Micromachines — Open Access Journal

This study experimentally analyses the binding characteristics of analytes mixed in liquid samples flowing along a micro-channel to the receptor fixed on the wall of the micro-channel to provide design tools and data for a microfluidic-based biosensor. The binding or detection characteristics are analyzed experimentally by counting the number of analytes bound to the receptor, with sample analyte concentration, sample flow rate, and the position of the receptor along the micro-channel length as the main variables. A mathematical model is also proposed to predict the number of analytes transported and bound to the receptor based on a probability density function for Brownian motion. The coefficient in the mathematical model is obtained by using a dimensionless mathematical model and the experimental results. The coefficient remains valid for all different conditions of the sample analyte concentration, flow rate, and the position of the receptor, which implies the possibility of deriving a generalized model. Based on the mathematical model derived from mathematical and experimental analysis on the detection characteristics of the microfluidic-based biosensor depending on previously mentioned variables and the height of the micro-channel, this study suggests a design for a microfluidic-based biosensor by predicting the binding efficiency according to the channel height. The results show the binding efficiency increases as the flow rate decreases and as the receptor is placed closer to the sample-injecting inlet, but is unaffected by sample concentration. Full article

Energy-autonomous bistable threshold sensor switches have the potential to reduce costs because they do not need any electrical energy supply for monitoring physical quantities, such as relative humidity. In previous work, a bistable beam-like sensor switch with switching hysteresis was manufactured from sheet metal and a partially coated water vapor-sensitive hydrogel (poly(vinyl alcohol)/poly(acryl acid)). Based on the beam theory, a corresponding mechanical model was developed. However, bending plates should be used instead of bending beams to separate the humidity to be measured from the electrical contacts. For this reason, this work deals with the development and realization of a mechanical model based on the plate theory to describe the deflection of a silicon bimorph bending plate partially coated with hydrogel that swells with increasing humidity. For implementing a switching hysteresis a plasma-enhanced chemical vapor deposition silicon dioxide (SiO₂) layer is used, which was deposited and structured on top of the silicon plate. The hydrogel layer itself is patterned on the surface of the bending plate using a stamp technique. To validate the mechanical model, the switching hysteresis of the miniaturized sensor switch was measured optically by a camera measurement device. Full article

Pancreatic cancer (PC) is a global health problem that features a very high mortality rate. The UL16 binding protein 2 (ULBP2) is a new biomarker for PC detection. This study develops a simple, reliable, and inexpensive immunosensor for the detection of the ULBP2 antigen while also investigating the effects of an array configuration of connected sensors and zinc oxide (ZnO) nanoparticles on the immunosensor’s sensitivity. The ULBP2 antibody was immobilized onto the screen-printed carbon electrode (SPCE) surfaces of three different sensors: a simple SPCE (ULBP2-SPCE); an SPCE array, which is a series of identical SPCE connected to each other at different arrangements of rows and columns (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3); and an SPCE combined with ZnO nanoparticles (ULBP2-ZnO/SPCE). Impedance spectrum measurements for the immunosensors to ULBP2 antigen were conducted and compared. According to the result, the array configurations (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3) show an improvement of sensitivity compared to the ULBP2-SPCE alone, but the improvement is not as significant as that of the ULBP2-ZnO/SPCE configuration (ULBP2-ZnO/SPCE > ULBP2-SPCE: 18 times larger). The ULBP2-ZnO/SPCE immunosensor has a low limit of detection (1 pg/mL) and a high sensitivity (332.2 Ω/Log(pg/mL)), excellent linearity (R² = 0.98), good repeatability (coefficients of variation = 5.03%), and is stable in long-term storage (retaining 95% activity after 28 days storage). In an array configuration, the immunosensor has an increased signal-to-noise ratio (ULBP2-SPCE-1x3 > ULBP2-SPCE: 1.5-fold) and sensitivity (ULBP2-SPCE-1x3 > ULBP2-SPCE: 2.6-fold). In conclusion, either the modification with ZnO nanoparticles onto the sensor or the use of an array configuration of sensors can enhance the immunosensor’s sensitivity. In this study, the best immunosensor for detecting ULBP2 antigens is the ULBP2-ZnO/SPCE immunosensor. Full article

