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Micromachines, Volume 7, Issue 7 (July 2016) – 22 articles

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3461 KiB  
Article
Flexible Holographic Fabrication of 3D Photonic Crystal Templates with Polarization Control through a 3D Printed Reflective Optical Element
by David Lowell, David George, Jeffrey Lutkenhaus, Chris Tian, Murthada Adewole, Usha Philipose, Hualiang Zhang and Yuankun Lin
Micromachines 2016, 7(7), 128; https://doi.org/10.3390/mi7070128 - 21 Jul 2016
Cited by 12 | Viewed by 7376
Abstract
In this paper, we have systematically studied the holographic fabrication of three-dimensional (3D) structures using a single 3D printed reflective optical element (ROE), taking advantage of the ease of design and 3D printing of the ROE. The reflective surface was setup at non-Brewster [...] Read more.
In this paper, we have systematically studied the holographic fabrication of three-dimensional (3D) structures using a single 3D printed reflective optical element (ROE), taking advantage of the ease of design and 3D printing of the ROE. The reflective surface was setup at non-Brewster angles to reflect both s- and p-polarized beams for the interference. The wide selection of reflective surface materials and interference angles allow control of the ratio of s- and p-polarizations, and intensity ratio of side-beam to central beam for interference lithography. Photonic bandgap simulations have also indicated that both s and p-polarized waves are sometimes needed in the reflected side beams for maximum photonic bandgap size and certain filling fractions of dielectric inside the photonic crystals. The flexibility of single ROE and single exposure based holographic fabrication of 3D structures was demonstrated with reflective surfaces of ROEs at non-Brewster angles, highlighting the capability of the ROE technique of producing umbrella configurations of side beams with arbitrary angles and polarizations and paving the way for the rapid throughput of various photonic crystal templates. Full article
(This article belongs to the Special Issue Laser Micromachining and Microfabrication)
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<p>(<b>a</b>) Model of the lab-designed ROE in the 4 + 1 configuration, designed using CAD software. The reflective surfaces are mounted on the support structures to reflect a single circularly polarized laser beam; (<b>b</b>) schematic of wave vector configuration for four side beams and one central beam in the 4 + 1 configuration; (<b>c</b>) schematic of an aperture for beam selection; (<b>d</b>) photonic band structure for one of holographic photonic crystals; and (<b>e</b>) plot of maximum bandgap size and filling fraction of dielectric that produces maximum bandgap for the PhCs that can be fabricated using a reflective surface with refractive index n and angle of incidence 67°.</p>
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<p>(<b>a</b>) Cross-section view SEM of over-exposed sample formed with 4 + 1 configuration ROE; (<b>b</b>,<b>c</b>) Top-view SEM of holographically fabricated, well-developed 3D structures with 4 + 1 configuration ROE with large areas showing no diffraction pattern (b) and enlarged view (c); Fabricated (<b>d</b>) and (<b>e</b>) simulated cross-sectional view of 3D structure formed with 4 + 1 configuration. The structure is not uniform as was expected due to a designed shift in the angle of incidence of a side beam. The dark-red solid line is in parallel with the sample surface and the yellow dashed line indicates the orientation of the holographic structures.</p>
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<p>(<b>a</b>) Simulated top view of the 5 + 1 interference pattern and (<b>b</b>) atomic force micrograph (AFM) of fabricated quasi-crystals in DPHPA using a 5 + 1 configuration ROE. Five-circle clusters, pentagons, sun-like shapes of ten lines and decagons are drawn for eye guidance; (<b>c</b>) simulated interference patterns showing the front and back sides of a cubic volume; (<b>d</b>–<b>f</b>) cross-section SEM images of fabricated 3D quasicrystals in SU-8 cut in different orientation revealing various structural information; and (<b>g</b>) a side view of simulated 3D interference pattern due to 5 + 1 beams.</p>
