Combination of Material Processing and Characterization Methods for Miniaturization of Field-Effect Gas Sensor.

The technological approach for the low-scale production of field-effect gas sensors as electronic components for use in non-lab ambient environments is described. In this work, in addition to the mechanical protection of a gas-sensitive structure, an emphasis was also placed on the very topical issue of thermal stabilization around the one temperature point, even if it is several degrees higher than the surrounding one, which will probably also be useful for any type of application for many types of field-effect sensors. Considerable attention was paid to the characterization of the results obtained by various invasive and non-invasive methods for diagnosing the manufactured construction. The technology described in this article occupies an intermediate position between laboratory samples tested in clean rooms with stable ambient atmospheres, and experimental and small-scale production sensors designed for real operating conditions to solve the narrow application of measuring low concentrations of hydrogen.

Exploring Endothelial Expansion on a Chip.

Angiogenesis is the development of new blood vessels from the existing vasculature. Its malfunction leads to the development of cancers and cardiovascular diseases qualified by the WHO as a leading cause of death worldwide. A better understanding of mechanisms regulating physiological and pathological angiogenesis will potentially contribute to developing more effective treatments for those urgent issues. Therefore, the main goal of the following study was to design and manufacture an angiogenesis-on-a-chip microplatform, including cylindrical microvessels created by Viscous Finger Patterning (VFP) technique and seeded with HUVECs. While optimizing the VFP procedure, we have observed that lumen's diameter decreases with a diminution of the droplet's volume. The influence of Vascular Endothelial Growth Factor (VEGF) with a concentration of 5, 25, 50, and 100 ng/mL on the migration of HUVECs was assessed. VEGF's solution with concentrations varying from 5 to 50 ng/mL reveals high angiogenic potential. The spatial arrangement of cells and their morphology were visualized by fluorescence and confocal microscopy. Migration of HUVECs toward loaded angiogenic stimuli has been initiated after overnight incubation. This research is the basis for developing more complex vascularized multi-organ-on-a-chip microsystems that could potentially be used for drug screening.

Polycarbonate Heat Molding for Soft Lithography.

Soft lithography enables rapid microfabrication of many types of microsystems by replica molding elastomers into master molds. However, master molds can be very costly, hard to fabricate, vulnerable to damage, and have limited casting life. Here, an approach for the multiplication of master molds into monolithic thermoplastic sheets for further soft lithographic fabrication is introduced. The technique is tested with master molds fabricated through photolithography, mechanical micromilling as well as 3D printing, and the results are demonstrated. Microstructures with submicron feature sizes and high aspect ratios are successfully copied. The copying fidelity of the technique is quantitatively characterized and the microfluidic devices fabricated through this technique are functionally tested. This approach is also used to combine different master molds with up to 19 unique geometries into a single monolithic copy mold in a single step displaying the effectiveness of the copying technique over a large footprint area to scale up the microfabrication. This microfabrication technique can be performed outside the cleanroom without using any sophisticated equipment, suggesting a simple way for high-throughput rigid monolithic mold fabrication that can be used in analytical chemistry studies, biomedical research, and microelectromechanical systems.

Microstructure-Based Fiber-To-Chip Coupling of Polymer Planar Bragg Gratings for Harsh Environment Applications.

This article proposes and demonstrates a robust microstructure-based fiber-to-chip coupling scheme for planar Bragg grating devices. A polymer planar Bragg grating substrate is manufactured and microstructured by means of a micromilling process, while the respective photonic structures are generated by employing a sophisticated single-writing UV-exposure method. A stripped standard single mode fiber is inserted into the microstructure, which is filled with a UV-curable adhesive, and aligned with the integrated waveguide. After curing, final sensor assembly and thermal treatment, the proposed coupling scheme is capable of withstanding pressures up to 10 bar, at room temperature, and pressures up to 7.5 bar at an elevated temperature of 120 °C. Additionally, the coupling scheme is exceedingly robust towards tensile forces, limited only by the tensile strength of the employed single mode fiber. Due to its outstanding robustness, the coupling scheme enables the application of planar Bragg grating devices in harsh environments. This fact is underlined by integrating a microstructure-coupled photonic device into the center of a commercial-grade carbon fiber-reinforced polymer specimen. After its integration, the polymer-based Bragg grating sensor still exhibits a reflection peak with a dynamic range of 24 dB, and can thus be employed for sensing purposes.

