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Micromachines, Volume 9, Issue 3 (March 2018) – 47 articles

Cover Story (view full-size image): Circulating tumor cells (CTCs) are regarded as a strong biomarker which includes clinically valuable information. However, CTCs are very rare and require precise separation and detection for effective clinical applications. In this paper, we report a flow-restricted microfluidic trap array capable of deterministic single-cell capture of CTCs. The single-CTC capturing ability not only showed cell enumerating ability but also high prospects for application in future automated downstream analysis. View this paper
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9 pages, 1236 KiB  
Article
Fabrication of Through via Holes in Ultra-Thin Fused Silica Wafers for Microwave and Millimeter-Wave Applications
by Xiao Li, King Yuk Chan and Rodica Ramer
Micromachines 2018, 9(3), 138; https://doi.org/10.3390/mi9030138 - 20 Mar 2018
Cited by 5 | Viewed by 4793
Abstract
Through via holes in fused silica are a key infrastructure element of microwave and millimeter-wave circuits and 3D integration. In this work, etching through via holes in ultra-thin fused silica wafers using deep reactive-ion etching (DRIE) and laser ablation was developed and analyzed. [...] Read more.
Through via holes in fused silica are a key infrastructure element of microwave and millimeter-wave circuits and 3D integration. In this work, etching through via holes in ultra-thin fused silica wafers using deep reactive-ion etching (DRIE) and laser ablation was developed and analyzed. The experimental setup and process parameters for both methods are presented and compared. For DRIE, three types of mask materials including KMPR 1035 (Nippon Kayaku, Tokyo, Japan) photoresist, amorphous silicon and chromium—with their corresponding optimized processing recipes—were tested, aiming at etching through a 100 μm fused silica wafer. From the experiments, we concluded that using chromium as the masking material is the best choice when using DRIE. However, we found that the laser ablation method with a laser pulse fluence of 2.89 J/cm2 and a pulse overlap of 91% has advantages over DRIE. The laser ablation method has a simpler process complexity, while offering a fair etching result. In particular, the sidewall profile angle is measured to be 75° to the bottom surface of the wafer, which is ideal for the subsequent metallization process. As a demonstration, a two-inch wafer with 624 via holes was processed using both technologies, and the laser ablation method showed better efficiency compared to DRIE. Full article
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15 pages, 4089 KiB  
Article
Topology Optimization of Passive Micromixers Based on Lagrangian Mapping Method
by Yuchen Guo, Yifan Xu, Yongbo Deng and Zhenyu Liu
Micromachines 2018, 9(3), 137; https://doi.org/10.3390/mi9030137 - 20 Mar 2018
Cited by 13 | Viewed by 3877
Abstract
This paper presents an optimization-based design method of passive micromixers for immiscible fluids, which means that the Peclet number infinitely large. Based on topology optimization method, an optimization model is constructed to find the optimal layout of the passive micromixers. Being different from [...] Read more.
This paper presents an optimization-based design method of passive micromixers for immiscible fluids, which means that the Peclet number infinitely large. Based on topology optimization method, an optimization model is constructed to find the optimal layout of the passive micromixers. Being different from the topology optimization methods with Eulerian description of the convection-diffusion dynamics, this proposed method considers the extreme case, where the mixing is dominated completely by the convection with negligible diffusion. In this method, the mixing dynamics is modeled by the mapping method, a Lagrangian description that can deal with the case with convection-dominance. Several numerical examples have been presented to demonstrate the validity of the proposed method. Full article
(This article belongs to the Special Issue Passive Micromixers)
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10 pages, 5243 KiB  
Review
Optofluidics Refractometers
by Cheng Li, Gang Bai, Yunxiao Zhang, Min Zhang and Aoqun Jian
Micromachines 2018, 9(3), 136; https://doi.org/10.3390/mi9030136 - 20 Mar 2018
Cited by 22 | Viewed by 5222
Abstract
Refractometry is a classic analytical method in analytical chemistry and biosensing. By integrating advanced micro- and nano-optical systems with well-developed microfluidics technology, optofluidics are shown to be a powerful, smart and universal platform for refractive index sensing applications. This paper reviews recent work [...] Read more.
Refractometry is a classic analytical method in analytical chemistry and biosensing. By integrating advanced micro- and nano-optical systems with well-developed microfluidics technology, optofluidics are shown to be a powerful, smart and universal platform for refractive index sensing applications. This paper reviews recent work on optofluidic refractometers based on different sensing mechanisms and structures (e.g., photonic crystal/photonic crystal fibers, waveguides, whisper gallery modes and surface plasmon resonance), and traces the performance enhancement due to the synergistic integration of optics and microfluidics. A brief discussion of future trends in optofluidic refractometers, namely volume sensing and resolution enhancement, are also offered. Full article
(This article belongs to the Special Issue Advances in Optofluidics)
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11 pages, 4484 KiB  
Article
Dielectrophoretic Microfluidic Device for in Vitro Fertilization
by Hong-Yuan Huang, Yun-Li Lai and Da-Jeng Yao
Micromachines 2018, 9(3), 135; https://doi.org/10.3390/mi9030135 - 20 Mar 2018
Cited by 14 | Viewed by 5152
Abstract
The aim of this work was to create a microfluidic platform that uses in vitro fertilization (IVF) and avoids unnecessary damage to oocytes due to the dielectrophoretic force manipulation of the sperms and oocytes that occurs in a traditional IVF operation. The device [...] Read more.
