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Micromachines, Volume 10, Issue 2 (February 2019)

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Open AccessArticle On-Chip Cell Incubator for Simultaneous Observation of Culture with and without Periodic Hydrostatic Pressure
Micromachines 2019, 10(2), 133; https://doi.org/10.3390/mi10020133 (registering DOI)
Received: 12 January 2019 / Revised: 15 February 2019 / Accepted: 15 February 2019 / Published: 17 February 2019
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Abstract
This paper proposes a microfluidic device which can perform simultaneous observation on cell growth with and without applying periodic hydrostatic pressure (Yokoyama et al. Sci. Rep. 2017, 7, 427). The device is called on-chip cell incubator. It is known that culture [...] Read more.
This paper proposes a microfluidic device which can perform simultaneous observation on cell growth with and without applying periodic hydrostatic pressure (Yokoyama et al. Sci. Rep. 2017, 7, 427). The device is called on-chip cell incubator. It is known that culture with periodic hydrostatic pressure benefits the elasticity of a cultured cell sheet based on the results in previous studies, but how the cells respond to such a stimulus during the culture is not yet clear. In this work, we focused on cell behavior under periodic hydrostatic pressure from the moment of cell seeding. The key advantage of the proposed device is that we can compare the results with and without periodic hydrostatic pressure while all other conditions were kept the same. According to the results, we found that cell sizes under periodic hydrostatic pressure increase faster than those under atmospheric pressure, and furthermore, a frequency-dependent fluctuation of cell size was found using Fourier analysis. Full article
(This article belongs to the Special Issue Microfluidics for Cell and Other Organisms)
Open AccessArticle A Silicon-based Coral-like Nanostructured Microfluidics to Isolate Rare Cells in Human Circulation: Validation by SK-BR-3 Cancer Cell Line and Its Utility in Circulating Fetal Nucleated Red Blood Cells
Micromachines 2019, 10(2), 132; https://doi.org/10.3390/mi10020132 (registering DOI)
Received: 24 January 2019 / Revised: 13 February 2019 / Accepted: 14 February 2019 / Published: 17 February 2019
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Abstract
Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). “Cell RevealTM system” is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform [...] Read more.
Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). “Cell RevealTM system” is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform is recently optimized to enhance the capture efficiency and system automation. In this study, spiking tests of SK-BR-3 breast cancer cells were used for the evaluation of capture efficiency. Then, peripheral bloods from 14 pregnant women whose fetuses have evidenced non-maternal genomic markers (e.g., de novo pathogenic copy number changes) were tested for the capture of circulating fetal nucleated red blood cells (fnRBCs). Captured cells were subjected to fluorescent in situ hybridization (FISH) on chip or recovered by an automated cell picker for molecular genetic analyses. The capture rate for the spiking tests is estimated as 88.1%. For the prenatal study, 2–71 fnRBCs were successfully captured from 2 mL of maternal blood in all pregnant women. The captured fnRBCs were verified to be from fetal origin. Our results demonstrated that the Cell RevealTM system has a high capture efficiency and can be used for fnRBC capture that is feasible for the genetic diagnosis of fetuses without invasive procedures. Full article
(This article belongs to the Special Issue Microfluidics for Cell and Other Organisms)
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Open AccessArticle A Microfluidic Micropipette Aspiration Device to Study Single-Cell Mechanics Inspired by the Principle of Wheatstone Bridge
Micromachines 2019, 10(2), 131; https://doi.org/10.3390/mi10020131 (registering DOI)
Received: 10 January 2019 / Revised: 11 February 2019 / Accepted: 11 February 2019 / Published: 16 February 2019
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Abstract
The biomechanical properties of single cells show great potential for early disease diagnosis and effective treatments. In this study, a microfluidic device was developed for quantifying the mechanical properties of a single cell. Micropipette aspiration was integrated into a microfluidic device that mimics [...] Read more.
The biomechanical properties of single cells show great potential for early disease diagnosis and effective treatments. In this study, a microfluidic device was developed for quantifying the mechanical properties of a single cell. Micropipette aspiration was integrated into a microfluidic device that mimics a classical Wheatstone bridge circuit. This technique allows us not only to effectively alter the flow direction for single-cell trapping, but also to precisely control the pressure exerted on the aspirated cells, analogous to the feature of the Wheatstone bridge that can precisely control bridge voltage and current. By combining the micropipette aspiration technique into the microfluidic device, we can effectively trap the microparticles and Hela cells as well as measure the deformability of cells. The Young’s modulus of Hela cells was evaluated to be 387 ± 77 Pa, which is consistent with previous micropipette aspiration studies. The simplicity, precision, and usability of our device show good potential for biomechanical trials in clinical diagnosis and cell biology research. Full article
(This article belongs to the Special Issue Microfluidics for Cell and Other Organisms)
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Open AccessArticle Phototactic Algae-Driven Unidirectional Transport of Submillimeter-Sized Cargo in a Microchannel
Micromachines 2019, 10(2), 130; https://doi.org/10.3390/mi10020130 (registering DOI)
Received: 18 January 2019 / Revised: 7 February 2019 / Accepted: 8 February 2019 / Published: 16 February 2019
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Abstract
The sensing and actuation capabilities of biological cells integrated with artificial components have been used to create autonomous microsystems. For creating autonomous microsystems, the unidirectional transport of a submillimeter-sized cargo with stimuli responsive bio-motors should be developed as a fundamental motion. This study [...] Read more.
The sensing and actuation capabilities of biological cells integrated with artificial components have been used to create autonomous microsystems. For creating autonomous microsystems, the unidirectional transport of a submillimeter-sized cargo with stimuli responsive bio-motors should be developed as a fundamental motion. This study aims to use Volvox as a light-controlled microrobot to achieve the unidirectional transport of a submillimeter-sized cargo. We show the fabrication of a guide structure, cargo, and light irradiation platform for a unidirectional actuation. The fundamental performances of each component were investigated, and the motions of Volvox were controlled in a microchamber with the developed light irradiation platform. All components were integrated to demonstrate the unidirectional actuation of a block by Volvox. We discuss the dynamics of the mechanical motions. Full article
(This article belongs to the Special Issue Micro/Nanomotors 2018)
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Open AccessArticle Detection of Hepatitis C Virus Core Protein in Serum Using Aptamer-Functionalized AFM Chips
Micromachines 2019, 10(2), 129; https://doi.org/10.3390/mi10020129 (registering DOI)
Received: 28 December 2018 / Revised: 8 February 2019 / Accepted: 11 February 2019 / Published: 15 February 2019
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Abstract
In the present study, we demonstrate atomic force microscopy (AFM)-based detection of hepatitis C virus (HCV) particles in serum samples using a chip with aptamer-functionalized surface (apta-based AFM chip). The target particles, containing core antigen of HCV (HCVcoreAg protein), were biospecifically captured onto [...] Read more.