A micromilled microgrid sensor with delaminated MXene-bismuth nanocomposite assembly for simultaneous electrochemical detection of lead(II), cadmium(II) and zinc(II).

A delaminated MXene-bismuth (Bi@d-Ti3C2) nanocomposite was synthesized for the construction of a microgrid electrochemical sensor via mechanical milling. The Bi@d-Ti3C2 nanocomposite was synthesized by accumulation of Bi(III) on the surface of delaminated Ti3C2 nanosheets through electrostatic attraction and subsequent in-situ growth of bismuth nanorods. Under optimized experimental conditions, the sensor exhibits (a) linear responses to Pb(II), Cd(II) and Zn(II) in the concentration range from 1 to 20 µg L-1, (b) well separated peak potentials at -0.54 V, -0.76 V and - 1.15 V vs. Ag/AgCl, (c) sensitivities of 0.98, 0.84 and 0.60 µA L µg-1, and (d) detection limits of 0.2, 0.4 and 0.5 µg L-1, respectively. This performance is attributed to the uniform dispersion of Bi nanorods on electrically conductive delaminated Ti3C2 MXene, and to the enhanced diffusion due to the microgrid structure. Graphical abstractSchematic representation of a microgrid sensor based on delaminated MXene-bismuth (Bi@d-Ti3C2) nanocomposite for the simultaneous electrochemical determination of Pb(II), Cd(II) and Zn(II).

Particle size of milled chokeberry pomace did not influence in vitro cellular absorption and transport efficiencies of anthocyanins, phenolic acids and flavonols.

Industrial chokeberry pomace is very rich in polyphenols. The main focus here lies on the possible relationship between the particle size of chokeberry milled pomace and an enhanced absorption and transport of polyphenols by Caco-2 cells. Wet milling was used to produce materials with particle size distributions in the micrometre and in the sub-micrometre to nanometre ranges starting from chokeberry pomace. Milled materials with about 50% of the particles with a mean size (x50,3) of 223 ± 13 µm (coarse milling) and about 90% of the particles with x50,3 of 160 ± 40 nm (fine milling, sonication) were obtained. None of the milled materials exhibited cytotoxic effects within the tested concentration-ranges. The polyphenol absorption and the transport efficiencies from the fine and the coarse milled materials were similar. Thus, no effect of the particle size upon cellular uptake and transport could be established, but agglomeration of particle during incubation cannot be excluded as the cause. Furthermore, based on polyphenol stability we postulate that direct milling may be applied to valorise the processing by-product from commercial fruit juice production.

Facile and cost-effective production of microscale PDMS architectures using a combined micromilling-replica moulding (µMi-REM) technique.

We describe a cost-effective and simple method to fabricate PDMS-based microfluidic devices by combining micromilling with replica moulding technology. It relies on the following steps: (i) microchannels are milled in a block of acrylic; (ii) low-cost epoxy adhesive resin is poured over the milled acrylic block and allowed to cure; (iii) the solidified resin layer is peeled off the acrylic block and used as a mould for transferring the microchannel architecture onto a PDMS layer; finally (iv) the PDMS layer is plasma bonded to a glass surface. With this method, microscale architectures can be fabricated without the need for advanced technological equipment or laborious and time-consuming intermediate procedures. In this manuscript, we describe and validate the microfabrication procedure, and we illustrate its applicability to emulsion and microbubble production.

Effect of Different Fluids on Rectified Motion of Leidenfrost Droplets on Micro/Sub-Micron Ratchets.