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<p>(<b>a</b>) SEM of cross-section of not fully developed 3D PhCs in SU-8 but cut in an orientation where layer-by-layer pattern can be seen; (<b>b</b>) SEM of top-view of fabricated structures with six-fold symmetry in SU-8. Yellow lines indicate the orientation of structures in different layers. The hexagonal structure and the lattice constant Λ are indicated by the green hexagon and red arrow, respectively, for eye guidance; (<b>c</b>) SEM of the cross section of fabricated 3D PhCs in SU-8 and (<b>d</b>) the simulated interference pattern. Yellow lines indicate analogous fabricated and simulated structures; (<b>e</b>) measured FTIR reflection spectra from SU-8 PhCs and overexposed SU-8 film without any structures.</p>
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<p>(<b>a</b>) Diffraction pattern from fabricated 3D photonic crystal template in SU-8 using 532 nm laser; (<b>b</b>) top-view of simulated interference among pure s-wave side beams plus the central circularly polarized beam; (<b>c</b>) among pure p-wave side beams plus the central circularly polarized beam; (<b>d</b>) among side beams with both s- and p-waves plus the central circularly polarized beam. Interference patterns generated with 4 + 1 and 6 + 1 configurations are shown in top and bottom row in (b,c,d), respectively. Circles indicate the corresponding locations of high intensity spots. Dotted circles indicate the spots located at the bottom as shown in the side view in the insert in (c).</p>
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3388 KiB  
Article
Quantification of Vortex Generation Due to Non-Equilibrium Electrokinetics at the Micro/Nanochannel Interface: Particle Tracking Velocimetry
by Seung Jun Lee, Kilsung Kwon, Tae-Joon Jeon, Sun Min Kim and Daejoong Kim
Micromachines 2016, 7(7), 127; https://doi.org/10.3390/mi7070127 - 21 Jul 2016
Cited by 4 | Viewed by 4752
Abstract
We describe a quantitative study of vortex generation due to non-equilibrium electrokinetics near a micro/nanochannel interface. The microfluidic device is comprised of a microchannel with a set of nanochannels. These perm-selective nanochannels induce flow instability and thereby produce strong vortex generation. We performed [...] Read more.
We describe a quantitative study of vortex generation due to non-equilibrium electrokinetics near a micro/nanochannel interface. The microfluidic device is comprised of a microchannel with a set of nanochannels. These perm-selective nanochannels induce flow instability and thereby produce strong vortex generation. We performed tracking visualization of fluorescent microparticles to obtain velocity fields. Particle tracking enables the calculation of an averaged velocity field and the velocity fluctuations. We characterized the effect of applied voltages and electrolyte concentrations on vortex formation. The experimental results show that an increasing voltage or decreasing concentration results in a larger vortex region and a strong velocity fluctuation. We calculate the normalized velocity fluctuation—whose meaning is comparable to turbulent intensity—and we found that it is as high as 0.12. This value is indicative of very efficient mixing, albeit with a small Reynolds number. Full article
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<p>Schematic of the microfluidic device. The red rectangle indicates the region for the results in <a href="#micromachines-07-00127-f003" class="html-fig">Figure 3</a>, <a href="#micromachines-07-00127-f004" class="html-fig">Figure 4</a> and <a href="#micromachines-07-00127-f006" class="html-fig">Figure 6</a>. The black rectangles indicate the region for the results in <a href="#micromachines-07-00127-f005" class="html-fig">Figure 5</a>.</p>
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<p>(<b>a</b>) Particle path lines with no voltage and (<b>b</b>) particle path lines with an applied voltage of 150 V.</p>
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<p>Velocity field particle tracking with (<b>a</b>) no applied voltage; (<b>b</b>) 50 V; (<b>c</b>) 100 V; and (<b>d</b>) 150 V.</p>
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<p>Region of influence of vortex generation versus (<b>a</b>) applied voltage and (<b>b</b>) KCl concentration.</p>
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<p>Speed distribution in (<b>a</b>) a non-vortex region and (<b>b</b>) a vortex region (see <a href="#micromachines-07-00127-f001" class="html-fig">Figure 1</a>).</p>
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<p>Normalized velocity fluctuation versus (<b>a</b>) applied voltage and (<b>b</b>) KCl concentration.</p>
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3508 KiB  
Review
Mimicking the Kidney: A Key Role in Organ-on-Chip Development
by Roberto Paoli and Josep Samitier
Micromachines 2016, 7(7), 126; https://doi.org/10.3390/mi7070126 - 20 Jul 2016
Cited by 35 | Viewed by 20722
Abstract
Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal [...] Read more.
Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal models. In this regard, promising advances have recently been made by the so-called “organ-on-chip” (OOC) technology. By combining cell culture with microfluidics, biomedical researchers have started to develop microengineered models of the functional units of human organs. With the capacity to mimic physiological microenvironments and vascular perfusion, OOC devices allow the reproduction of tissue- and organ-level functions. When considering drug testing, nephrotoxicity is a major cause of attrition during pre-clinical, clinical, and post-approval stages. Renal toxicity accounts for 19% of total dropouts during phase III drug evaluation—more than half the drugs abandoned because of safety concerns. Mimicking the functional unit of the kidney, namely the nephron, is therefore a crucial objective. Here we provide an extensive review of the studies focused on the development of a nephron-on-chip device. Full article
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<p>Trend in population ageing: (<b>a</b>) Population by broad age group: world, 1950–2100; (<b>b</b>) Proportion of the population aged 60 years or over: world and development regions 1950–2050. Reproduced from United Nations, <span class="html-italic">World Population Ageing</span>; 2013 [<a href="#B31-micromachines-07-00126" class="html-bibr">31</a>], with permission of United Nations Publications.</p>
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<p>Renal ultrafiltration and reabsorption across the main sections of the nephron. Ultrafiltration from blood to ultrafiltrate takes place in the glomerulus. Reabsorption occurs across the tubule; in each section, reabsorption percentages of filtered amount are shown for the most relevant substances [<a href="#B26-micromachines-07-00126" class="html-bibr">26</a>].</p>
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<p>Fabrication and operation of a proximal tubule on a chip by Jang et al. [<a href="#B75-micromachines-07-00126" class="html-bibr">75</a>]. (<b>a</b>) Device assembly, sandwiching together a PDMS channel, polyester membrane, and PDMS reservoir using plasma bonding; (<b>b</b>) Photograph showing the device, placed on a culture dish containing outer tubular fluid, connected to the fluidic setup. Reproduced from [<a href="#B75-micromachines-07-00126" class="html-bibr">75</a>] with permission of the Royal Society of Chemistry. All rights reserved.</p>
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<p>Design of the human kidney proximal tubule-on-a-chip by Ingber’s group [<a href="#B6-micromachines-07-00126" class="html-bibr">6</a>]. (<b>a</b>) The microfluidic device consists of two PDMS channels, resembling the proximal tubule and interstitial space, separated by an ECM-coated porous membrane. HPTECs are cultured on top of the membrane, in the presence of a physiological level of apical fluid shear stress. (<b>b</b>) Device assembly: The upper layer, polyester porous membrane, and lower layer are bonded together through surface plasma treatment. Reproduced from [<a href="#B6-micromachines-07-00126" class="html-bibr">6</a>] with permission of the Royal Society of Chemistry. All rights reserved.</p>
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<p>Kidney stone formation, from Wei and colleagues [<a href="#B81-micromachines-07-00126" class="html-bibr">81</a>]. (<b>a</b>) Green fluorescence protein (GFP) expression showing typical basolateral staining in the monolayer of cells on the microchannel wall; (<b>b</b>) Channel cross-section showing the distribution of key plasma membrane protein Na<sup>+</sup>/K<sup>+</sup>-ATPase. Scale bars are 200 μm; (<b>c</b>) Photograph of the device with circular cross-section. Reproduced from [<a href="#B81-micromachines-07-00126" class="html-bibr">81</a>] with permission of the Royal Society of Chemistry. All rights reserved.</p>
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<p>A Fibrin-Based Tissue-Engineered Renal Proximal Tubule for Bioartificial Kidney Devices: Development, Characterization and In Vitro Transport Study (2013). (<b>a</b>) Schematic and (<b>b</b>) image of the “lab-on-a-chip” hollow-fiber bioreactor. (<b>c</b>) Set-up for perfusion studies. Reprinted from [<a href="#B82-micromachines-07-00126" class="html-bibr">82</a>] under CC-BY 3.0 with permission of Hindawi Publishing Corporation.</p>
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<p>3D view of microfluidic four-organ-chip device by Maschmeyer et al. [<a href="#B7-micromachines-07-00126" class="html-bibr">7</a>], (footprint: 76 mm × 25 mm; height: 3 mm). Intestine (1), liver (2), skin (3), and kidney (4) tissue culture compartments are interconnected by a surrogate blood flow circuit (pink) and an excretory flow circuit (yellow). Reproduced from [<a href="#B7-micromachines-07-00126" class="html-bibr">7</a>] with permission of the Royal Society of Chemistry. All rights reserved.</p>
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5476 KiB  
Article
Wide Field-of-View Fluorescence Imaging with Optical-Quality Curved Microfluidic Chamber for Absolute Cell Counting
by Mohiuddin Khan Shourav, Kyunghoon Kim, Subin Kim and Jung Kyung Kim
Micromachines 2016, 7(7), 125; https://doi.org/10.3390/mi7070125 - 20 Jul 2016
Cited by 5 | Viewed by 6420
Abstract
Field curvature and other aberrations are encountered inevitably when designing a compact fluorescence imaging system with a simple lens. Although multiple lens elements can be used to correct most such aberrations, doing so increases system cost and complexity. Herein, we propose a wide [...] Read more.