In the present study, we demonstrate atomic force microscopy (AFM)-based detection of hepatitis C virus (HCV) particles in serum samples using a chip with aptamer-functionalized surface (apta-based AFM chip). The target particles, containing core antigen of HCV (HCVcoreAg protein), were biospecifically captured onto the chip surface from 1 mL of test solution containing 10 µL of serum collected from a hepatitis C patient. The registration of aptamer/antigen complexes on the chip surface was performed by AFM. The aptamers used in the present study were initially developed for therapeutic purposes; herein, these aptamers have been successfully utilized as probe molecules for HCVcoreAg detection in the presence of a complex protein matrix (human serum). The results obtained herein can be used for the development of detection systems that employ affine enrichment for protein detection. Full article
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Open AccessArticle Higher-Order Mode Suppression in Antiresonant Nodeless Hollow-Core Fibers
Micromachines 2019, 10(2), 128; https://doi.org/10.3390/mi10020128 (registering DOI)
Received: 16 January 2019 / Accepted: 14 February 2019 / Published: 15 February 2019
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Abstract
Negative curvature hollow-core fibers (NC-HCFs) are useful as gas sensors. We numerically analyze the single-mode performance of NC-HCFs. Both single-ring NC-HCFs and nested antiresonant fibers (NANFs) are investigated. When the size of the cladding tubes is properly designed, higher-order modes (HOMs) in the [...] Read more.
Negative curvature hollow-core fibers (NC-HCFs) are useful as gas sensors. We numerically analyze the single-mode performance of NC-HCFs. Both single-ring NC-HCFs and nested antiresonant fibers (NANFs) are investigated. When the size of the cladding tubes is properly designed, higher-order modes (HOMs) in the fiber core can be coupled with the cladding modes effectively and form high-loss supermodes. For the single-ring structure, we propose a novel NC-HCF with hybrid cladding tubes to enable suppression of the first two HOMs in the core simultaneously. For the nested structure, we find that cascaded coupling is necessary to maximize the loss of the HOMs in NANFs, and, as a result, NANFs with five nested tubes have an advantage in single-mode guidance performance. Moreover, a novel NANF with hybrid extended cladding tubes is proposed. In this kind of NANF, higher-order mode extinction ratios (HOMERs) of 105 and even 106 are obtained for the LP11 and LP21 modes, respectively, and a similar level of 105 for the LP02 modes. Good single-mode performance is maintained within a broad wavelength range. In addition, the loss of the LP01 modes in this kind of NANF is as low as 3.90 × 10−4 dB/m. Full article
(This article belongs to the Special Issue Optofluidics 2018)
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Open AccessArticle Incorporation of Phosphorus Impurities in a Silicon Nanowire Transistor with a Diameter of 5 nm
Micromachines 2019, 10(2), 127; https://doi.org/10.3390/mi10020127
Received: 15 November 2018 / Revised: 2 February 2019 / Accepted: 3 February 2019 / Published: 15 February 2019
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Abstract
Silicon nanowire (SiNW) is always accompanied by severe impurity segregation and inhomogeneous distribution, which deteriorates the SiNWs electrical characteristics. In this paper, a method for phosphorus doping incorporation in SiNW was proposed using plasma. It showed that this method had a positive effect [...] Read more.
Silicon nanowire (SiNW) is always accompanied by severe impurity segregation and inhomogeneous distribution, which deteriorates the SiNWs electrical characteristics. In this paper, a method for phosphorus doping incorporation in SiNW was proposed using plasma. It showed that this method had a positive effect on the doping concentration of the wires with a diameter ranging from 5 nm to 20 nm. Moreover, an SiNW transistor was assembled based on the nanowire with a 5 nm diameter. The device’s ION/IOFF ratio reached 104. The proposed incorporation method could be helpful to improve the effect of the dopants in the silicon nanowire at a nanometer scale. Full article
(This article belongs to the Special Issue Miniaturized Transistors)
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Open AccessArticle The Effect of the Anisotropy of Single Crystal Silicon on the Frequency Split of Vibrating Ring Gyroscopes
Micromachines 2019, 10(2), 126; https://doi.org/10.3390/mi10020126
Received: 10 January 2019 / Revised: 3 February 2019 / Accepted: 11 February 2019 / Published: 14 February 2019
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Abstract
This paper analyzes the effect of the anisotropy of single crystal silicon on the frequency split of the vibrating ring gyroscope, operated in the n=2 wineglass mode. Firstly, the elastic properties including elastic matrices and orthotropic elasticity values of (100) and [...] Read more.
This paper analyzes the effect of the anisotropy of single crystal silicon on the frequency split of the vibrating ring gyroscope, operated in the n = 2 wineglass mode. Firstly, the elastic properties including elastic matrices and orthotropic elasticity values of (100) and (111) silicon wafers were calculated using the direction cosines of transformed coordinate systems. The (111) wafer was found to be in-plane isotropic. Then, the frequency splits of the n = 2 mode ring gyroscopes of two wafers were simulated using the calculated elastic properties. The simulation results show that the frequency split of the (100) ring gyroscope is far larger than that of the (111) ring gyroscope. Finally, experimental verifications were carried out on the micro-gyroscopes fabricated using deep dry silicon on glass technology. The experimental results are sufficiently in agreement with those of the simulation. Although the single crystal silicon is anisotropic, all the results show that compared with the (100) ring gyroscope, the frequency split of the ring gyroscope fabricated using the (111) wafer is less affected by the crystal direction, which demonstrates that the (111) wafer is more suitable for use in silicon ring gyroscopes as it is possible to get a lower frequency split. Full article
(This article belongs to the Special Issue MEMS/NEMS Sensors: Fabrication and Application)
Open AccessReview Coaxial Electrohydrodynamic Atomization for the Production of Drug-Loaded Micro/Nanoparticles
Micromachines 2019, 10(2), 125; https://doi.org/10.3390/mi10020125
Received: 18 January 2019 / Revised: 10 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
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Abstract
Coaxial electrohydrodynamic atomization (CEHDA) presents a promising technology for preparing drug-loaded micro/nanoparticles with core-shell structures. Recently, CEHDA has attracted tremendous attention based on its specific advantages, including precise control over particle size and size distribution, reduced initial burst release and mild preparation conditions. [...] Read more.