Leidenfrost droplets, liquid droplets placed on a hot flat surface above the Leidenfrost temperature of the liquid, are an interesting model system to understand and achieve frictionless motion of droplets on a surface. Controlled unidirectional motion of otherwise random Leidenfrost droplets can be achieved by replacing the flat surface by a surface with topological ratchets. In this study, we show how an increase in the vapor layer thickness below the Leidenfrost droplet influences the droplet motion for underlying ratchets with various periods ranging from 1.5mm down to 800nm. This was exploited by systematically studying the Leidenfrost droplet motion of various liquids with low boiling points including acetone, isopropanol, and R134a on the aforementioned various ratchets. For all liquids with boiling points lower than water, no unidirectional motion was observed for 800 nm. This indicates that the asymmetric vapor flow beneath the Leidenfrost droplet becomes negligible due to the large vapor layer thickness relative to the ratchet depth. However, unidirectional droplet motion was still observed for the micron and millimeter scale ratchets even when the ratchet surface temperature was increased up to 360°C and 230°C for acetone and isopropanol, respectively. This can be attributed to the insulating property of the thick vapor layer which prevent the droplet from producing more vapor with increasing temperature. We also report the effect of the ratchet period on the droplet motion at room temperature using R134a droplets.

Cleanroom-Free Microfluidic Device for Natural Induction of Hypoxia in 2D and 3D Tumor Models.

Hypoxia is a common and critical feature of solid tumors that contributes to the plasticity and heterogeneity of the cancer cells. Cancer cell populations take on a region-specific adaptation induced by hypoxia, and each cancer cell population will show different levels of sensitivity and resistance to cancer therapeutics. Therefore, a faithful recapitulation of tumor hypoxia that allows for accurate assessments of hypoxia-induced adaptations, heterogeneity, and response to therapy is needed to develop new therapeutic approaches. The existing hypoxic tumor models rely on complex fabrication methods and external gas sources that make them unfavorable for the early-stage screening of new therapeutics. Here, we demonstrate how to establish a cleanroom-free microfluidic device that supports both 2D and 3D hypoxic tumor modeling through natural cancer cell metabolism and confirm the induction of the hypoxic gradient.

Thermal Conductivity Gas Sensors for High-Temperature Applications.

This paper describes a fast and flexible microfabrication method for thermal conductivity gas sensors useful in high-temperature applications. The key parts of the sensor, the microheater and the package, were fabricated from glass-coated platinum wire and the combination of laser micromilling (ablation) of already-sintered monolithic ceramic materials and thick-film screen-printing technologies. The final thermal conductivity gas sensor was fabricated in the form of a complete MEMS device in a metal ceramic package, which could be used as a compact miniaturized surface-mounted device for soldering to standard PCB. Functional test results of the manufactured sensor are presented, demonstrating their full suitability for gas sensing applications and indicating that the obtained parameters are at a level comparable to those of standard industrially produced sensors. The results of the design and optimization principles of applied methods are discussed with regard to possible wider applications in thermal gas sensor prototyping in the future. The advantage of the developed sensors is their ability to operate in air environments under high temperatures of 900 °C and above. The sensor element material and package metallization were insensitive to oxidation compared with classical sensor-solution-based metal-glass packages and silicone MEMS membranes, which exhibit mechanical stress at temperatures above 700 °C.

Tunable In Situ Synthesis of Ultrathin Extracellular Matrix-Derived Membranes in Organ-on-a-Chip Devices.

Thin cell culture membranes in organ-on-a-chip (OOC) devices are used to model a wide range of thin tissues. While early and most current platforms use microporous or fibrous elastomeric or thermoplastic membranes, there is an emerging class of devices using extra-cellular matrix (ECM) protein-based membranes to improve their biological relevance. These ECM-based membranes present physiologically relevant properties, but they are difficult to integrate into OOC devices due to their relative fragility. Additionally, the specialized fabrication methods developed to date make comparison between methods difficult. This work presents the development and characterization of a method to produce ultrathin matrix-derived membranes (UMM) in OOC devices that requires only a preassembled thermoplastic device and a micropipette, decoupling the device and UMM fabrication processes. Control over the thickness and permeability of the UMM is demonstrated, along with integration of the UMM in a device enabling high-resolution on-chip microscopy. The reliability of the UMM fabrication method is leveraged to develop a medium-throughput well-plate format device with 32 independent UMM-integrated samples. Finally, proof-of-concept cell culture experiments are demonstrated. Due to its simplicity and controllability, the presented method has the potential to overcome technical barriers preventing wider adoption of physiologically relevant ECM-based membranes in OOC devices.