Field curvature and other aberrations are encountered inevitably when designing a compact fluorescence imaging system with a simple lens. Although multiple lens elements can be used to correct most such aberrations, doing so increases system cost and complexity. Herein, we propose a wide field-of-view (FOV) fluorescence imaging method with an unconventional optical-quality curved sample chamber that corrects the field curvature caused by a simple lens. Our optics simulations and proof-of-concept experiments demonstrate that a curved substrate with lens-dependent curvature can reduce greatly the distortion in an image taken with a conventional planar detector. Following the validation study, we designed a curved sample chamber that can contain a known amount of sample volume and fabricated it at reasonable cost using plastic injection molding. At a magnification factor of approximately 0.6, the curved chamber provides a clear view of approximately 119 mm2, which is approximately two times larger than the aberration-free area of a planar chamber. Remarkably, a fluorescence image of microbeads in the curved chamber exhibits almost uniform intensity over the entire field even with a simple lens imaging system, whereas the distorted boundary region has much lower brightness than the central area in the planar chamber. The absolute count of white blood cells stained with a fluorescence dye was in good agreement with that obtained by a commercially available conventional microscopy system. Hence, a wide FOV imaging system with the proposed curved sample chamber would enable us to acquire an undistorted image of a large sample volume without requiring a time-consuming scanning process in point-of-care diagnostic applications. Full article
(This article belongs to the Special Issue MEMS/NEMS for Biomedical Imaging and Sensing)
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<p>(<b>a</b>) Optical prescription for prototype curved-substrate imaging system, designed for a wavelength of 560 nm. A single commercial lens was used for imaging. All dimensions are in millimeters. (<b>b</b>) Schematic of experimental setup.</p>
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<p>(<b>a</b>) 3D model of curved sample chamber composed of an upper window (gray color) and a lower substrate (black color). A sample solution is introduced into the gap of 100-μm thickness between those two separable parts through one of the holes in the lower substrate. The other three holes are air vents. (Scale bar = 10 mm). (<b>b</b>) Curved sample chamber fabricated by plastic injection molding technique. The upper window is optically clear for image acquisition and the lower substrate is colored black to minimize light reflection at the surface.</p>
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<p>(<b>a</b>) A schematic of the cross-sectional view of the curved sample chamber and suspended cells in the gap between upper window and lower substrate; and (<b>b</b>) loading of cell suspension with a micropipette is facilitated by air vent holes made through the lower substrate as shown in (<b>a</b>).</p>
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<p>Ray tracing simulation of astigmatism field curvature. Ray tracing of a simple biconvex lens for: (<b>a</b>) flat substrate; and (<b>c</b>) curved substrate. The grayscale images in (<b>b</b>,<b>d</b>) were acquired using the flat and the curved substrates, where the image plane was kept flat. The images in (<b>b</b>,<b>d</b>) represent 0, 3, and 6 mm sample substrate height. The field curvature graphs for the flat and the curved substrates are shown in (<b>e</b>,<b>f</b>), respectively, where the blue and red lines denote tangential and sagittal surfaces.</p>
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<p>Analytical characterization of simple imaging system for flat and curved substrates. The spot size diagrams include a circle showing the Airy disk (9.87 μm in radius) for the flat and the curved substrates in (<b>a</b>,<b>d</b>), respectively. (<b>b</b>,<b>e</b>) MTF and (<b>c</b>,<b>f</b>) PSF of flat and curved substrates, respectively. In the MTFs, the black line shows the diffraction limit, and the red and pink lines represent the on- and off-axis image fields, respectively.</p>
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<p>Change in surface power and object curvature with change in curvature radius of lens. These radii of the lens consider both sides of biconvex lens, and have the same focal length as the radius.</p>