Widely accessible, inexpensive, easy-to-use consumer 3D printers, such as desktop stereolithography (SLA) and fused-deposition modeling (FDM) systems are increasingly employed in prototyping and customizing miniaturized fluidic systems for diagnostics and research. However, these 3D printers are generally limited to printing parts made of only one material type, which limits the functionality of the microfluidic devices without additional assembly and bonding steps. Moreover, mating of different materials requires good sealing in such microfluidic devices. Here, we report methods to print hybrid structures comprising a hard, rigid component (clear polymethacrylate polymer) printed by a low-cost SLA printer, and where the first printed part is accurately mated and adhered to a second, soft, flexible component (thermoplastic polyurethane elastomer) printed by an FDM printer. The prescribed mounting and alignment of the first-printed SLA-printed hard component, and its pre-treatment and heating during the second FDM step, can produce leak-free bonds at material interfaces. To demonstrate the utility of such hybrid 3D-printing, we prototype and test three components: i) finger-actuated pump, ii) quick-connect fluid coupler, and iii) nucleic acid amplification test device with screw-type twist sealing for sample introduction. Full article

The sizes of most prokaryotic cells are several microns. It is very difficult to separate cells with similar sizes. A sorter with a contraction–expansion microchannel and applied magnetic field is designed to sort microparticles with diameters of 3, 4 and 5 microns. To evaluate the sorting efficiency of the designed sorter, numerical simulations for calculating the distributions of microparticles with similar sizes were carried out for various magnetic fields, inlet velocities, sheath flow ratios and structural parameters. The numerical results indicate that micro-particles with diameters of 3, 4 and 5 microns can be sorted efficiently in such a sorter within appropriate parameters. Furthermore, it is shown that a bigger particle size and more powerful magnetic field can result in a greater lateral migration of microparticles. The sorting efficiency of microparticles promotes a lower inlet velocity and greater sheath flow ratios. A smaller contraction–expansion ratio can induce a greater space between particle-bands. Finally, the micro particle image velocity (micro-PIV) experiments were conducted to obtain the bandwidths and spaces between particle-bands. The comparisons between the numerical and experimental results show a good agreement and make the validity of the numerical results certain. Full article

Improved in vitro models of human organs for predicting drug efficacy, interactions, and disease modelling are crucially needed to minimize the use of animal models, which inevitably display significant differences from the human disease state and metabolism. Inside the body, cells are organized either in direct contact or in close proximity to other cell types in a tightly controlled architecture that regulates tissue function. To emulate this cellular interface in vitro, an advanced cell culture system is required. In this paper, we describe a set of compartmentalized silicon-based microfluidic chips that enable co-culturing several types of cells in close proximity with enhanced cell-cell interaction. In vivo-like fluid flow into and/or from each compartment, as well as between adjacent compartments, is maintained by micro-engineered porous barriers. This porous structure provides a tool for mimicking the paracrine exchange between cells in the human body. As a demonstrating example, the microfluidic system was tested by culturing human adipose tissue that is infiltrated with immune cells to study the role if the interplay between the two cells in the context of type 2 diabetes. However, the system provides a platform technology for mimicking the structure and function of single- and multi-organ models, which could significantly narrow the gap between in vivo and in vitro conditions. Full article

Fan-out wafer-level packaging (FOWLP) is an interesting platform for Microelectromechanical systems (MEMS) sensor packaging. Employing FOWLP for MEMS sensor packaging has some unique challenges, while some originate merely from the fabrication of redistribution layers (RDL). For instance, it is crucial to protect the delicate structures and fragile membranes during RDL formation. Thus, additive manufacturing (AM) for RDL formation seems to be an auspicious approach, as those challenges are conquered by principle. In this study, by exploiting the benefits of AM, RDLs for fan-out packaging of capacitive micromachined ultrasound transducers (CMUT) were realized via drop-on-demand inkjet printing technology. The long-term reliability of the printed tracks was assessed via temperature cycling tests. The effects of multilayering and implementation of an insulating ramp on the reliability of the conductive tracks were identified. Packaging-induced stresses on CMUT dies were further investigated via laser-Doppler vibrometry (LDV) measurements and the corresponding resonance frequency shift. Conclusively, the bottlenecks of the inkjet-printed RDLs for FOWLP were discussed in detail. Full article