Dynamic Modeling for Chatter Analysis in Micro-Milling by Integrating Effects of Centrifugal Force, Gyroscopic Moment, and Tool Runout.

During micro-milling, regenerative chatter will decrease the machining accuracy, destabilize the micro-milling process, shorten the life of the micro-mill, and increase machining failures. Establishing a mathematical model of chatter vibration is essential to suppressing the adverse impact of chatter. The mathematical model must include the dynamic motions of the cutting system with the spindle-holder-tool assembly and tool runout. In this study, an integrated model was developed by considering the centrifugal force induced by rotational speeds, the gyroscopic effect introduced by high speeds, and the tool runout caused by uncertain factors. The tool-tip frequency-response functions (FRFs) obtained by theoretical calculations and the results predicted by simulation experiments were compared to verify the developed model. And stability lobe diagrams (SLDs) and time-domain responses are depicted and analyzed. Furthermore, experiments on tool-tip FRFs and micro-milling were conducted. The results validate the effectiveness of the integrated model, which can calculate the tool-tip FRFs, SLDs, and time responses to analyze chatter stability by considering the centrifugal force, gyroscopic effect, and tool runout.

Jet Electrochemical Micromilling of Ti-6Al-4V Using NaCl-Ethylene Glycol Electrolyte.

Titanium alloys are widely used in aerospace and biomedicine because of their excellent mechanical characteristics, but these properties also make such alloys difficult to cut. Jet electrochemical micromilling (JEMM) is based on the principle of electrochemical anodic dissolution; it has some inherent advantages for the machining of titanium alloy microstructures. However, titanium oxidizes readily, forming an oxide film that impedes a uniform dissolution during electrochemical machining. Therefore, a high voltage and an aqueous NaCl electrolyte are usually used to break the oxide film, which can lead to severe stray corrosion. To overcome this problem, the present study investigated the JEMM of Ti-6Al-4V using a NaCl-ethylene glycol (NaCl-EG) electrolyte. Electrochemical testing showed that Ti-6Al-4V exhibits a better corrosion resistance in the NaCl-EG electrolyte compared to the aqueous NaCl electrolyte, thereby reducing stray corrosion. The localization and surface quality of the grooves were enhanced significantly when using JEMM with a NaCl-EG electrolyte. A multiple-pass strategy was adopted during JEMM to improve the aspect ratio, and the effects of the feed depth and number of passes on the multiple-pass machining performance were investigated. Ultimately, a square annular microstructure with a high geometric dimensional consistency and a smooth surface was obtained via JEMM with multiple passes using the optimal parameters.

Study on the Mechanism of Burr Formation by Simulation and Experiment in Ultrasonic Vibration-Assisted Micromilling.

Due to the strong plasticity of Inconel 718 and the significant size effect of micromachining, a large number of burrs will be produced in traditional processing. The addition of ultrasonic vibration during machining can reduce the burr problem. The mechanism of burr generation in traditional micromilling (TMM) and ultrasonic vibration-assisted micromilling (UVAMM) was analyzed by simulation, and verified by corresponding experiments. It is found that applying high-frequency ultrasonic vibration in the milling feed direction can reduce cutting temperature and cutting force, improve chip breaking ability, and reduce burr formation. When the cutting thickness will reach the minimum cutting thickness hmin, the chip will start to form. When A/ƒz > 1/2, the tracks of the two tool heads start to cut, and the chips are not continuous. Some of the best burr suppression effects were achieved under conditions of low cutting speed (Vc), feed per tooth (ƒz), and large amplitude (A). When A is 6 µm, the size and quantity of burr is the smallest. When ƒz reaches 6 µm, large continuous burrs appear at the top of the groove. The experimental results further confirm the accuracy of the simulation results and provide parameter reference.