Coaxial electrohydrodynamic atomization (CEHDA) presents a promising technology for preparing drug-loaded micro/nanoparticles with core-shell structures. Recently, CEHDA has attracted tremendous attention based on its specific advantages, including precise control over particle size and size distribution, reduced initial burst release and mild preparation conditions. Moreover, with different needles, CEHDA can produce a variety of drug-loaded micro/nanoparticles for drug delivery systems. In this review, we summarize recent advances in using double-layer structure, multilayer structure and multicomponent encapsulation strategies for developing micro/nanoparticles. The merits of applying multiplexed electrospray sources for high-throughput production are also highlighted. Full article
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Open AccessArticle In-DRAM Cache Management for Low Latency and Low Power 3D-Stacked DRAMs
Micromachines 2019, 10(2), 124; https://doi.org/10.3390/mi10020124
Received: 24 December 2018 / Revised: 3 February 2019 / Accepted: 5 February 2019 / Published: 14 February 2019
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Abstract
Recently, 3D-stacked dynamic random access memory (DRAM) has become a promising solution for ultra-high capacity and high-bandwidth memory implementations. However, it also suffers from memory wall problems due to long latency, such as with typical 2D-DRAMs. Although there are various cache management techniques [...] Read more.
Recently, 3D-stacked dynamic random access memory (DRAM) has become a promising solution for ultra-high capacity and high-bandwidth memory implementations. However, it also suffers from memory wall problems due to long latency, such as with typical 2D-DRAMs. Although there are various cache management techniques and latency hiding schemes to reduce DRAM access time, in a high-performance system using high-capacity 3D-stacked DRAM, it is ultimately essential to reduce the latency of the DRAM itself. To solve this problem, various asymmetric in-DRAM cache structures have recently been proposed, which are more attractive for high-capacity DRAMs because they can be implemented at a lower cost in 3D-stacked DRAMs. However, most research mainly focuses on the architecture of the in-DRAM cache itself and does not pay much attention to proper management methods. In this paper, we propose two new management algorithms for the in-DRAM caches to achieve a low-latency and low-power 3D-stacked DRAM device. Through the computing system simulation, we demonstrate the improvement of energy delay product up to 67%. Full article
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Open AccessArticle Effect of Process Parameters and Material Properties on Laser Micromachining of Microchannels
Micromachines 2019, 10(2), 123; https://doi.org/10.3390/mi10020123
Received: 17 January 2019 / Revised: 7 February 2019 / Accepted: 12 February 2019 / Published: 14 February 2019
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Abstract
Laser micromachining has emerged as a promising technique for mass production of microfluidic devices. However, control and optimization of process parameters, and design of substrate materials are still ongoing challenges for the widespread application of laser micromachining. This article reports a systematic study [...] Read more.
Laser micromachining has emerged as a promising technique for mass production of microfluidic devices. However, control and optimization of process parameters, and design of substrate materials are still ongoing challenges for the widespread application of laser micromachining. This article reports a systematic study on the effect of laser system parameters and thermo-physical properties of substrate materials on laser micromachining. Three dimensional transient heat conduction equation with a Gaussian laser heat source was solved using finite element based Multiphysics software COMSOL 5.2a. Large heat convection coefficients were used to consider the rapid phase transition of the material during the laser treatment. The depth of the laser cut was measured by removing material at a pre-set temperature. The grid independent analysis was performed for ensuring the accuracy of the model. The results show that laser power and scanning speed have a strong effect on the channel depth, while the level of focus of the laser beam contributes in determining both the depth and width of the channel. Higher thermal conductivity results deeper in cuts, in contrast the higher specific heat produces shallower channels for a given condition. These findings can help in designing and optimizing process parameters for laser micromachining of microfluidic devices. Full article
(This article belongs to the collection Laser Micromachining and Microfabrication)
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Open AccessArticle Development of A New Type of 2-DOF Piezo-Actuated Pseudo-Decoupled Compliant Mechanism for Elliptical Vibration Machining
Micromachines 2019, 10(2), 122; https://doi.org/10.3390/mi10020122
Received: 19 January 2019 / Revised: 2 February 2019 / Accepted: 11 February 2019 / Published: 13 February 2019
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Abstract
Currently, the elliptical vibration cutting/coining (EVC2) has been widely employed in fabricating various functional microstructure surfaces applied in many significant engineering fields. Therefore, for this study, a novel type of two-degree-of-freedom (2-DOF) piezoelectrically actuated pseudo-decoupled compliant mechanisms (PDCMs) with non-orthogonal decoupling [...] Read more.
Currently, the elliptical vibration cutting/coining (EVC2) has been widely employed in fabricating various functional microstructure surfaces applied in many significant engineering fields. Therefore, for this study, a novel type of two-degree-of-freedom (2-DOF) piezoelectrically actuated pseudo-decoupled compliant mechanisms (PDCMs) with non-orthogonal decoupling structures, which can exactly generate the strict ellipse trajectories, was developed for improving the forming accuracies of the EVC2 microstructures. First, the compliance matrices of 2-DOF PDCMs were theoretically modeled using the popular finite beam-based matrix modeling (FBMM) and the matrix-based compliance modeling (MCM) methods, then finite element analysis (FEA) was adopted to verify the effectiveness of the built compliance model for the 2-DOF PDCM with arbitrary structure parameters. Second, the static FEA method was employed to systematically reveal the dependencies of the tracking accuracies of the elliptical trajectories on the decoupling structures of 2-DOF PDCMs. Moreover, their main dynamic performances were also investigated through the FEA-based harmonic response analysis and modal analysis. On these bases, the critical angle of the decoupling structure was optimally set at 102.5° so that the PDCMs had minimum shape distortions of the ellipse trajectories. Thirdly, a series of experiments was conducted on this PDCM system for practically investigating its kinematic and dynamic performances. The actual aspect ratio between the major axis and minor axis of the ellipse trajectory was approximately 1.057, and the first-order and second-order resonant frequencies were 863 Hz and 1893 Hz, respectively. However, the obtained testing results demonstrated well the effectiveness and feasibility of 2-DOF PDCM systems in precisely tracking the ellipse trajectories with different geometric parameters. Several critical conclusions on this study are summarized in detail in the final section of this paper. Full article
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Open AccessArticle Fabrication of a Low Adhesive Superhydrophobic Surface on Ti6Al4V Alloys Using TiO2/Ni Composite Electrodeposition
Micromachines 2019, 10(2), 121; https://doi.org/10.3390/mi10020121
Received: 24 December 2018 / Revised: 31 January 2019 / Accepted: 12 February 2019 / Published: 13 February 2019
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Abstract
A superhydrophobic surface with low adhesion and good wear resistance was fabricated on Ti6Al4V substrates via TiO2/Ni composite electrodeposition, and subsequently modified with a fluoroalkylsilane (FAS) film. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and optical contact angle measurements were [...] Read more.