This article conceptualizes and mathematically models a dielectrophoretic microfluidic device with two sets of interdigitated transducer vertical electrodes for separation of a binary heterogeneous mixture of particles based on size; each set of electrodes is located on the sidewalls and independently controllable. To achieve separation in the proposed microfluidic device, the small microparticles are subjected to positive dielectrophoresis and the big microparticles do not experience dielectrophoresis. The mathematical model consists of equations describing the motion of each microparticle, fluid flow profile, and electric voltage and field profiles, and they are solved numerically. The equations of motion take into account the influence of phenomena, such as inertia, drag, dielectrophoresis, gravity, and buoyancy. The model is used for a parametric study to understand the influence of parameters on the performance of the microfluidic device. The parameters studied include applied electric voltages, electrode dimensions, volumetric flow rate, and number of electrodes. The separation efficiency of the big and small microparticles is found to be independent of and dependent on all parameters, respectively. On the other hand, the separation purity of the big and small microparticles is found to be dependent on and independent of all parameters, respectively. The mathematical model is useful in designing the proposed microfluidic device with the desired level of separation efficiency and separation purity. Full article

Vascular endothelial cells form a barrier that blocks the delivery of drugs entering into brain tissue for central nervous system disease treatment. The mechanical responses of vascular endothelial cells play a key role in the progress of drugs passing through the blood–brain barrier. Although nanoindentation experiment by using AFM (Atomic Force Microscopy) has been widely used to investigate the mechanical properties of cells, the particular mechanism that determines the mechanical response of vascular endothelial cells is still poorly understood. In order to overcome this limitation, nanoindentation experiments were performed at different loading rates during the ramp stage to investigate the loading rate effect on the characterization of the mechanical properties of bEnd.3 cells (mouse brain endothelial cell line). Inverse finite element analysis was implemented to determine the mechanical properties of bEnd.3 cells. The loading rate effect appears to be more significant in short-term peak force than that in long-term force. A higher loading rate results in a larger value of elastic modulus of bEnd.3 cells, while some mechanical parameters show ambiguous regulation to the variation of indentation rate. This study provides new insights into the mechanical responses of vascular endothelial cells, which is important for a deeper understanding of the cell mechanobiological mechanism in the blood–brain barrier. Full article

Surface Channel Technology is known as the fabrication platform to make free-hanging microchannels for various microfluidic sensors and actuators. In this technology, thin film metal electrodes, such as platinum or gold, are often used for electrical sensing and actuation purposes. As a result that they are located at the top surface of the microfluidic channels, only topside sensing and actuation is possible. Moreover, in microreactor applications, high temperature degradation of thin film metal layers limits their performance as robust microheaters. In this paper, we report on an innovative idea to make microfluidic devices with integrated silicon sidewall electrodes, and we demonstrate their use as microheaters. This is achieved by modifying the original Surface Channel Technology with optimized mask designs. The modified technology allows to embed heavily-doped bulk silicon electrodes in between the sidewalls of two adjacent free-hanging microfluidic channels. The bulk silicon electrodes have the same electrical properties as the extrinsic silicon substrate. Their cross-sectional geometry and overall dimensions can be designed by optimizing the mask design, hence the resulting resistance of each silicon electrode can be customized. Furthermore, each silicon electrode can be electrically insulated from the silicon substrate. They can be designed with large cross-sectional areas and allow for high power dissipation when used as microheater. A demonstrator device is presented which reached $119.4$ ${}^{\circ }\mathrm{C}$ at a power of $206.9$ $\mathrm{m}$ $\mathrm{W}$ , limited by thermal conduction through the surrounding air. Other potential applications are sensors using the silicon sidewall electrodes as resistive or capacitive readout. Full article