The aim of this work was to create a microfluidic platform that uses in vitro fertilization (IVF) and avoids unnecessary damage to oocytes due to the dielectrophoretic force manipulation of the sperms and oocytes that occurs in a traditional IVF operation. The device from this research can serve also to decrease medium volumes, as well as the cost of cell culture under evaporation, and to prevent unnecessary risk in intracytoplasmic sperm injection (ICSI). To decrease the impact and destruction of the oocyte and the sperm, we adopted a positive dielectrophoretic force to manipulate both the sperms and the oocyte. The mouse oocytes were trapped with a positive dielectrophoretic (p-DEP) force by using Indium Tin Oxide (ITO)-glass electrodes; the ITO-glass electrode chip was fabricated by wet etching the ITO-glass. The polydimethylsiloxane (PDMS) flow-focusing microfluidic device was used to generate microdroplets of micrometer size to contain the zygotes. The volume of the microdroplets was controlled by adjusting the flow rates of both inlets for oil and the DEP buffer. As a result, the rate of fertilization was increased by about 5% beyond that of the DEP treatment in traditional IVF, and more than 20% developed to the blastocyst stage with a low sperm-oocyte ratio. Full article
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13 pages, 3314 KiB  
Article
Modeling and Analysis of an Opto-Fluidic Sensor for Lab-on-a-Chip Applications
by Venkatesha Muniswamy, Chaya Bangalore Muniraju, Prasant Kumar Pattnaik and Narayan Krishnaswamy
Micromachines 2018, 9(3), 134; https://doi.org/10.3390/mi9030134 - 19 Mar 2018
Cited by 5 | Viewed by 4057
Abstract
In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of microparticles in the microfluidic channel for lab-on-a-chip (LOC) sensing application is presented. This sensor consists of integrated optical [...] Read more.
In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of microparticles in the microfluidic channel for lab-on-a-chip (LOC) sensing application is presented. This sensor consists of integrated optical waveguides, microfluidic channel among other integrated optical components. A continuous flow of microparticles in a narrow fluidic channel is achieved by maintaining the two sealed chambers at different temperatures and by maintaining a constant pressure of 1 Pa at the centroid of narrow fluidic channel geometry. The analysis of silicon on insulator (SOI) integrated optical waveguide at an infrared wavelength of 1550 nm for single mode sensing operation is presented. The optical loss is found to be 5.7 × 10−4 dB/cm with an effective index of 2.3. The model presented in this work can be effectively used to detect the nature of microparticles and continuous monitoring of pathological parameters for sensing applications. Full article
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9 pages, 3153 KiB  
Article
Fabrication and Study of Micro Monolithic Tungsten Ball Tips for Micro/Nano-CMM Probes
by Ruijun Li, Chen Chen, Kuangchao Fan, Zhiwei Wang, Fangfang Liu and Qiangxian Huang
Micromachines 2018, 9(3), 133; https://doi.org/10.3390/mi9030133 - 19 Mar 2018
Cited by 7 | Viewed by 3808
Abstract
Micro ball tips with high precision, small diameter, and high stiffness stems are required to measure microstructures with high aspect ratio. Existing ball tips cannot meet such demands because of their weak qualities. This study used an arc-discharge melting method to fabricate a [...] Read more.
Micro ball tips with high precision, small diameter, and high stiffness stems are required to measure microstructures with high aspect ratio. Existing ball tips cannot meet such demands because of their weak qualities. This study used an arc-discharge melting method to fabricate a micro monolithic tungsten ball tip on a tungsten stylus. The principles of arc discharge and surface tension phenomenon were introduced. The experimental setup was designed and established. Appropriate process parameters, such as impulse voltage, electro discharge time, and discharge gap were determined. Experimental results showed that a ball tip of approximately 60 µm in diameter with less than 0.6 µm roundness error and 0.6 µm center offset could be realized on a 100 µm-diameter tungsten wire. The fabricated micro ball tip was installed on a homemade probe, touched by high-precision gauge blocks in different directions. A repeatability of 41 nm (K = 2) was obtained. Several interesting phenomena in the ball-forming process were also discussed. The proposed method could be used to fabricate a monolithic probe ball tip, which is necessary for measuring microstructures. Full article
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10 pages, 4891 KiB  
Article
Single-Wall Carbon Nanotube-Coated Cotton Yarn for Electrocardiography Transmission
by Yuliang Zhao, Yuying Cao, Junshan Liu, Zhikun Zhan, Xiaoli Li and Wen Jung Li
Micromachines 2018, 9(3), 132; https://doi.org/10.3390/mi9030132 - 19 Mar 2018
Cited by 22 | Viewed by 6059
Abstract
We fabricated a type of conductive fabric, specifically single-wall carbon nanotube-coated cotton yarns (SWNT-CYs), for electrocardiography (ECG) signal transmission utilizing a “dipping and drying” method. The conductive cotton yarns were prepared by dipping cotton yarns in SWNTs (single-wall carbon nanotubes) solutions and then [...] Read more.
We fabricated a type of conductive fabric, specifically single-wall carbon nanotube-coated cotton yarns (SWNT-CYs), for electrocardiography (ECG) signal transmission utilizing a “dipping and drying” method. The conductive cotton yarns were prepared by dipping cotton yarns in SWNTs (single-wall carbon nanotubes) solutions and then drying them at room temperature—a simple process that shows consistency in successfully coating cotton yarns with conductive carbon nanotubes (CNTs). The influence of fabrication conditions on the conductivity properties of SWNT-CYs was investigated. The results demonstrate that our conductive yarns can transmit weak bio-electrical (i.e., ECG) signals without significant attenuation and distortion. Our conductive cotton yarns, which combine the flexibility of conventional fabrics and the good conductivity of SWNTs, are promising materials for wearable electronics and sensor applications in the future. Full article
(This article belongs to the Special Issue Carbon Based Materials for MEMS/NEMS)
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14 pages, 3095 KiB  
Article
Silicon-Based Microfabrication of Free-Floating Neural Probes and Insertion Tool for Chronic Applications
by Andreas Schander, Heiko Stemmann, Andreas K. Kreiter and Walter Lang
Micromachines 2018, 9(3), 131; https://doi.org/10.3390/mi9030131 - 16 Mar 2018
Cited by 13 | Viewed by 6654
Abstract
Bidirectional neural interfaces for multi-channel, high-density recording and electrical stimulation of neural activity in the central nervous system are fundamental tools for neuroscience and medical applications. Especially for clinical use, these electrical interfaces must be stable over several years, which is still a [...] Read more.