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<p>Imaging performance of single-lens fluorescence microscopy with curved sample chamber. Fluorescence images taken for beads of diameter 10 μm for: (<b>a</b>) planar; and (<b>b</b>) curved sample chambers. The fluorescent microbeads are distributed uniformly over the entire FOV. The intensity profiles of the bead images are shown in (<b>c</b>,<b>d</b>). As observed for the curved substrate, a wider area of the bead image is more focused in (<b>b</b>), and the aberration is lower than that in (<b>a</b>). (Scale bar = 1 mm).</p>
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<p>Fluorescence images of stained white blood cells in small and large field imaging. (<b>a</b>) Microscopic image of flat chamber. The inset white boxes in (<b>b</b>,<b>c</b>) are of the same size in the microscopy images of the flat and curved chambers. (<b>d</b>,<b>e</b>) Cropped areas of the flat and curved chamber images, where (ii) denotes the center part of an image. All cropped images are of the same size. The cell counts in the center (ii) were similar for both chambers. The bars in (<b>b</b>,<b>c</b>) represent a scale of 1 mm, while those in the other figures represent a scale of 200 µm.</p>
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<p>(<b>a</b>) WBC count obtained using planar chamber is remarkably different from the reference cell count obtained with conventional microscopy; and (<b>b</b>) WBC concentrations of 10%–70% with an interval of 10% and 100% were compared for absolute counting obtained by microscopic, flat, and curved chamber imaging. The count obtained with the curved chamber is close to that obtained with conventional microscopy. However, the corresponding result with the flat chamber differs considerably for large fields.</p>
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<p>(<b>a</b>–<b>c</b>) The reference, flat, and curved chamber images with 500 µm<sup>2</sup> white boxes inside, respectively (scale bar = 0.5 mm); (<b>d</b>–<b>f</b>) the normalized intensity profiles of a fluorescently-labeled WBC in those three images; and (<b>g</b>) the size of the fluorescent WBCs measured with microscopy, and flat and curved imaging, represented by Ref, Flat, and Curved on the <span class="html-italic">x</span>-axis of the graph, respectively. The range of WBC size is 16–20 µm. The normalized intensity profile of the fluorescence shows the size of the SYTO-stained WBC in pixels, and the inset images are cropped from the center part of the processed image.</p>
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1637 KiB  
Article
Locally-Actuated Graphene-Based Nano-Electro-Mechanical Switch
by Jian Sun, Manoharan Muruganathan, Nozomu Kanetake and Hiroshi Mizuta
Micromachines 2016, 7(7), 124; https://doi.org/10.3390/mi7070124 - 19 Jul 2016
Cited by 22 | Viewed by 5612
Abstract
The graphene nano-electro-mechanical switches are promising components due to their outstanding switching performance. However, most of the reported devices suffered from a large actuation voltages, hindering them from the integration in the conventional complementary metal-oxide-semiconductor (CMOS) circuit. In this work, we demonstrated the [...] Read more.
The graphene nano-electro-mechanical switches are promising components due to their outstanding switching performance. However, most of the reported devices suffered from a large actuation voltages, hindering them from the integration in the conventional complementary metal-oxide-semiconductor (CMOS) circuit. In this work, we demonstrated the graphene nano-electro-mechanical switches with the local actuation electrode via conventional nanofabrication techniques. Both cantilever-type and double-clamped beam switches were fabricated. These devices exhibited the sharp switching, reversible operation cycles, high on/off ratio, and a low actuation voltage of below 5 V, which were compatible with the CMOS circuit requirements. Full article
(This article belongs to the Special Issue Graphene Nano-Electro-Mechanical (NEM) Devices and Applications)
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<p>(<b>a</b>) Exfoliated graphene flake, black and red dots indicate the monolayer and bilayer regions, respectively; and (<b>b</b>) Raman spectra probed at locations marked as two color dots in (<b>a</b>). Green lines are the sub-peaks obtained from Lorentzian peak fitting. The arrow indicates the location of D band.</p>
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<p>Schematics of fabrication procedure of the graphene NEM switch with local top actuation electrode. T and B denote top and bottom electrodes, respectively. (<b>a</b>) Graphene exfoliation and bottom electrodes definition; (<b>b</b>) HSQ spin coating and pattering; (<b>c</b>) graphene etching in oxygen plasma; (<b>d</b>) definition of SiO<sub>2</sub> sacrificial layer; (<b>e</b>) definition of top electrode; (<b>f</b>) releasing graphene in HF.</p>