Here, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating tumor cells at a 90 μL/min flow rate when tested on blood spiked with epithelial cell adhesion molecule (EpCAM)-positive Michigan Cancer Foundation-7 (MCF7) cells. Clinical studies were performed using blood samples from non-small cell lung cancer (NSCLC) patients. Varying numbers (2 to 114) of CTCs were found in each NSCLC patient, and serial assessment of CTCs showed that the CTC count correlated with the clinical progression of the disease. The applicability of GenoCTC to different cell surface biomarkers was also validated in a cholangiocarcinoma patient using anti-EPCAM, anti-vimentin, or anti-tyrosine protein kinase MET (c-MET) antibodies. After EPCAM-, vimentin-, or c-MET-positive cells were isolated, CTCs were identified and enumerated by immunocytochemistry using anti-cytokeratin 18 (CK18) and anti-CD45 antibodies. Furthermore, we checked the protein expression of PDL1 and c-MET in CTCs. A study in a cholangiocarcinoma patient showed that the number of CTCs varied depending on the biomarker used, indicating the importance of using multiple biomarkers for CTC isolation and enumeration. Full article

Giant lipid vesicles or liposomes are primarily composed of phospholipids and form a lipid bilayer structurally similar to that of the cell membrane. These vesicles, like living cells, are 5–100 μm in diameter and can be easily observed using an optical microscope. As their biophysical and biochemical properties are similar to those of the cell membrane, they serve as model cell membranes for the investigation of the biophysical or biochemical properties of the lipid bilayer, as well as its dynamics and structure. Investigation of membrane protein functions and enzyme reactions has revealed the presence of soluble or membrane proteins integrated in the giant lipid vesicles. Recent developments in microfluidic technologies and synthetic biology have enabled the development of well-defined artificial cell models with complex reactions based on the giant lipid vesicles. In this review, using microfluidics, the formations of giant lipid vesicles with asymmetric lipid membranes or complex structures have been described. Subsequently, the roles of these biomaterials in the creation of artificial cell models including nanopores, ion channels, and other membrane and soluble proteins have been discussed. Finally, the complex biological functions of giant lipid vesicles reconstituted with various types of biomolecules has been communicated. These complex artificial cell models contribute to the production of minimal cells or protocells for generating valuable or rare biomolecules and communicating between living cells and artificial cell models. Full article

A compact textile ultra-wideband (UWB) antenna with an electrical dimension of 0.24λ_o × 0.24λ_o × 0.009λ_o with microstrip line feed at lower edge and a frequency of operation of 2.96 GHz is proposed for UWB application. The analytical investigation using circuit theory concepts and the cavity model of the antenna is presented to validate the design. The main contribution of this paper is to propose a wearable antenna with wide impedance bandwidth of 118.68 % (2.96–11.6 GHz) applicable for UWB range of 3.1 to 10.6 GHz. The results present a maximum gain of 5.47 dBi at 7.3 GHz frequency. Moreover, this antenna exhibits Omni and quasi-Omni radiation patterns at various frequencies (4 GHz, 7 GHz and 10 GHz) for short-distance communication. The cutting notch and slot on the patch, and its effect on the antenna impedance to increase performance through current distribution is also presented. The time-domain characteristic of the proposed antenna is also discussed for the analysis of the pulse distortion phenomena. A constant group delay less than 1 ns is obtained over the entire operating impedance bandwidth (2.96–11.6 GHz) of the textile antenna in both situations, i.e., side by side and front to front. Linear phase consideration is also presented for both situations, as well as configurations of reception and transmission. An assessment of the effects of bending and humidity has been demonstrated by placing the antenna on the human body. The specific absorption rate (SAR) value was tested to show the radiation effect on the human body, and it was found that its impact on the human body SAR value is 1.68 W/kg, which indicates the safer limit to avoid radiation effects. Therefore, the proposed method is promising for telemedicine and mobile health systems. Full article