Bidirectional neural interfaces for multi-channel, high-density recording and electrical stimulation of neural activity in the central nervous system are fundamental tools for neuroscience and medical applications. Especially for clinical use, these electrical interfaces must be stable over several years, which is still a major challenge due to the foreign body response of neural tissue. A feasible solution to reduce this inflammatory response is to enable a free-floating implantation of high-density, silicon-based neural probes to avoid mechanical coupling between the skull and the cortex during brain micromotion. This paper presents our latest development of a reproducible microfabrication process, which allows a monolithic integration of a highly-flexible, polyimide-based cable with a silicon-stiffened neural probe at a high resolution of 1 µm. For a precise and complete insertion of the free-floating probes into the cortex, a new silicon-based, vacuum-actuated insertion tool is presented, which can be attached to commercially available electrode drives. To reduce the electrode impedance and enable safe and stable microstimulation an additional coating with the electrical conductive polymer PEDOT:PSS is used. The long-term stability of the presented free-floating neural probes is demonstrated in vitro and in vivo. The promising results suggest the feasibility of these neural probes for chronic applications. Full article
(This article belongs to the Special Issue Silicon-based Micro/Nanofabrication for Biomedical Applications)
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12 pages, 17887 KiB  
Article
Crack-Configuration Analysis of Metal Conductive Track Embedded in Stretchable Elastomer
by Tomoya Koshi and Eiji Iwase
Micromachines 2018, 9(3), 130; https://doi.org/10.3390/mi9030130 - 15 Mar 2018
Cited by 5 | Viewed by 6447
Abstract
This paper reports the analysis of the crack configuration of a stretched metal conductive track that is embedded in a stretchable elastomer. The factor determining the crack configurations is analyzed by modeling as well as experiments. The modeling analysis indicates that the crack [...] Read more.
This paper reports the analysis of the crack configuration of a stretched metal conductive track that is embedded in a stretchable elastomer. The factor determining the crack configurations is analyzed by modeling as well as experiments. The modeling analysis indicates that the crack configuration is determined by the ratio of the elongation stiffness of the track and elastomer, and is classified into two types: multiple-crack growth and single-crack growth. When the track stiffness is considerably lower than the elastomer stiffness, multiple-crack growth type occurs; in the opposite case, single-crack growth type occurs. Hence, to verify the modeling analysis, metal conductive tracks with different thicknesses are fabricated, and the cracks are studied with respect to the crack width, number of cracks, and crack propagation speed. In this study, two conventional metal-track shapes are studied: straight-shaped tracks with track thickness of 0.04–1.17 µm, and wave-shaped tracks with track thickness of 2–10 µm. For straight-shaped tracks, multiple-crack growth type occurred, when the track thickness was 0.04 µm, and the crack configuration gradually changed to a single crack, with the increase in the track thickness. For wave-shaped tracks with track thickness of 2–10 µm, only single-crack growth type occurred; however, the crack propagation speed decreased and the maximum stretchability of the track increased, with the increase in the track thickness. Full article
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15 pages, 2765 KiB  
Article
A Label Free Disposable Device for Rapid Isolation of Rare Tumor Cells from Blood by Ultrasounds
by Itziar González, Julie Earl, Luis J. Fernández, Bruno Sainz, Alberto Pinto, Rosa Monge, Sonia Alcalá, Adela Castillejo, Jose L. Soto and Alfredo Carrato
Micromachines 2018, 9(3), 129; https://doi.org/10.3390/mi9030129 - 15 Mar 2018
Cited by 16 | Viewed by 4210
Abstract
The use of blood samples as liquid biopsy is a label-free method for cancer diagnosis that offers benefits over traditional invasive biopsy techniques. Cell sorting by acoustic waves offers a means to separate rare cells from blood samples based on their physical properties [...] Read more.
The use of blood samples as liquid biopsy is a label-free method for cancer diagnosis that offers benefits over traditional invasive biopsy techniques. Cell sorting by acoustic waves offers a means to separate rare cells from blood samples based on their physical properties in a label-free, contactless and biocompatible manner. Herein, we describe a flow-through separation approach that provides an efficient separation of tumor cells (TCs) from white blood cells (WBCs) in a microfluidic device, “THINUS-Chip” (Thin-Ultrasonic-Separator-Chip), actuated by ultrasounds. We introduce for the first time the concept of plate acoustic waves (PAW) applied to acoustophoresis as a new strategy. It lies in the geometrical chip design: different to other microseparators based on either bulk acoustic waves (BAW) or surface waves (SAW, SSAW and tSAW), it allows the use of polymeric materials without restrictions in the frequency of work. We demonstrate its ability to perform high-throughput isolation of TCs from WBCs, allowing a recovery rate of 84% ± 8% of TCs with a purity higher than 80% and combined viability of 85% at a flow rate of 80 μL/min (4.8 mL/h). The THINUS-Chip performs cell fractionation with low-cost manufacturing processes, opening the door to possible easy printing fabrication. Full article
(This article belongs to the Special Issue Microfluidics for Circulating Biomarkers)
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8 pages, 2082 KiB  
Article
Method of Measuring the Mismatch of Parasitic Capacitance in MEMS Accelerometer Based on Regulating Electrostatic Stiffness
by Xianshan Dong, Shaohua Yang, Junhua Zhu, Yunfei En and Qinwen Huang
Micromachines 2018, 9(3), 128; https://doi.org/10.3390/mi9030128 - 15 Mar 2018
Cited by 14 | Viewed by 4202
Abstract
For the MEMS capacitive accelerometer, parasitic capacitance is a serious problem. Its mismatch will deteriorate the performance of accelerometer. Obtaining the mismatch of the parasitic capacitance precisely is helpful for improving the performance of bias and scale. Currently, the method of measuring the [...] Read more.
For the MEMS capacitive accelerometer, parasitic capacitance is a serious problem. Its mismatch will deteriorate the performance of accelerometer. Obtaining the mismatch of the parasitic capacitance precisely is helpful for improving the performance of bias and scale. Currently, the method of measuring the mismatch is limited in the direct measuring using the instrument. This traditional method has low accuracy for it would lead in extra parasitic capacitive and have other problems. This paper presents a novel method based on the mechanism of a closed-loop accelerometer. The strongly linear relationship between the output of electric force and the square of pre-load voltage is obtained through theoretical derivation and validated by experiment. Based on this relationship, the mismatch of parasitic capacitance can be obtained precisely through regulating electrostatic stiffness without other equipment. The results can be applied in the design of decreasing the mismatch and electrical adjusting for eliminating the influence of the mismatch. Full article
(This article belongs to the Special Issue MEMS Accelerometers)
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16 pages, 8399 KiB  
Article
Experimental Investigation on Ductile Mode Micro-Milling of ZrO2 Ceramics with Diamond-Coated End Mills
by Rong Bian, Eleonora Ferraris, Yinfei Ynag and Jun Qian
Micromachines 2018, 9(3), 127; https://doi.org/10.3390/mi9030127 - 14 Mar 2018
Cited by 23 | Viewed by 5576
Abstract
ZrO2 ceramics are currently used in a broad range of industrial applications. However, the machining of post-sintered ZrO2 ceramic is a difficult task, due to its high hardness and brittleness. In this study, micro-milling of ZrO2 with two kinds of [...] Read more.