A superhydrophobic surface with low adhesion and good wear resistance was fabricated on Ti6Al4V substrates via TiO2/Ni composite electrodeposition, and subsequently modified with a fluoroalkylsilane (FAS) film. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and optical contact angle measurements were used to characterize the surface morphologies, chemical compositions, and surface wettability. The superhydrophobicity of the as-prepared surface results from the fabrication of a hierarchical structure and the assembly of low-surface energy fluorinated components. The as-prepared surface had a water contact angle as high as 162.6° and a sliding angle close to 1.8°. Scratch and abrasion tests showed that the superhydrophobic coating provided a superior wear resistance and stable mechanical abrasion protection. In addition, the influence of processing conditions, such as working voltage, deposited time, pH value, and TiO2 concentration, was also investigated. Full article
(This article belongs to the Section D:Materials and Processing)
Open AccessArticle Deep-Learning-Based Polar-Body Detection for Automatic Cell Manipulation
Micromachines 2019, 10(2), 120; https://doi.org/10.3390/mi10020120
Received: 19 January 2019 / Revised: 3 February 2019 / Accepted: 6 February 2019 / Published: 13 February 2019
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Abstract
Polar-body detection is an essential and crucial procedure in various automatic cell manipulations. The polar body can only be observed when it is located near the focal plane of the microscope, so we need to detect the polar body during cell rotation in [...] Read more.
Polar-body detection is an essential and crucial procedure in various automatic cell manipulations. The polar body can only be observed when it is located near the focal plane of the microscope, so we need to detect the polar body during cell rotation in cell manipulations. However, three-dimensional cell rotation by micropipette causes polar-body defocus and cell/polar-body deformation, which have not been discussed in existing image-level polar-body-detection approaches. Moreover, varying sizes of the polar bodies increase the difficulty of polar-body detection. In this paper, we propose a deep-learning-based framework to realize polar-body detection in cell rotation. The detection problem is interpreted as image segmentation, which separates the polar body from the background. Then, we improve U-net, which is a typical convolutional neural network (CNN) for medical-image segmentation, so that the network can be applied to polar-body detection, especially for the detection of defocused polar bodies and polar bodies of different sizes. For CNN training, we also designed a particular image-transformation method to simulate more cell-rotation situations, including cell- and polar-body deformation, so that the deformed polar body in cell rotation would be detected by the proposed method. Experiment results show that our method achieves high detection accuracy of 98.7% on a test dataset of 1000 images, and performs well in cell-rotation processes. This method can be applied to various automatic cell manipulations in the future. Full article
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Open AccessArticle Comparison of Argon and Oxygen Plasma Treatments for Ambient Room-Temperature Wafer-Scale Au–Au Bonding Using Ultrathin Au Films
Micromachines 2019, 10(2), 119; https://doi.org/10.3390/mi10020119
Received: 20 December 2018 / Revised: 5 February 2019 / Accepted: 7 February 2019 / Published: 13 February 2019
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Abstract
Au–Au surface activated bonding is promising for room-temperature bonding. The use of Ar plasma vs. O2 plasma for pretreatment was investigated for room-temperature wafer-scale Au–Au bonding using ultrathin Au films (<50 nm) in ambient air. The main difference between Ar plasma and [...] Read more.
Au–Au surface activated bonding is promising for room-temperature bonding. The use of Ar plasma vs. O2 plasma for pretreatment was investigated for room-temperature wafer-scale Au–Au bonding using ultrathin Au films (<50 nm) in ambient air. The main difference between Ar plasma and O2 plasma is their surface activation mechanism: physical etching and chemical reaction, respectively. Destructive razor blade testing revealed that the bonding strength of samples obtained using Ar plasma treatment was higher than the strength of bulk Si (surface energy of bulk Si: 2.5 J/m2), while that of samples obtained using O2 plasma treatment was low (surface energy: 0.1–0.2 J/m2). X-ray photoelectron spectroscopy analysis revealed that a gold oxide (Au2O3) layer readily formed with O2 plasma treatment, and this layer impeded Au–Au bonding. Thermal desorption spectroscopy analysis revealed that Au2O3 thermally desorbed around 110 °C. Annealing of O2 plasma-treated samples up to 150 °C before bonding increased the bonding strength from 0.1 to 2.5 J/m2 due to Au2O3 decomposition. Full article
(This article belongs to the Special Issue Heterogeneous Integration for Optical Micro and Nanosystems)
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Open AccessArticle Modeling of Knudsen Layer Effects in the Micro-Scale Backward-Facing Step in the Slip Flow Regime
Micromachines 2019, 10(2), 118; https://doi.org/10.3390/mi10020118
Received: 27 December 2018 / Revised: 25 January 2019 / Accepted: 2 February 2019 / Published: 12 February 2019
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Abstract
The effect of the Knudsen layer in the thermal micro-scale gas flows has been investigated. The effective mean free path model has been implemented in the open source computational fluid dynamics (CFD) code, to extend its applicability up to slip and early transition [...] Read more.