Surface structures with micro-grooves have been reported to be an effective way for improving the performance of metallic components. Through-mask electrochemical micromachining (TMEMM) is a promising process for fabricating micro-grooves. Due to the isotropic nature of metal dissolution, the dissolution of a workpiece occurs both along the width and depth. Overcut is generated inevitably with increasing depth, which makes it difficult to enhance machining localization. In this paper, a method of electrochemical machining using a conductive masked porous cathode and jet electrolyte supply is proposed to generate micro-grooves with high machining localization. In this configuration, the conductive mask is directly attached to the workpiece, thereby replacing the traditional insulated mask. This helps in achieving a reduction in overcut and an improvement in machining localization. Moreover, a metallic nozzle is introduced to supply a jetted electrolyte in the machining region with enhanced mass transfer via a porous cathode. The simulation and experimental results indicate that as compared with an insulated mask, the use of a conductive mask weakens the electric field intensity on both sides of machining region, which is helpful to reduce overcut and enhance machining localization. The effect of electrolyte pressure is investigated for this process configuration, and it has been observed that high electrolyte pressure enhances the mass transfer and improves the machining quality. In addition, as the pulse duty cycle is decreased, the dimensional standard deviation and roughness of the fabricated micro-groove are improved. The results suggest the feasibility and reliability of the proposed method. Full article

We demonstrate capture of event-related potentials (ERPs) using candle-like dry microneedle electrodes (CMEs). CMEs can record an electroencephalogram (EEG) even from hairy areas without any skin preparation, unlike conventional wet electrodes. In our previous research, we experimentally verified that CMEs can measure the spontaneous potential of EEG from the hairy occipital region without preparation with a signal-to-noise ratio as good as that of the conventional wet electrodes which require skin preparation. However, these results were based on frequency-based signals, which are relatively robust compared to noise contamination, and whether CMEs are sufficiently sensitive to capture finer signals remained unclear. Here, we first experimentally verified that CMEs can extract ERPs as good as conventional wet electrodes without preparation. In the auditory oddball tasks using pure tones, P300, which represent ERPs, was extracted with a signal-to-noise ratio as good as that of conventional wet electrodes. CMEs successfully captured perceptual activities. Then, we attempted to investigate cerebral cognitive activity using ERPs. In processing the vowel and prosody in auditory stimuli such as /itta/, /itte/, and /itta?/, laterality was observed that originated from the locations responsible for the process in near-infrared spectroscopy (NIRS) and magnetoencephalography experiments. We simultaneously measured ERPs with CMEs and NIRS in the oddball tasks using the three words. Laterality appeared in NIRS for six of 10 participants, although laterality was not clearly shown in the results, suggesting that EEGs have a limitation of poor spatial resolution. On the other hand, successful capturing of MMN and P300 using CMEs that do not require skin preparation may be readily applicable for real-time applications of human perceptual activities. Full article

In this paper, we present a comparative study of a cost-effective method for the mass fabrication of electrodes to be used in thin-film flexible supercapacitors. This technique is based on the laser-synthesis of graphene-based nanomaterials, specifically, laser-induced graphene and reduced graphene oxide. The synthesis of these materials was performed using two different lasers: a CO₂ laser with an infrared wavelength of λ = 10.6 µm and a UV laser (λ = 405 nm). After the optimization of the parameters of both lasers for this purpose, the performance of these materials as bare electrodes for flexible supercapacitors was studied in a comparative way. The experiments showed that the electrodes synthetized with the low-cost UV laser compete well in terms of specific capacitance with those obtained with the CO₂ laser, while the best performance is provided by the rGO electrodes fabricated with the CO₂ laser. It has also been demonstrated that the degree of reduction achieved with the UV laser for the rGO patterns was not enough to provide a good interaction electrode-electrolyte. Finally, we proved that the specific capacitance achieved with the presented supercapacitors can be improved by modifying the in-planar structure, without compromising their performance, which, together with their compatibility with doping-techniques and surface treatments processes, shows the potential of this technology for the fabrication of future high-performance and inexpensive flexible supercapacitors. Full article