ZrO2 ceramics are currently used in a broad range of industrial applications. However, the machining of post-sintered ZrO2 ceramic is a difficult task, due to its high hardness and brittleness. In this study, micro-milling of ZrO2 with two kinds of diamond-coated end mills has been conducted on a Kern MMP 2522 micro-milling center (Kern Microtechnik GmbH, Eschenlohe, Germany). To achieve a ductile mode machining of ZrO2, the feed per tooth and depth of cut was set in the range of a few micrometers. Cutting force and machined surface roughness have been measured by a Kistler MiniDynamometer (Kistler Group, Winterthur, Switzerland) and a Talysurf 120 L profilometer (Taylor Hobson Ltd., Leicester, UK), respectively. Machined surface topography and tool wear have been examined under SEM. Experiment results show that the material can be removed in ductile mode, and mirror quality surface with Ra low as 0.02 μm can be achieved. Curled and smooth chips have been collected and observed. The axial cutting force Fz is always bigger than Fx and Fy, and presents a rising trend with increasing of milling length. Tool wear includes delamination of diamond coating and wear of tungsten carbide substrate. Without the protection of diamond coating, the tungsten carbide substrate was worn out quickly, resulting a change of tool tip geometry. Full article
(This article belongs to the Special Issue Micro-Machining: Challenges and Opportunities)
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19 pages, 7304 KiB  
Article
Micro-UFO (Untethered Floating Object): A Highly Accurate Microrobot Manipulation Technique
by Hüseyin Uvet, Ali Anil Demircali, Yusuf Kahraman, Rahmetullah Varol, Tunc Kose and Kadir Erkan
Micromachines 2018, 9(3), 126; https://doi.org/10.3390/mi9030126 - 14 Mar 2018
Cited by 20 | Viewed by 8301
Abstract
A new microrobot manipulation technique with high precision (nano level) positional accuracy to move in a liquid environment with diamagnetic levitation is presented. Untethered manipulation of microrobots by means of externally applied magnetic forces has been emerging as a promising field of research, [...] Read more.
A new microrobot manipulation technique with high precision (nano level) positional accuracy to move in a liquid environment with diamagnetic levitation is presented. Untethered manipulation of microrobots by means of externally applied magnetic forces has been emerging as a promising field of research, particularly due to its potential for medical and biological applications. The purpose of the presented method is to eliminate friction force between the surface of the substrate and microrobot. In an effort to achieve high accuracy motion, required magnetic force for the levitation of the microrobot was determined by finite element method (FEM) simulations in COMSOL (version 5.3, COMSOL Inc., Stockholm, Sweden) and verified by experimental results. According to position of the lifter magnet, the levitation height of the microrobot in the liquid was found analytically, and compared with the experimental results head-to-head. The stable working range of the microrobot is between 30 µm to 330 µm, and it was confirmed in both simulations and experimental results. It can follow the given trajectory with high accuracy (<1 µm error avg.) at varied speeds and levitation heights. Due to the nano-level positioning accuracy, desired locomotion can be achieved in pre-specified trajectories (sinusoidal or circular). During its locomotion, phase difference between lifter magnet and carrier magnet has been observed, and relation with drag force effect has been discussed. Without using strong electromagnets or bulky permanent magnets, our manipulation approach can move the microrobot in three dimensions in a liquid environment. Full article
(This article belongs to the Special Issue Micro/Nano Robotics, Volume II)
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10 pages, 1949 KiB  
Communication
Digital Manufacturing of Selective Porous Barriers in Microchannels Using Multi-Material Stereolithography
by Yong Tae Kim, Kurt Castro, Nirveek Bhattacharjee and Albert Folch
Micromachines 2018, 9(3), 125; https://doi.org/10.3390/mi9030125 - 14 Mar 2018
Cited by 36 | Viewed by 6706
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue 3D Printed Microfluidic Devices)
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12 pages, 13384 KiB  
Article
Microstructure Formation of Functional Polymers by Evaporative Self-Assembly under Flexible Geometric Confinement
by Xiangmeng Li, Xijing Zhu and Huifen Wei
Micromachines 2018, 9(3), 124; https://doi.org/10.3390/mi9030124 - 12 Mar 2018
Cited by 3 | Viewed by 4815
Abstract
Polymer microstructures are widely used in optics, flexible electronics, and so forth. We demonstrate a cost-effective bottom-up manner for patterning polymer microstructures by evaporative self-assembly under a flexible geometric confinement at a high temperature. Two-parallel-plates confinement would become curve-to-flat shape geometric confinement as [...] Read more.
Polymer microstructures are widely used in optics, flexible electronics, and so forth. We demonstrate a cost-effective bottom-up manner for patterning polymer microstructures by evaporative self-assembly under a flexible geometric confinement at a high temperature. Two-parallel-plates confinement would become curve-to-flat shape geometric confinement as the polydimethylsiloxane (PDMS) cover plate deformed during solvent swelling. We found that a flexible cover plate would be favorable for the formation of gradient microstructures, with various periodicities and widths obtained at varied heights of clearance. After thermal annealing, the edge of the PMMA (Poly-methylmethacrylate) microstructures would become smooth, while the RR-P3HT (regioregular-poly(3-hexylthiophene)) might generate nanocrystals. The morphologies of RR-P3HT structures included thick films, straight lines, hierarchical stripes, incomplete stripes, and regular dots. Finally, a simple field-effect transistor (FET) device was demonstrated with the RR-P3HT micropattern as an active layer. Full article
(This article belongs to the Special Issue Self-Assembly of Polymers)
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14 pages, 2301 KiB  
Article
Three-Dimensional Reservoir-Based Dielectrophoresis (rDEP) for Enhanced Particle Enrichment
by Akshay Kale, Saurin Patel and Xiangchun Xuan
Micromachines 2018, 9(3), 123; https://doi.org/10.3390/mi9030123 - 10 Mar 2018
Cited by 23 | Viewed by 4789
Abstract
Selective enrichment of target species is crucial for a wide variety of engineering systems for improved performance of subsequent processes. Dielectrophoresis (DEP) is a powerful electrokinetic method that can be used to focus, trap, concentrate, and separate a variety of species in a [...] Read more.