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<p>False color SEM image of a double-clamped beam graphene switch as-fabricated. T and B denote top and bottom electrodes, respectively.</p>
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<p>Electrical characterization of the switching performance of a double-clamped beam switch. The inset shows the two-terminal measurement configuration.</p>
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<p>SEM images of a graphene cantilever-type switch with a local top actuation electrode (<b>a</b>) before and (<b>b</b>) after the switching operation. The initial air gap <span class="html-italic">g</span><sub>0</sub> between the graphene and the top electrode is about 140 nm. The graphene cantilever is artificially colored in light blue. The scale bars are 500 nm.</p>
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<p>Electrical characterization of the switching performance of a cantilever-type switch. Inset: (<b>Lower</b>) two-terminal configuration and switch-off status, (<b>Right upper</b>) switch-on status, and (<b>Left upper</b>) I-V response after device failure.</p>
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8583 KiB  
Review
Microfluidic Approaches for Manipulating, Imaging, and Screening C. elegans
by Bhagwati P. Gupta and Pouya Rezai
Micromachines 2016, 7(7), 123; https://doi.org/10.3390/mi7070123 - 19 Jul 2016
Cited by 57 | Viewed by 10275
Abstract
The nematode C. elegans (worm) is a small invertebrate animal widely used in studies related to fundamental biological processes, disease modelling, and drug discovery. Due to their small size and transparent body, these worms are highly suitable for experimental manipulations. In recent years [...] Read more.
The nematode C. elegans (worm) is a small invertebrate animal widely used in studies related to fundamental biological processes, disease modelling, and drug discovery. Due to their small size and transparent body, these worms are highly suitable for experimental manipulations. In recent years several microfluidic devices and platforms have been developed to accelerate worm handling, phenotypic studies and screens. Here we review major tools and briefly discuss their usage in C. elegans research. Full article
(This article belongs to the Special Issue Micro/Nano Devices for Chemical Analysis)
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<p>Microfluidic devices for <span class="html-italic">C. elegans</span> sorting using (<b>A</b>) electrotaxis (Rezai et al. [<a href="#B10-micromachines-07-00123" class="html-bibr">10</a>], (<b>B</b>) mechanical microstructures (Solvas et al. [<a href="#B12-micromachines-07-00123" class="html-bibr">12</a>], (<b>C</b>) deflectable membranes (Dong et al. [<a href="#B17-micromachines-07-00123" class="html-bibr">17</a>], and (<b>D</b>) fiber-based fluorescent detection (Yan et al. [<a href="#B15-micromachines-07-00123" class="html-bibr">15</a>]). Reproduced with permission from The Royal Society of Chemistry. Panel (<b>A</b>) shows the electric trap-based sorting device. Loading chamber contains mixed stage worms. Sorted worms accumulate in the separation chamber and are recovered via unload channels. The smart maze concept is shown in panel (<b>B</b>). The four insets show worm orientation (inset <b>1</b>); flushing of small larvae (inset <b>2</b>); dimensions of the successful design (inset <b>3</b>); and successful recovery of adults in an experiment (inset <b>4</b>). The deflectable membrane device in panel (<b>C</b>) shows eight individual worm selection units (one of these connected with tubes). The fluidic and valve control channels are enlarged to show details. The fluidic path is squeezed upon activation of the control valve. The device in panel (<b>D</b>) contains inlets and outlets for worms and buffer. The optical fiber channels (LED 625 and 375 nm) are used to differentiate between wild-type and fluorescing worms. Refer to respective references for more details.</p>
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<p>Microfluidic devices for culturing and long-term studies of worms inside cultivation chambers while immobilization and imaging is performed by (<b>A</b>) tapered microchannels (Hulme et al. [<a href="#B23-micromachines-07-00123" class="html-bibr">23</a>] or (<b>B</b>) responsive hydrogels (Krajniak et al. [<a href="#B29-micromachines-07-00123" class="html-bibr">29</a>]. Reproduced with permission from The Royal Society of Chemistry. The tapered microchannels connected to growth chambers (panel (<b>A</b>)) allow single worms (early L4 stage) to enter into each chamber. Arrows indicate the direction of liquid flow. Once the worm has grown it is unable to escape the chamber. For imaging purposes, the worm is temporarily immobilized in the tapered region. Panel (<b>B</b>) The two sub-panels <b>B-i</b> and <b>B-ii</b> show the device that contains valves (<b>red</b>) to control fluid flow, channel for flowing heating liquid (<b>light</b> <b>blue</b>), and eight worm culturing chambers (two sets of four) and a central waste outlet tube connected to a loading channel (<b>green</b>). Refer to respective references for more details.</p>