The focus on novel systems for transdermal delivery of therapeutic agents has increased considerably over recent years, as this administration route comes with many advantages. Polymeric microarray patches (MAPs) are minimally invasive devices that enable systemic delivery of a wide range of drugs by overcoming the outer skin barrier. Conventionally, MAPs fabricated by micromoulding have a low needle density. In this study, the performance of hydrogel-forming MAPs cast using novel industrially manufactured micromoulds with a high needle density (600 needles/0.75 cm²) was compared to that of MAPs obtained using conventional moulds with a lower density (196 needles/0.89 cm²). Surrounding holders for micromoulds were designed for time-efficient fabrication of MAPs. The influence of needle densities on mechanical strength, insertion efficiency and in vitro permeation of ibuprofen sodium (IBU) was analysed. Insertion of both MAPs into an artificial skin model and neonatal porcine skin was comparable. No significant difference was observed in permeation studies of IBU (p > 0.05), with a delivery of 8.7 ± 1.7 mg for low-density and 9.5 ± 0.1 mg for high-density MAPs within 24 h. This highlights the potential of these novel micromoulds for manufacturing polymeric MAPs with a higher needle density for future applications. Full article

Airfoil selection procedure, wind tunnel testing and an implementation of 6-DOF model on flying wing micro aerial vehicle (FWMAV) has been proposed in this research. The selection procedure of airfoil has been developed by considering parameters related to aerodynamic efficiency and flight stability. Airfoil aerodynamic parameters have been calculated using a potential flow solver for ten candidate airfoils. Eppler-387 proved to be the most efficient reflexed airfoil and therefore was selected for fabrication and further flight testing of vehicle. Elevon control surfaces have been designed and evaluated for longitudinal and lateral control. The vehicle was fabricated using hot wire machine with EPP styrofoam of density 50 Kg/ ${\mathrm{m}}^3$ . Static aerodynamic coefficients were evaluated using wind tunnel tests conducted at cruise velocity of 20 m/s for varying angles of attack. Rate derivatives and elevon control derivatives have also been calculated. Equations of motion for FWMAV have been written in a body axis system yielding a 6-DOF model. It was found during flight tests that vehicle conducted coordinated turns with no appreciable adverse yaw. Since FWMAV was not designed with a vertical stabilizer and rudder control surface, directional stability was therefore augmented through winglets and high wing leading edge sweep. Major problems encountered during flight tests were related to left rolling tendency. The left roll tendency was found inherent to clockwise rotating propeller as ‘P’ factor, gyroscopic precession, torque effect and spiraling slipstream. To achieve successful flights, many actions were required including removal of excessive play from elevon control rods, active actuation of control surfaces, enhanced launch speed during take off, and increased throttle control during initial phase of flight. FWMAV flew many successful stable flights in which intended mission profile was accomplished, thereby validating the proposed airfoil selection procedure, modeling technique and proposed design. Full article

Endothelial cells sense and respond to shear stress. Different in vitro model systems have been used to study the cellular responses to shear stress, but these platforms do not allow studies on high numbers of cells under uniform and controllable shear stress. The annular dish, or dish-in-a-dish (DiaD), on the orbital shaker has been proposed as an accessible system to overcome these challenges. However, the influence of the DiaD design and the experimental parameters on the shear stress patterns is not known. In this study, we characterize different designs and experimental parameters (orbit size, speed and fluid height) using computational fluid dynamics. We optimize the DiaD for an atheroprotective flow, combining high shear stress levels with a low oscillatory shear index (OSI). We find that orbit size determines the DiaD design and parameters. The shear stress levels increase with increasing rotational speed and fluid height. Based on our optimization, we experimentally compare the 134/56 DiaD with regular dishes for cellular alignment and KLF2, eNOS, CDH2 and MCP1 expression. The calculated OSI has a strong impact on alignment and gene expression, emphasizing the importance of characterizing shear profiles in orbital setups. Full article