Selective enrichment of target species is crucial for a wide variety of engineering systems for improved performance of subsequent processes. Dielectrophoresis (DEP) is a powerful electrokinetic method that can be used to focus, trap, concentrate, and separate a variety of species in a label-free manner. The commonly employed methods for DEP suffer from limitations such as electrode fouling and high susceptibility to Joule heating effects. Recently, our group has demonstrated DEP-based manipulations of particles and cells using a novel method of reservoir-based dielectrophoresis (rDEP) which exploits the naturally produced electric field gradients at the reservoir-microchannel junction. Although this method reasonably addresses the limitations mentioned above while maintaining a high simplicity of fabrication, all of our demonstrations so far have used a two-dimensional rDEP, which limits the performance of the devices. This work aims to improve their performance further by making the DEP three-dimensional. Through detailed experimental and numerical analysis, we demonstrate a six-fold increase in the enrichment performance of latex beads and a significant reduction in the power consumption for the new devices, which would allow a more reliable integration of the same into micro-total analysis systems. Full article
(This article belongs to the Special Issue Micro/Nano-Chip Electrokinetics, Volume II)
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14 pages, 3782 KiB  
Review
Advances of Optofluidic Microcavities for Microlasers and Biosensors
by Zhiqing Feng and Lan Bai
Micromachines 2018, 9(3), 122; https://doi.org/10.3390/mi9030122 - 09 Mar 2018
Cited by 12 | Viewed by 6263
Abstract
Optofluidic microcavities with high Q factor have made rapid progress in recent years by using various micro-structures. On one hand, they are applied to microfluidic lasers with low excitation thresholds. On the other hand, they inspire the innovation of new biosensing devices with [...] Read more.
Optofluidic microcavities with high Q factor have made rapid progress in recent years by using various micro-structures. On one hand, they are applied to microfluidic lasers with low excitation thresholds. On the other hand, they inspire the innovation of new biosensing devices with excellent performance. In this article, the recent advances in the microlaser research and the biochemical sensing field will be reviewed. The former will be categorized based on the structures of optical resonant cavities such as the Fabry–Pérot cavity and whispering gallery mode, and the latter will be classified based on the working principles into active sensors and passive sensors. Moreover, the difficulty of single-chip integration and recent endeavors will be briefly discussed. Full article
(This article belongs to the Special Issue Advances in Optofluidics)
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18 pages, 3603 KiB  
Article
A Novel High-Precision Digital Tunneling Magnetic Resistance-Type Sensor for the Nanosatellites’ Space Application
by Xiangyu Li, Jianping Hu, Weiping Chen, Liang Yin and Xiaowei Liu
Micromachines 2018, 9(3), 121; https://doi.org/10.3390/mi9030121 - 09 Mar 2018
Cited by 22 | Viewed by 7330
Abstract
Micro-electromechanical system (MEMS) magnetic sensors are widely used in the nanosatellites field. We proposed a novel high-precision miniaturized three-axis digital tunneling magnetic resistance-type (TMR) sensor. The design of the three-axis digital magnetic sensor includes a low-noise sensitive element and high-performance interface circuit. The [...] Read more.
Micro-electromechanical system (MEMS) magnetic sensors are widely used in the nanosatellites field. We proposed a novel high-precision miniaturized three-axis digital tunneling magnetic resistance-type (TMR) sensor. The design of the three-axis digital magnetic sensor includes a low-noise sensitive element and high-performance interface circuit. The TMR sensor element can achieve a background noise of 150 pT/Hz1/2 by the vertical modulation film at a modulation frequency of 5 kHz. The interface circuit is mainly composed of an analog front-end current feedback instrumentation amplifier (CFIA) with chopper structure and a fully differential 4th-order Sigma-Delta (ΣΔ) analog to digital converter (ADC). The low-frequency 1/f noise of the TMR magnetic sensor are reduced by the input-stage and system-stage chopper. The dynamic element matching (DEM) is applied to average out the mismatch between the input and feedback transconductor so as to improve the gain accuracy and gain drift. The digital output is achieved by a switched-capacitor ΣΔ ADC. The interface circuit is implemented by a 0.35 μm CMOS technology. The performance test of the TMR magnetic sensor system shows that: at a 5 V operating voltage, the sensor can achieve a power consumption of 120 mW, a full scale of ±1 Guass, a bias error of 0.01% full scale (FS), a nonlinearity of x-axis 0.13% FS, y-axis 0.11% FS, z-axis 0.15% FS and a noise density of x-axis 250 pT/Hz1/2 (at 1 Hz), y-axis 240 pT/Hz1/2 (at 1 Hz), z-axis 250 pT/Hz1/2 (at 1 Hz), respectively. This work has a less power consumption, a smaller size, and higher resolution than other miniaturized magnetometers by comparison. Full article
(This article belongs to the Special Issue Development of CMOS-MEMS/NEMS Devices)
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15 pages, 15992 KiB  
Article
Design, Fabrication, and Performance Characterization of LTCC-Based Capacitive Accelerometers
by Huan Liu, Runiu Fang, Min Miao, Yichuan Zhang, Yingzhan Yan, Xiaoping Tang, Huixiang Lu and Yufeng Jin
Micromachines 2018, 9(3), 120; https://doi.org/10.3390/mi9030120 - 09 Mar 2018
Cited by 11 | Viewed by 6057
Abstract
In this paper, two versions of capacitive accelerometers based on low-temperature co-fired ceramic (LTCC) technology are developed, different with respect to the detection technique, as well as the mechanical structure. Fabrication of the key structure, a heavy proof mass with thin beams embedded [...] Read more.