Three-Dimensional Displacement Measurement of Micro-Milling Tool Based on Fiber Array Encoding.

The vibration of the micro-milling tool presents a significant chaotic vibration phenomenon, which has a great influence on the tool life and part machining precision, and is one of the basic problems restricting the improvement of machining efficiency and machining accuracy in micro-milling. To overcome the difficulty of the traditional vibration measurement method with the online measurement of micro-milling tool multi-dimensional vibration, a three-dimensional (3D) measurement method of the micro-milling tool is proposed based on multi-fiber array coding, which converts the tool space motion into a decoding process of the optical coding array employing the tool modulating the multi-fiber array encoding. A 6 × 6 optical fiber array was designed, and a 3D motion platform for micro-milling tools was built to verify the characteristics of the optical fiber measurement system. The measurement results show that the measuring accuracy of the system reached 1 µm, and the maximum linear error in x-, y-, and z-direction are 1.5%, 2.58%, and 2.43%, respectively; the tool space motion position measurement results show that the maximum measurement error of the measuring system was 3.4%. The designed system has unique coding characteristics for the tool position in the space of 100 µm3. It provides a new idea and realization means for the online vibration measurement of micro-milling tools.

Cutting-Force Modeling Study on Vibration-Assisted Micro-Milling of Bone Materials.

This study aims to enhance surgical safety and facilitate patient recovery through the investigation of vibration-assisted micro-milling technology for bone-material removal. The primary objective is to reduce cutting force and improve surface quality. Initially, a predictive model is developed to estimate the cutting force during two-dimensional (2D) vibration-assisted micro-milling of bone material. This model takes into account the anisotropic structural characteristics of bone material and the kinematics of the milling tool. Subsequently, an experimental platform is established to validate the accuracy of the cutting-force model for bone material. Micro-milling experiments are conducted on bone materials, with variations in cutting direction, amplitude, and frequency, to assess their impact on cutting force. The experimental results demonstrate that selecting appropriate machining parameters can effectively minimize cutting force in 2D vibration-assisted micro-milling of bone materials. The insights gained from this study provide valuable guidance for determining cutting parameters in vibration-assisted micro-milling of bone materials.

Comparative Analysis of Minimum Chip Thickness, Surface Quality and Burr Formation in Micro-Milling of Wrought and Selective Laser Melted Ti64.

Selective laser melting (SLM) is a three-dimensional (3D) printing process that can manufacture functional parts with complex geometries as an alternative to using traditional processes, such as machining wrought metal. If precision and a high surface finish are required, particularly for creating miniature channels or geometries smaller than 1 mm, the fabricated parts can be further machined. Therefore, micro milling plays a significant role in the production of such miniscule geometries. This experimental study compares the micro machinability of Ti-6Al-4V (Ti64) parts produced via SLM compared with wrought Ti64. The aim is to investigate the effect of micro milling parameters on the resulting cutting forces (Fx, Fy, and Fz), surface roughness (Ra and Rz), and burr width. In the study, a wide range of feed rates was considered to determine the minimum chip thickness. Additionally, the effects of the depth of cut and spindle speed were observed by taking into account four different parameters. The manufacturing method for the Ti64 alloy does not affect the minimum chip thickness (MCT) and the MCT for both the SLM and wrought is 1 µm/tooth. SLM parts exhibit acicular α martensitic grains, which result in higher hardness and tensile strength. This phenomenon prolongs the transition zone of micro-milling for the formation of minimum chip thickness. Additionally, the average cutting force values for SLM and wrought Ti64 fluctuated between 0.072 N and 1.96 N, depending on the micro milling parameters used. Finally, it is worth noting that micro-milled SLM workpieces exhibit lower areal surface roughness than wrought ones.

