generation. By allowing control of pulse-volume proportionality by variation of the duty-cycle of the valve control signals, continuously variable ratio mixing is achieved without external fluid control components. Mixing is discussed in the context of ‘rate of new surface generation’, thus allowing comparison with laminating mixer designs. The prototype mixer employs a simple micromould fabrication technique to minimize reversible elastomer valve-seal adhesion and hence allow correct valve operation. The resulting device has been characterized over a range of mixing ratios.