In this paper, two versions of capacitive accelerometers based on low-temperature co-fired ceramic (LTCC) technology are developed, different with respect to the detection technique, as well as the mechanical structure. Fabrication of the key structure, a heavy proof mass with thin beams embedded in a large cavity, which is extremely difficult for the conventional LTCC process, is successfully completed by the optimized process. The LC resonant accelerometer, using coupling resonance frequency sensing which is first applied to LTCC accelerometer and may facilitate application in harsh environments, demonstrates a sensitivity of 375 KHz/g over the full scale range 1 g, with nonlinearity less than 6%, and the telemetry distance is 5 mm. The differential capacitive accelerometer adopting differential capacitive sensing presents a larger full scale range 10 g and lower nonlinearity less than 1%, and the sensitivity is 30.27 mV/g. Full article
(This article belongs to the Special Issue MEMS Accelerometers)
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18 pages, 4328 KiB  
Article
Study of the Operational Safety of a Vascular Interventional Surgical Robotic System
by Jian Guo, Xiaoliang Jin and Shuxiang Guo
Micromachines 2018, 9(3), 119; https://doi.org/10.3390/mi9030119 - 08 Mar 2018
Cited by 52 | Viewed by 5456
Abstract
This paper proposes an operation safety early warning system based on LabView (2014, National Instruments Corporation, Austin, TX, USA) for vascular interventional surgery (VIS) robotic system. The system not only provides intuitive visual feedback information for the surgeon, but also has a safety [...] Read more.
This paper proposes an operation safety early warning system based on LabView (2014, National Instruments Corporation, Austin, TX, USA) for vascular interventional surgery (VIS) robotic system. The system not only provides intuitive visual feedback information for the surgeon, but also has a safety early warning function. It is well known that blood vessels differ in their ability to withstand stress in different age groups, therefore, the operation safety early warning system based on LabView has a vascular safety threshold function that changes in real-time, which can be oriented to different age groups of patients and a broader applicable scope. In addition, the tracing performance of the slave manipulator to the master manipulator is also an important index for operation safety. Therefore, we also transformed the slave manipulator and integrated the displacement error compensation algorithm in order to improve the tracking ability of the slave manipulator to the master manipulator and reduce master–slave tracking errors. We performed experiments “in vitro” to validate the proposed system. According to previous studies, 0.12 N is the maximum force when the blood vessel wall has been penetrated. Experimental results showed that the proposed operation safety early warning system based on LabView combined with operating force feedback can effectively avoid excessive collisions between the surgical catheter and vessel wall to avoid vascular puncture. The force feedback error of the proposed system is maintained between ±20 mN, which is within the allowable safety range and meets our design requirements. Therefore, the proposed system can ensure the safety of surgery. Full article
(This article belongs to the Special Issue Biomedical Microdevices: Design, Fabrication and Application)
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15 pages, 10005 KiB  
Article
Determination of the Three-Dimensional Rate of Cancer Cell Rotation in an Optically-Induced Electrokinetics Chip Using an Optical Flow Algorithm
by Yuliang Zhao, Dayu Jia, Xiaopeng Sha, Guanglie Zhang and Wen Jung Li
Micromachines 2018, 9(3), 118; https://doi.org/10.3390/mi9030118 - 08 Mar 2018
Cited by 10 | Viewed by 4148
Abstract
Our group has reported that Melan-A cells and lymphocytes undergo self-rotation in a homogeneous AC electric field, and found that the rotation velocity of these cells is a key indicator to characterize their physical properties. However, the determination of the rotation properties of [...] Read more.
Our group has reported that Melan-A cells and lymphocytes undergo self-rotation in a homogeneous AC electric field, and found that the rotation velocity of these cells is a key indicator to characterize their physical properties. However, the determination of the rotation properties of a cell by human eyes is both gruesome and time consuming, and not always accurate. In this paper, a method is presented to more accurately determine the 3D cell rotation velocity and axis from a 2D image sequence captured by a single camera. Using the optical flow method, we obtained the 2D motion field data from the image sequence and back-project it onto a 3D sphere model, and then the rotation axis and velocity of the cell were calculated. After testing the algorithm on animated image sequences, experiments were also performed on image sequences of real rotating cells. All of these results indicate that this method is accurate, practical, and useful. Furthermore, the method presented there can also be used to determine the 3D rotation velocity of other types of spherical objects that are commonly used in microfluidic applications, such as beads and microparticles. Full article
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8 pages, 2175 KiB  
Article
Monitoring of Non-Ferrous Wear Debris in Hydraulic Oil by Detecting the Equivalent Resistance of Inductive Sensors
by Lin Zeng, Hongpeng Zhang, Qiang Wang and Xingming Zhang
Micromachines 2018, 9(3), 117; https://doi.org/10.3390/mi9030117 - 08 Mar 2018
Cited by 28 | Viewed by 4211
Abstract
Wear debris in hydraulic oil contains important information on the operation of equipment, which is important for condition monitoring and fault diagnosis in mechanical equipment. A micro inductive sensor based on the inductive coulter principle is presented in this work. It consists of [...] Read more.
Wear debris in hydraulic oil contains important information on the operation of equipment, which is important for condition monitoring and fault diagnosis in mechanical equipment. A micro inductive sensor based on the inductive coulter principle is presented in this work. It consists of a straight micro-channel and a 3-D solenoid coil wound on the micro-channel. Instead of detecting the inductance change of the inductive sensor, the equivalent resistance change of the inductive sensor is detected for non-ferrous particle (copper particle) monitoring. The simulation results show that the resistance change rate caused by the presence of copper particles is greater than the inductance change rate. Copper particles with sizes ranging from 48 μm to 150 μm were used in the experiment, and the experimental results are in good agreement with the simulation results. By detecting the inductive change of the micro inductive sensor, the detection limit of the copper particles only reaches 70 μm. However, the detection limit can be improved to 48 μm by detecting the equivalent resistance of the inductive sensor. The equivalent resistance method was demonstrated to have a higher detection accuracy than conventional inductive detection methods for non-ferrous particle detection in hydraulic oil. Full article
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11 pages, 15810 KiB  
Technical Note
Characterization of 3D-Printed Moulds for Soft Lithography of Millifluidic Devices
by Nurul Mohd Fuad, Megan Carve, Jan Kaslin and Donald Wlodkowic
Micromachines 2018, 9(3), 116; https://doi.org/10.3390/mi9030116 - 08 Mar 2018
Cited by 25 | Viewed by 7770
Abstract
Increased demand for inexpensive and rapid prototyping methods for micro- and millifluidic lab-on-a-chip (LOC) devices has stimulated considerable interest in alternative cost-effective fabrication techniques. Additive manufacturing (AM)—also called three-dimensional (3D) printing—provides an attractive alternative to conventional fabrication techniques. AM has been used to [...] Read more.