Process Development for Batch Production of Micro-Milling Tools Made of Silicon Carbide by Means of the Dry Etching Process.

Downsized and complex micro-machining structures have to meet quality requirements concerning geometry and convince through increasing functionality. The development and use of cutting tools in the sub-millimeter range can meet these demands and contribute to the production of intelligent components in biomedical technology, optics or electronics. This article addresses the development of double-edged micro-cutters, which consist of a two-part system of cutter head and shaft. The cutting diameters are between 50 and 200 µm. The silicon carbide cutting heads are manufactured from the solid material using microsystem technology. The substrate used can be structured uniformly via photolithography, which means that 5200 homogeneous micro-milling heads can be produced simultaneously. This novel batch approach represents a contrast to conventionally manufactured micro-milling cutters. The imprint is taken by means of reactive ion etching using a mask made of electroplated nickel. Within this dry etching process, characteristic values such as the etch rate and flank angle of the structures are critical and will be compared in a parameter analysis. At optimal parameters, an anisotropy factor of 0.8 and an etching rate of 0.34 µm/min of the silicon carbide are generated. Finally, the milling heads are diced and joined. In the final machining tests, the functionality is investigated and any signs of wear are evaluated. A tool life of 1500 mm in various materials could be achieved. This and the milling quality achieved are in the range of conventional micro-milling cutters, which gives a positive outlook for further development.

Innovative Fabrication of Hollow Microneedle Arrays Enabling Blood Sampling with a Self-Powered Microfluidic Patch.

Microneedles are gaining a lot of attention in the context of sampling cutaneous biofluids such as capillary blood. Their minimal invasiveness and user-friendliness make them a prominent substitute for venous puncture or finger-pricking. Although the latter is suitable for self-sampling, the impracticality of manual handling and the difficulty of obtaining enough qualitative sample is driving the search for better solutions. In this context, hollow microneedle arrays (HMNAs) are particularly interesting for completely integrating sample-to-answer solutions as they create a duct between the skin and the sampling device. However, the fabrication of sharp-tipped HMNAs with a high aspect ratio (AR) is challenging, especially since a length of ≥1500 µm is desired to reach the blood capillaries. In this paper, we first described a novel two-step fabrication protocol for HMNAs in stainless steel by percussion laser drilling and subsequent micro-milling. The HMNAs were then integrated into a self-powered microfluidic sampling patch, containing a capillary pump which was optimized to generate negative pressure differences up to 40.9 ± 1.8 kPa. The sampling patch was validated in vitro, showing the feasibility of sampling 40 µL of liquid. It is anticipated that our proof-of-concept is a starting point for more sophisticated all-in-one biofluid sampling and point-of-care testing systems.

A Simple Micromilled Microfluidic Impedance Cytometer with Vertical Parallel Electrodes for Cell Viability Analysis.

Microfluidic impedance cytometry has been demonstrated as an effective platform for single cell analysis, taking advantage of microfabricated features and dielectric cell sensing methods. In this study, we present a simple microfluidic device to improve the sensitivity, accuracy, and throughput of single suspension cell viability analysis using vertical sidewall electrodes fabricated by a widely accessible negative manufacturing method. A microchannel milled through a 75 µm platinum wire, which was embedded into poly-methyl-methacrylate (PMMA), created a pair of parallel vertical sidewall platinum electrodes. Jurkat cells were interrogated in a custom low-conductivity buffer (1.2 ± 0.04 mS/cm) to reduce current leakage and increase device sensitivity. Confirmed by live/dead staining and electron microscopy, a single optimum excitation frequency of 2 MHz was identified at which live and dead cells were discriminated based on the disruption in the cell membrane associated with cell death. At this frequency, live cells were found to exhibit changes in the impedance phase with no appreciable change in magnitude, while dead cells displayed the opposite behavior. Correlated with video microscopy, a computational algorithm was created that could identify cell detection events and determine cell viability status by application of a mathematical correlation method.