The effect of the Knudsen layer in the thermal micro-scale gas flows has been investigated. The effective mean free path model has been implemented in the open source computational fluid dynamics (CFD) code, to extend its applicability up to slip and early transition flow regime. The conventional Navier-Stokes constitutive relations and the first-order non-equilibrium boundary conditions are modified based on the effective mean free path, which depends on the distance from the solid surface. The predictive capability of the standard ‘Maxwell velocity slip—Smoluchwoski temperature jump’ and hybrid boundary conditions ‘Langmuir Maxwell velocity slip—Langmuir Smoluchwoski temperature jump’ in conjunction with the Knudsen layer formulation has been evaluated in the present work. Simulations are carried out over a nano-/micro-scale backward facing step geometry in which flow experiences adverse pressure gradient, separation and re-attachment. Results are validated against the direct simulation Monte Carlo (DSMC) data, and have shown significant improvement over the existing CFD solvers. Non-equilibrium effects on the velocity and temperature of gas on the surface of the backward facing step channel are studied by varying the flow Knudsen number, inlet flow temperature, and wall temperature. Results show that the modified solver with hybrid Langmuir based boundary conditions gives the best predictions when the Knudsen layer is incorporated, and the standard Maxwell-Smoluchowski can accurately capture momentum and the thermal Knudsen layer when the temperature of the wall is higher than the fluid flow. Full article
(This article belongs to the Special Issue Gas Flows in Microsystems)
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Open AccessArticle Measuring Ocular Aberrations Sequentially Using a Digital Micromirror Device
Micromachines 2019, 10(2), 117; https://doi.org/10.3390/mi10020117
Received: 5 January 2019 / Revised: 25 January 2019 / Accepted: 8 February 2019 / Published: 12 February 2019
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Abstract
The Hartmann–Shack wavefront sensor is widely used to measure aberrations in both astronomy and ophthalmology. Yet, the dynamic range of the sensor is limited by cross-talk between adjacent lenslets. In this study, we explore ocular aberration measurements with a recently-proposed variant of the [...] Read more.
The Hartmann–Shack wavefront sensor is widely used to measure aberrations in both astronomy and ophthalmology. Yet, the dynamic range of the sensor is limited by cross-talk between adjacent lenslets. In this study, we explore ocular aberration measurements with a recently-proposed variant of the sensor that makes use of a digital micromirror device for sequential aperture scanning of the pupil, thereby avoiding the use of a lenslet array. We report on results with the sensor using two different detectors, a lateral position sensor and a charge-coupled device (CCD) scientific camera, and explore the pros and cons of both. Wavefront measurements of a highly aberrated artificial eye and of five real eyes, including a highly myopic subject, are demonstrated, and the role of pupil sampling density, CCD pixel binning, and scanning speed are explored. We find that the lateral position sensor is mostly suited for high-power applications, whereas the CCD camera with pixel binning performs consistently well both with the artificial eye and for real-eye measurements, and can outperform a commonly-used wavefront sensor with highly aberrated wavefronts. Full article
(This article belongs to the Special Issue Optical MEMS)
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Open AccessArticle Microfluidic High-Migratory Cell Collector Suppressing Artifacts Caused by Microstructures
Micromachines 2019, 10(2), 116; https://doi.org/10.3390/mi10020116
Received: 17 January 2019 / Revised: 1 February 2019 / Accepted: 7 February 2019 / Published: 11 February 2019
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Abstract
The small number of high-migratory cancer cells in a cell population make studies on high-migratory cancer cells difficult. For the development of migration assays for such cancer cells, several microfluidic devices have been developed. However, they measure migration that is influenced by microstructures [...] Read more.
The small number of high-migratory cancer cells in a cell population make studies on high-migratory cancer cells difficult. For the development of migration assays for such cancer cells, several microfluidic devices have been developed. However, they measure migration that is influenced by microstructures and they collect not only high-migratory cells, but also surrounding cells. In order to find high-migratory cells in cell populations while suppressing artifacts and to collect these cells while minimizing damages, we developed a microfluidic high-migratory cell collector with the ability to sort cancer cells according to cellular migration and mechanical detachment. High-migratory cancer cells travel further from the starting line when all of the cells are seeded on the same starting line. The high-migratory cells are detached using a stretch of cell adhesive surface using a water-driven balloon actuator. Using this cell collector, we selected high-migratory HeLa cells that migrated about 100m in 12 h and collected the cells. Full article
(This article belongs to the Section B:Biology)
Open AccessArticle Graphene Oxide Decorated Nanometal-Poly(Anilino-Dodecylbenzene Sulfonic Acid) for Application in High Performance Supercapacitors
Micromachines 2019, 10(2), 115; https://doi.org/10.3390/mi10020115
Received: 1 December 2018 / Revised: 4 February 2019 / Accepted: 6 February 2019 / Published: 11 February 2019
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Abstract
Graphene oxide (GO) decorated with silver (Ag), copper (Cu) or platinum (Pt) nanoparticles that are anchored on dodecylbenzene sulfonic acid (DBSA)-doped polyaniline (PANI) were prepared by a simple one-step method and applied as novel materials for high performance supercapacitors. High-resolution transmission electron microscopy [...] Read more.
Graphene oxide (GO) decorated with silver (Ag), copper (Cu) or platinum (Pt) nanoparticles that are anchored on dodecylbenzene sulfonic acid (DBSA)-doped polyaniline (PANI) were prepared by a simple one-step method and applied as novel materials for high performance supercapacitors. High-resolution transmission electron microscopy (HRTEM) and high-resolution scanning electron microscopy (HRSEM) analyses revealed that a metal-decorated polymer matrix is embedded within the GO sheet. This caused the M/DBSA–PANI (M = Ag, Cu or Pt) particles to adsorb on the surface of the GO sheets, appearing as aggregated dark regions in the HRSEM images. The Fourier transform infrared (FTIR) spectroscopy studies revealed that GO was successfully produced and decorated with Ag, Cu or Pt nanoparticles anchored on DBSA–PANI. This was confirmed by the appearance of the GO signature epoxy C–O vibration band at 1040 cm−1 (which decreased upon the introduction of metal nanoparticle) and the PANI characteristic N–H stretching vibration band at 3144 cm−1 present only in the GO/M/DBSA–PANI systems. The composites were tested for their suitability as supercapacitor materials; and specific capacitance values of 206.4, 192.8 and 227.2 F·g−1 were determined for GO/Ag/DBSA–PANI, GO/Cu/DBSA–PANI and GO/Pt/DBSA–PANI, respectively. The GO/Pt/DBSA–PANI electrode exhibited the best specific capacitance value of the three electrodes and also had twice the specific capacitance value reported for Graphene/MnO2//ACN (113.5 F·g−1). This makes GO/Pt/DBSA–PANI a very promising organic supercapacitor material. Full article
(This article belongs to the Special Issue Carbon Based Electronic Devices)
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Open AccessCommunication The Impact of Hydrogen on Mechanical Properties; A New In Situ Nanoindentation Testing Method
Micromachines 2019, 10(2), 114; https://doi.org/10.3390/mi10020114
Received: 13 January 2019 / Revised: 4 February 2019 / Accepted: 6 February 2019 / Published: 11 February 2019
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Abstract
We have designed a new method for electrochemical hydrogen charging which allows us to charge very thin coarse-grained specimens from the bottom and perform nanomechanical testing on the top. As the average grain diameter is larger than the thickness of the sample, this [...] Read more.