Increased demand for inexpensive and rapid prototyping methods for micro- and millifluidic lab-on-a-chip (LOC) devices has stimulated considerable interest in alternative cost-effective fabrication techniques. Additive manufacturing (AM)—also called three-dimensional (3D) printing—provides an attractive alternative to conventional fabrication techniques. AM has been used to produce LOC master moulds from which positive replicas are made using soft-lithography and a biocompatible elastomer, poly(dimethylsiloxane) (PDMS). Here we characterize moulds made using two AM methods—stereolithography (SLA) and material-jetting (MJ)—and the positive replicas produced by soft lithography and PDMS moulding. The results showed that SLA, more than MJ, produced finer part resolution and finer tuning of feature geometry. Furthermore, as assessed by zebrafish (Danio rerio) biotoxicity tests, there was no toxicity observed in SLA and MJ moulded PDMS replicas. We conclude that SLA, utilizing commercially available printers and resins, combined with PDMS soft-lithography, is a simple and easily accessible technique that lends its self particularly well to the fabrication of biocompatible millifluidic devices, highly suited to the in-situ analysis of small model organisms. Full article
(This article belongs to the Special Issue 3D Printed Microfluidic Devices)
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11 pages, 3781 KiB  
Article
Highly Fluorinated Methacrylates for Optical 3D Printing of Microfluidic Devices
by Frederik Kotz, Patrick Risch, Dorothea Helmer and Bastian E. Rapp
Micromachines 2018, 9(3), 115; https://doi.org/10.3390/mi9030115 - 08 Mar 2018
Cited by 45 | Viewed by 8282
Abstract
Highly fluorinated perfluoropolyether (PFPE) methacrylates are of great interest for transparent and chemically resistant microfluidic chips. However, so far only a few examples of material formulations for three-dimensional (3D) printing of these polymers have been demonstrated. In this paper we show that microfluidic [...] Read more.
Highly fluorinated perfluoropolyether (PFPE) methacrylates are of great interest for transparent and chemically resistant microfluidic chips. However, so far only a few examples of material formulations for three-dimensional (3D) printing of these polymers have been demonstrated. In this paper we show that microfluidic chips can be printed using these highly fluorinated polymers by 3D stereolithography printing. We developed photocurable resin formulations that can be printed in commercial benchtop stereolithography printers. We demonstrate that the developed formulations can be printed with minimal cross-sectional area of 600 µm for monolithic embedded microfluidic channels and 200 µm for open structures. The printed and polymerized PFPE methacrylates show a good transmittance above 70% at wavelengths between 520–900 nm and a high chemical resistance when being exposed to organic solvents. Microfluidic mixers were printed to demonstrate the great variability of different designs that can be printed using stereolithography. Full article
(This article belongs to the Special Issue 3D Printed Microfluidic Devices)
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11 pages, 4156 KiB  
Article
Design, Preparation and Performance Study of On-Chip Flow-Through Amperometric Sensors with an Integrated Ag/AgCl Reference Electrode
by He Zhang, Rongyan Chuai, Xin Li and Bing Zhang
Micromachines 2018, 9(3), 114; https://doi.org/10.3390/mi9030114 - 07 Mar 2018
Cited by 5 | Viewed by 4505
Abstract
To improve the reference potential stability of on-chip amperometric sensors, we propose a novel integrated Ag/AgCl reference electrode structure. This structure can refresh the saturated potassium chloride filling solution surrounding the Ag/AgCl electrode. We then designed a flow-through amperometric sensor and a multilayer [...] Read more.
To improve the reference potential stability of on-chip amperometric sensors, we propose a novel integrated Ag/AgCl reference electrode structure. This structure can refresh the saturated potassium chloride filling solution surrounding the Ag/AgCl electrode. We then designed a flow-through amperometric sensor and a multilayer microfluidic chip based on the integrated reference electrode. In order to improve the detection signal strength of the flow-through sensor, a numerical simulation model was established. The simulation results showed that a combination of (1) using a step-type detection cell structure that maintains micro-channel width while reducing micro-channel height, and (2) controlling the sample flow rate to limit the mass transfer of the sensor surface effectively, improves the detection signal strength. The step-type detection cell structure had dimensions of 200 μm × 200 μm × 100 μm (length × width × height), and the electroosmotic flow driving voltage was 120 V/cm. Finally, successful trace detection of Mg2+ and Pb2+ in the water was achieved using the amperometric sensor and microfluidic chip: detection limits were 5 μmol/L and 84 μmol/L. The preparation of an on-chip flow-through amperometric sensor with an integrated Ag/AgCl reference electrode will facilitate improved portability of microfluidic detection technology. Full article
(This article belongs to the Special Issue Microfluidic Sensors)
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25 pages, 8746 KiB  
Article
Adaptive Absolute Ego-Motion Estimation Using Wearable Visual-Inertial Sensors for Indoor Positioning
by Ya Tian, Zhe Chen, Shouyin Lu and Jindong Tan
Micromachines 2018, 9(3), 113; https://doi.org/10.3390/mi9030113 - 06 Mar 2018
Cited by 4 | Viewed by 3881
Abstract
This paper proposes an adaptive absolute ego-motion estimation method using wearable visual-inertial sensors for indoor positioning. We introduce a wearable visual-inertial device to estimate not only the camera ego-motion, but also the 3D motion of the moving object in dynamic environments. Firstly, a [...] Read more.
This paper proposes an adaptive absolute ego-motion estimation method using wearable visual-inertial sensors for indoor positioning. We introduce a wearable visual-inertial device to estimate not only the camera ego-motion, but also the 3D motion of the moving object in dynamic environments. Firstly, a novel method dynamic scene segmentation is proposed using two visual geometry constraints with the help of inertial sensors. Moreover, this paper introduces a concept of “virtual camera” to consider the motion area related to each moving object as if a static object were viewed by a “virtual camera”. We therefore derive the 3D moving object’s motion from the motions for the real and virtual camera because the virtual camera’s motion is actually the combined motion of both the real camera and the moving object. In addition, a multi-rate linear Kalman-filter (MR-LKF) as our previous work was selected to solve both the problem of scale ambiguity in monocular camera tracking and the different sampling frequencies of visual and inertial sensors. The performance of the proposed method is evaluated by simulation studies and practical experiments performed in both static and dynamic environments. The results show the method’s robustness and effectiveness compared with the results from a Pioneer robot as the ground truth. Full article
(This article belongs to the Special Issue MEMS Technology for Biomedical Imaging Applications)
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2 pages, 145 KiB  
Editorial
Editorial for the Special Issue on Wireless Microdevices and Systems for Biomedical Applications
by Paulo Mateus Mendes
Micromachines 2018, 9(3), 112; https://doi.org/10.3390/mi9030112 - 05 Mar 2018
Viewed by 2313
Abstract
Wireless microdevices are getting smaller and smaller, and in this special issue seven papers address a few miniaturization challenges in the biomedical field, which are common across different applications. Kargaran et al. [1] proposes a new ultra-low-voltage ultra-low-power LNA, where the reduced current [...] Read more.
Wireless microdevices are getting smaller and smaller, and in this special issue seven papers address a few miniaturization challenges in the biomedical field, which are common across different applications. Kargaran et al. [1] proposes a new ultra-low-voltage ultra-low-power LNA, where the reduced current consumption of only 160 μA, on a supply as low as 0.18 V, has potential to enable future RF receivers for ultra-low-power implantable devices [...]
Full article
(This article belongs to the Special Issue Wireless Microdevices and Systems for Biomedical Applications)
22 pages, 3757 KiB  
Article
Modeling and Closed Loop Flight Testing of a Fixed Wing Micro Air Vehicle
by Harikumar Kandath, Jinraj V. Pushpangathan, Titas Bera, Sidhant Dhall and M. Seetharama Bhat
Micromachines 2018, 9(3), 111; https://doi.org/10.3390/mi9030111 - 04 Mar 2018
Cited by 13 | Viewed by 4275
Abstract
This paper presents the nonlinear six degrees of freedom dynamic modeling of a fixed wing micro air vehicle. The static derivatives of the micro air vehicle are obtained through the wind tunnel testing. The propeller effects on the lift, drag, pitching moment and [...] Read more.
This paper presents the nonlinear six degrees of freedom dynamic modeling of a fixed wing micro air vehicle. The static derivatives of the micro air vehicle are obtained through the wind tunnel testing. The propeller effects on the lift, drag, pitching moment and side force are quantified through wind tunnel testing. The dynamic derivatives are obtained through empirical relations available in the literature. The trim conditions are computed for a straight and constant altitude flight condition. The linearized longitudinal and lateral state space models are obtained about trim conditions. The variations in short period mode, phugoid mode, Dutch roll mode, roll subsidence mode and spiral mode with respect to different trim operating conditions is presented. A stabilizing static output feedback controller is designed using the obtained model. Successful closed loop flight trials are conducted with the static output feedback controller. Full article
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18 pages, 5300 KiB  
Article
Multi-Objective Optimizations of a Serpentine Micromixer with Crossing Channels at Low and High Reynolds Numbers
by Wasim Raza, Sang-Bum Ma and Kwang-Yong Kim
Micromachines 2018, 9(3), 110; https://doi.org/10.3390/mi9030110 - 04 Mar 2018
Cited by 18 | Viewed by 3987
Abstract
In order to maximize the mixing performance of a micromixer with an integrated three-dimensional serpentine and split-and-recombination configuration, multi-objective optimizations were performed at two different Reynolds numbers, 1 and 120, based on numerical simulation. Numerical analyses of fluid flow and mixing in the [...] Read more.
In order to maximize the mixing performance of a micromixer with an integrated three-dimensional serpentine and split-and-recombination configuration, multi-objective optimizations were performed at two different Reynolds numbers, 1 and 120, based on numerical simulation. Numerical analyses of fluid flow and mixing in the micromixer were performed using three-dimensional Navier-Stokes equations and convection-diffusion equation. Three dimensionless design variables that were related to the geometry of the micromixer were selected as design variables for optimization. Mixing index at the exit and pressure drop through the micromixer were employed as two objective functions. A parametric study was carried out to explore the effects of the design variables on the objective functions. Latin hypercube sampling method as a design-of-experiment technique has been used to select design points in the design space. Surrogate modeling of the objective functions was performed by using radial basis neural network. Concave Pareto-optimal curves comprising of Pareto-optimal solutions that represents the trade-off between the objective functions were obtained using a multi-objective genetic algorithm at Re = 1 and 120. Through the optimizations, maximum enhancements of 18.8% and 6.0% in mixing index were achieved at Re = 1 and 120, respectively. Full article
(This article belongs to the Special Issue Passive Micromixers)
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18 pages, 3774 KiB  
Article
Turing Instability-Driven Biofabrication of Branching Tissue Structures: A Dynamic Simulation and Analysis Based on the Reaction–Diffusion Mechanism
by Xiaolu Zhu and Hao Yang
Micromachines 2018, 9(3), 109; https://doi.org/10.3390/mi9030109 - 02 Mar 2018
Cited by 9 | Viewed by 4285
Abstract
Four-dimensional (4D) biofabrication techniques aim to dynamically produce and control three-dimensional (3D) biological structures that would transform their shapes or functionalities with time, when a stimulus is imposed or cell post-printing self-assembly occurs. The evolution of 3D branching patterns via self-assembly of cells [...] Read more.
Four-dimensional (4D) biofabrication techniques aim to dynamically produce and control three-dimensional (3D) biological structures that would transform their shapes or functionalities with time, when a stimulus is imposed or cell post-printing self-assembly occurs. The evolution of 3D branching patterns via self-assembly of cells is critical for the 4D biofabrication of artificial organs or tissues with branched geometry. However, it is still unclear how the formation and evolution of these branching patterns are biologically encoded. Here, we study the biofabrication of lung branching structures utilizing a simulation model based on Turing instability that raises a dynamic reaction–diffusion (RD) process of the biomolecules and cells. The simulation model incorporates partial differential equations of four variables, describing the tempo-spatial distribution of the variables in 3D over time. The simulation results present the formation and evolution process of 3D branching patterns over time and also interpret both the behaviors of side-branching and tip-splitting as the stalk grows and the fabrication style under an external concentration gradient of morphogen, through 3D visualization. This provides a theoretical framework for rationally guiding the 4D biofabrication of lung airway grafts via cellular self-organization, which would potentially reduce the complexity of future experimental research and number of trials. Full article
(This article belongs to the Special Issue Selected Papers from ICMEAS 2017)
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