We have designed a new method for electrochemical hydrogen charging which allows us to charge very thin coarse-grained specimens from the bottom and perform nanomechanical testing on the top. As the average grain diameter is larger than the thickness of the sample, this setup allows us to efficiently evaluate the mechanical properties of multiple single crystals with similar electrochemical conditions. Another important advantage is that the top surface is not affected by corrosion by the electrolyte. The nanoindentation results show that hydrogen reduces the activation energy for homogenous dislocation nucleation by approximately 15–20% in a (001) grain. The elastic modulus also was observed to be reduced by the same amount. The hardness increased by approximately 4%, as determined by load-displacement curves and residual imprint analysis. Full article
(This article belongs to the Special Issue Small Scale Deformation using Advanced Nanoindentation Techniques)
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Open AccessCommunication Self-Healing Flexible Conductive Film by Repairing Defects via Flowable Liquid Metal Droplets
Micromachines 2019, 10(2), 113; https://doi.org/10.3390/mi10020113
Received: 10 December 2018 / Revised: 18 January 2019 / Accepted: 1 February 2019 / Published: 11 February 2019
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Abstract
Self-healing flexible conductive films have been fabricated, evaluated, and applied. The film is composed of a fragile indium tin oxide (ITO) layer covered with sprayed liquid metal (LM) droplets. Self-healing of electrical conductivity is achieved via spontaneous capillary wicking of LM droplets into [...] Read more.
Self-healing flexible conductive films have been fabricated, evaluated, and applied. The film is composed of a fragile indium tin oxide (ITO) layer covered with sprayed liquid metal (LM) droplets. Self-healing of electrical conductivity is achieved via spontaneous capillary wicking of LM droplets into cracks/defects of the ITO film. The liquid metal adhering onto the ITO layer can also connect the ITO fragments during bending to keep the overall conductivity of the composite LM/ITO film stable. Stable and reversible electrowetting performance has been achieved with the composite LM/ITO as the conductive film, in either flat or curved states. Full article
(This article belongs to the Special Issue Optofluidics 2018)
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Open AccessArticle Development of a High Flow Rate 3-D Electroosmotic Flow Pump
Micromachines 2019, 10(2), 112; https://doi.org/10.3390/mi10020112
Received: 26 December 2018 / Revised: 23 January 2019 / Accepted: 2 February 2019 / Published: 11 February 2019
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Abstract
A low voltage 3D parallel electroosmotic flow (EOF) pump composed of two electrode layers and a fluid layer is proposed in this work. The fluid layer contains twenty parallel fluid channels and is set at the middle of the two electrode layers. The [...] Read more.
A low voltage 3D parallel electroosmotic flow (EOF) pump composed of two electrode layers and a fluid layer is proposed in this work. The fluid layer contains twenty parallel fluid channels and is set at the middle of the two electrode layers. The distance between fluid and electrode channels was controlled to be under 45 μm, to reduce the driving voltage. Room temperature liquid metal was directly injected into the electrode channels by syringe to form non-contact electrodes. Deionized (DI) water with fluorescent particles was used to test the pumping performance of this EOF pump. According to the experimental results, a flow rate of 5.69 nL/min was reached at a driving voltage of 2 V. The size of this pump is small, and it shows a great potential for implanted applications. This structure could be easily expanded for more parallel fluid channels and larger flow rate. Full article
(This article belongs to the Special Issue Micro/Nano-Chip Electrokinetics, Volume III)
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Open AccessArticle The Optimal Design of Modulation Angular Rate for MEMS-Based Rotary Semi-SINS
Micromachines 2019, 10(2), 111; https://doi.org/10.3390/mi10020111
Received: 6 January 2019 / Revised: 28 January 2019 / Accepted: 6 February 2019 / Published: 10 February 2019
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Abstract
In previous studies, the semi-strapdown inertial navigation system (SSINS), based on microelectromechanical system (MEMS) sensors, had realized cross-range measurement of attitude information of high-spinning projectiles through construction of a “spin reduction” platform of the roll axis. However, further improvement of its measurement accuracy [...] Read more.
In previous studies, the semi-strapdown inertial navigation system (SSINS), based on microelectromechanical system (MEMS) sensors, had realized cross-range measurement of attitude information of high-spinning projectiles through construction of a “spin reduction” platform of the roll axis. However, further improvement of its measurement accuracy has been difficult, due to the inertial sensor error. In order to enhance the navigational accuracy, a periodically rotating method is utilized to compensate for sensor error, which is called rotation modulation. At present, the rotation scheme, as one of the core technologies, has been studied by a lot of researchers. It is known that the modulation angular rate is the main factor affecting the effectiveness of error modulation. Different from the long-endurance and low-dynamic motion characteristics of ships, however, the short-endurance and high-dynamic characteristics of the high-spinning projectile not only require the modulation angular rate to be as fast as possible but, also, the influence of the rotation speed error caused by rotating mechanism errors cannot be ignored. Combined with the rotation speed error of the rotating mechanism, this paper explored the relationship between modulation angular rate, device error, and the navigation error, and then proposed a design method for optimal modulation angular rate. Experiments were carried out to validate the performance of the method. In addition, the proposed method is applicable for rotation modulation systems with different types of motors as the rotating mechanism. Full article
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Open AccessArticle Elastic Turbulence of Aqueous Polymer Solution in Multi-Stream Micro-Channel Flow
Micromachines 2019, 10(2), 110; https://doi.org/10.3390/mi10020110
Received: 21 December 2018 / Revised: 31 January 2019 / Accepted: 3 February 2019 / Published: 7 February 2019
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Abstract
Viscous liquid flow in micro-channels is typically laminar because of the low Reynolds number constraint. However, by introducing elasticity into the fluids, the flow behavior could change drastically to become turbulent; this elasticity can be realized by dissolving small quantities of polymer molecules [...] Read more.
Viscous liquid flow in micro-channels is typically laminar because of the low Reynolds number constraint. However, by introducing elasticity into the fluids, the flow behavior could change drastically to become turbulent; this elasticity can be realized by dissolving small quantities of polymer molecules into an aqueous solvent. Our recent investigation has directly visualized the extension and relaxation of these polymer molecules in an aqueous solution. This elastic-driven phenomenon is known as ‘elastic turbulence’. Hitherto, existing studies on elastic flow instability are mostly limited to single-stream flows, and a comprehensive statistical analysis of a multi-stream elastic turbulent micro-channel flow is needed to provide additional physical understanding. Here, we investigate the flow field characteristics of elastic turbulence in a 3-stream contraction-expansion micro-channel flow. By applying statistical analyses and flow visualization tools, we show that the flow field bares many similarities to that of inertia-driven turbulence. More interestingly, we observed regions with two different types of power-law dependence in the velocity power spectra at high frequencies. This is a typical characteristic of two-dimensional turbulence and has hitherto not been reported for elastic turbulent micro-channel flows. Full article
(This article belongs to the Special Issue Nanoparticles on Microfluidic Platforms)
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Open AccessArticle Affordable Fabrication of Conductive Electrodes and Dielectric Films for a Paper-Based Digital Microfluidic Chip
Micromachines 2019, 10(2), 109; https://doi.org/10.3390/mi10020109
Received: 3 January 2019 / Revised: 2 February 2019 / Accepted: 3 February 2019 / Published: 7 February 2019
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Abstract
In order to fabricate a digital microfluidic (DMF) chip, which requires a patterned array of electrodes coated with a dielectric film, we explored two simple methods: Ballpoint pen printing to generate the electrodes, and wrapping of a dielectric plastic film to coat the [...] Read more.
In order to fabricate a digital microfluidic (DMF) chip, which requires a patterned array of electrodes coated with a dielectric film, we explored two simple methods: Ballpoint pen printing to generate the electrodes, and wrapping of a dielectric plastic film to coat the electrodes. For precise and programmable printing of the patterned electrodes, we used a digital plotter with a ballpoint pen filled with a silver nanoparticle (AgNP) ink. Instead of using conventional material deposition methods, such as chemical vapor deposition, printing, and spin coating, for fabricating the thin dielectric layer, we used a simple method in which we prepared a thin dielectric layer using pre-made linear, low-density polyethylene (LLDPE) plastic (17-μm thick) by simple wrapping. We then sealed it tightly with thin silicone oil layers so that it could be used as a DMF chip. Such a treated dielectric layer showed good electrowetting performance for a sessile drop without contact angle hysteresis under an applied voltage of less than 170 V. By using this straightforward fabrication method, we quickly and affordably fabricated a paper-based DMF chip and demonstrated the digital electrofluidic actuation and manipulation of drops. Full article
(This article belongs to the Special Issue Micro- and Nanofluidics for Bionanoparticle Analysis)
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Open AccessArticle Towards an Ultra-Sensitive Temperature Sensor for Uncooled Infrared Sensing in CMOS–MEMS Technology
Micromachines 2019, 10(2), 108; https://doi.org/10.3390/mi10020108
Received: 10 January 2019 / Revised: 27 January 2019 / Accepted: 1 February 2019 / Published: 6 February 2019
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Abstract
Microbolometers and photon detectors are two main technologies to address the needs in Infrared Sensing applications. While the microbolometers in both complementary metal-oxide semiconductor (CMOS) and Micro-Electro-Mechanical Systems (MEMS) technology offer many advantages over photon detectors, they still suffer from nonlinearity and relatively [...] Read more.
Microbolometers and photon detectors are two main technologies to address the needs in Infrared Sensing applications. While the microbolometers in both complementary metal-oxide semiconductor (CMOS) and Micro-Electro-Mechanical Systems (MEMS) technology offer many advantages over photon detectors, they still suffer from nonlinearity and relatively low temperature sensitivity. This paper not only offers a reliable solution to solve the nonlinearity problem but also demonstrate a noticeable potential to build ultra-sensitive CMOS–MEMS temperature sensor for infrared (IR) sensing applications. The possibility of a 31× improvement in the total absolute frequency shift with respect to ambient temperature change is verified via both COMSOL (multiphysics solver) and theory. Nonlinearity problem is resolved by an operating temperature sensor around the beam bending point. The effect of both pull-in force and dimensional change is analyzed in depth, and a drastic increase in performance is achieved when the applied pull-in force between adjacent beams is kept as small as possible. The optimum structure is derived with a length of 57 µm and a thickness of 1 µm while avoiding critical temperature and, consequently, device failure. Moreover, a good match between theory and COMSOL is demonstrated, and this can be used as a guidance to build state-of-the-art designs. Full article
(This article belongs to the Special Issue Development of CMOS-MEMS/NEMS Devices)
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Open AccessArticle Heterogeneous Immunoassay Using Channels and Droplets in a Digital Microfluidic Platform
Micromachines 2019, 10(2), 107; https://doi.org/10.3390/mi10020107
Received: 15 December 2018 / Revised: 29 January 2019 / Accepted: 1 February 2019 / Published: 5 February 2019
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Abstract
This work presents a heterogeneous immunoassay using the integrated functionalities of a channel and droplets in a digital microfluidic (DMF) platform. Droplet functionality in DMF allows for the programmable manipulation of discrete sample and reagent droplets in the range of nanoliters. Pressure-driven channels [...] Read more.
This work presents a heterogeneous immunoassay using the integrated functionalities of a channel and droplets in a digital microfluidic (DMF) platform. Droplet functionality in DMF allows for the programmable manipulation of discrete sample and reagent droplets in the range of nanoliters. Pressure-driven channels become advantageous over droplets when sample must be washed, as the supernatant can be thoroughly removed in a convenient and rapid manner while the sample is immobilized. Herein, we demonstrate a magnetic bead-based, enzyme-linked immunosorbent assay (ELISA) using ~60 nL of human interleukin-6 (IL-6) sample. The wash buffer was introduced in the form of a wall-less virtual electrowetting channel by a syringe pump at the flow rate of 10 μL/min with ~100% bead retention rate. Critical parameters such as sample wash flow rate and bead retention rate were optimized for reliable assay results. A colorimetric readout was analyzed in the International Commission on Illumination (CIE) color space without the need for costly equipment. The concepts presented in this work are potentially applicable in rapid neonatal disease screening using a finger prick blood sample in a DMF platform. Full article
(This article belongs to the Special Issue 10th Anniversary of Micromachines)
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Open AccessCommunication Simple Fabrication of Structured Magnetic Metallic Nano-Platelets for Bio-Analytical Applications
Micromachines 2019, 10(2), 106; https://doi.org/10.3390/mi10020106
Received: 14 January 2019 / Revised: 31 January 2019 / Accepted: 1 February 2019 / Published: 3 February 2019
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Abstract
This short communication presents a simple method of preparation of thin-metal nano-platelets utilizing metal sputtering and lift-off photolithography. The method offers complete control over size, shape and properties of nano-platelets of sub-micrometer thickness. Platelets with a thickness of 50–200 nm and with defined [...] Read more.
This short communication presents a simple method of preparation of thin-metal nano-platelets utilizing metal sputtering and lift-off photolithography. The method offers complete control over size, shape and properties of nano-platelets of sub-micrometer thickness. Platelets with a thickness of 50–200 nm and with defined arbitrary shapes and sizes in the range of 15–300 μm were prepared from single or multiple metal layers by magnetron sputtering. Deposition of different metals in layers enabled fabrication of bi- or tri-metallic platelets with a magnetic core and differently composed surfaces. Highly reflective nano-platelets with a magnetic core allowed manipulation by magnetic fields, while different metallic surfaces served for functionalization by selected molecules. Submicron thin nano-platelets are extremely light (e.g., ~20 ng for a 100 μm × 100 μm × 0.1 μm gold nano-platelet) so that they can be attached to surfaces by only a few chemical bonds. At the same time their area is sufficiently large for simple optical recognition of their shape which is intended to label various characteristics depending on the specific surface functionalization of the given shape. Full article
(This article belongs to the Special Issue Nanoparticles on Microfluidic Platforms)
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Open AccessReview Micro-Surface and -Interfacial Tensions Measured Using the Micropipette Technique: Applications in Ultrasound-Microbubbles, Oil-Recovery, Lung-Surfactants, Nanoprecipitation, and Microfluidics
Micromachines 2019, 10(2), 105; https://doi.org/10.3390/mi10020105
Received: 14 December 2018 / Revised: 23 January 2019 / Accepted: 25 January 2019 / Published: 1 February 2019
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Abstract
This review presents a series of measurements of the surface and interfacial tensions we have been able to make using the micropipette technique. These include: equilibrium tensions at the air-water surface and oil-water interface, as well as equilibrium and dynamic adsorption of water-soluble [...] Read more.
This review presents a series of measurements of the surface and interfacial tensions we have been able to make using the micropipette technique. These include: equilibrium tensions at the air-water surface and oil-water interface, as well as equilibrium and dynamic adsorption of water-soluble surfactants and water-insoluble and lipids. At its essence, the micropipette technique is one of capillary-action, glass-wetting, and applied pressure. A micropipette, as a parallel or tapered shaft, is mounted horizontally in a microchamber and viewed in an inverted microscope. When filled with air or oil, and inserted into an aqueous-filled chamber, the position of the surface or interface meniscus is controlled by applied micropipette pressure. The position and hence radius of curvature of the meniscus can be moved in a controlled fashion from dimensions associated with the capillary tip (~5–10 μm), to back down the micropipette that can taper out to 450 μm. All measurements are therefore actually made at the microscale. Following the Young–Laplace equation and geometry of the capillary, the surface or interfacial tension value is simply obtained from the radius of the meniscus in the tapered pipette and the applied pressure to keep it there. Motivated by Franklin’s early experiments that demonstrated molecularity and monolayer formation, we also give a brief potted-historical perspective that includes fundamental surfactancy driven by margarine, the first use of a micropipette to circuitously measure bilayer membrane tensions and free energies of formation, and its basis for revolutionising the study and applications of membrane ion-channels in Droplet Interface Bilayers. Finally, we give five examples of where our measurements have had an impact on applications in micro-surfaces and microfluidics, including gas microbubbles for ultrasound contrast; interfacial tensions for micro-oil droplets in oil recovery; surface tensions and tensions-in-the surface for natural and synthetic lung surfactants; interfacial tension in nanoprecipitation; and micro-surface tensions in microfluidics. Full article
(This article belongs to the Special Issue Microscale Surface Tension and Its Applications)
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Open AccessReview Microfluidic Single-Cell Manipulation and Analysis: Methods and Applications
Micromachines 2019, 10(2), 104; https://doi.org/10.3390/mi10020104
Received: 19 December 2018 / Revised: 28 January 2019 / Accepted: 30 January 2019 / Published: 1 February 2019
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Abstract
In a forest of a hundred thousand trees, no two leaves are alike. Similarly, no two cells in a genetically identical group are the same. This heterogeneity at the single-cell level has been recognized to be vital for the correct interpretation of diagnostic [...] Read more.
In a forest of a hundred thousand trees, no two leaves are alike. Similarly, no two cells in a genetically identical group are the same. This heterogeneity at the single-cell level has been recognized to be vital for the correct interpretation of diagnostic and therapeutic results of diseases, but has been masked for a long time by studying average responses from a population. To comprehensively understand cell heterogeneity, diverse manipulation and comprehensive analysis of cells at the single-cell level are demanded. However, using traditional biological tools, such as petri-dishes and well-plates, is technically challengeable for manipulating and analyzing single-cells with small size and low concentration of target biomolecules. With the development of microfluidics, which is a technology of manipulating and controlling fluids in the range of micro- to pico-liters in networks of channels with dimensions from tens to hundreds of microns, single-cell study has been blooming for almost two decades. Comparing to conventional petri-dish or well-plate experiments, microfluidic single-cell analysis offers advantages of higher throughput, smaller sample volume, automatic sample processing, and lower contamination risk, etc., which made microfluidics an ideal technology for conducting statically meaningful single-cell research. In this review, we will summarize the advances of microfluidics for single-cell manipulation and analysis from the aspects of methods and applications. First, various methods, such as hydrodynamic and electrical approaches, for microfluidic single-cell manipulation will be summarized. Second, single-cell analysis ranging from cellular to genetic level by using microfluidic technology is summarized. Last, we will also discuss the advantages and disadvantages of various microfluidic methods for single-cell manipulation, and then outlook the trend of microfluidic single-cell analysis. Full article
(This article belongs to the Special Issue Microfluidics for Cell and Other Organisms)
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