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<p>Microfluidic devices to immobilize <span class="html-italic">C. elegans</span> using (<b>A</b>) deflectable membrane (Gilleland et al. [<a href="#B33-micromachines-07-00123" class="html-bibr">33</a>]; (<b>B</b>) tapered microchannels (Kopito and Levine [<a href="#B34-micromachines-07-00123" class="html-bibr">34</a>]); or (<b>C</b>) CO<sub>2</sub> exposure (Chokshi et al. [<a href="#B35-micromachines-07-00123" class="html-bibr">35</a>]. Reproduced with permissions from The Royal Society of Chemistry and Macmillan Publishers Ltd. Nature Protocols. Panel (<b>A</b>) shows the chip containing an array of narrow channels to apply suction pressure. Worm is loaded/removed through port-B and restrained by the narrow channel array. Pressure through port-A causes the compression layer to move downwards and immobilize the worm (explained on the right). Releasing the pressure allows the worm to be recovered. The WormSpa device, in panel (<b>B</b>), contains four regions for worm loading and distribution (<b>1</b>), egg chambers (<b>2</b>), egg collection (<b>3</b>), and outflow (<b>4</b>). The device for CO<sub>2</sub> based immobilization is shown in panel (<b>C</b>). It contains modules for behaviour assay (first row of pictures) and immobilization (second row of pictures). Refer to respective references for more details.</p>
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<p>Microfluidic devices for microinjection in (<b>A</b>) closed microchannels (Ghaemi [<a href="#B41-micromachines-07-00123" class="html-bibr">41</a>] and (<b>B</b>) open chambers (Song et al. [<a href="#B43-micromachines-07-00123" class="html-bibr">43</a>]. Panel (<b>B</b>) reproduced with permission from American Institute of Physics Publishing. The device in panel (<b>A</b>) contains worm loading and washing channels (on the right) and an outlet for collecting injected worms. Worm is immobilized in the middle region for injection. The image frames in panel (<b>B</b>) show a sequence of worm loading, injection, and flushing. Refer to respective references for more details.</p>
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<p>Microfluidic devices for multidirectional orientation and imaging of <span class="html-italic">C. elegans</span> using (<b>A</b>) rotatable glass capillaries (Ardeshiri et al. [<a href="#B54-micromachines-07-00123" class="html-bibr">54</a>] and (<b>B</b>) acoustofluidic rotational manipulation (ARM) (Ahmed et al. [<a href="#B55-micromachines-07-00123" class="html-bibr">55</a>]. Panel (<b>B</b>) reproduced with permission from Adapted by permission from Macmillan Publishers Ltd. Nature Communications. Panel (<b>A</b>) shows an adult worm inside the channel with the region of interest (ROI) in the middle. The worm is held by the negative pressure in the glass capillary. The two sets of brightfield and fluorescent images below show pre- and post-rotated views of specific neuronal processes (VC). Schematic view of the ARM device (<b>B</b>). It contains a piezoelectric transducer to generate acoustic waves. Air bubbles within sidewall cavities cause worms to rotate. The image below shows a mid-L4 worm trapped by oscillating bubbles. Refer to respective references for device details.</p>
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<p>Microfluidic devices to investigate <span class="html-italic">C. elegans</span> behavior in response to (<b>A</b>) chemicals and heat (McCormick et al. [<a href="#B59-micromachines-07-00123" class="html-bibr">59</a>]); (<b>B</b>) chemical gradients (schematic drawing of the device used by Hu et al. [<a href="#B60-micromachines-07-00123" class="html-bibr">60</a>]); and (<b>C</b>) electric field (Rezai et al. [<a href="#B9-micromachines-07-00123" class="html-bibr">9</a>]). Panel (<b>C</b>) reproduced with permissions from the Royal Society of Chemistry. Panel (<b>A</b>) shows head swinging of the worm in response to chemical exposure. In panel (<b>B</b>), the circular channel pattern used to generate the chemical gradient is shown. Worms enter into channels 1–8, which are 300 μm wide, 80 μm high, and 10 μm long depending upon their attractive responses to the NaCl gradient. The electrotaxis device in panel (<b>C</b>) contains electrodes to apply a DC electric field and a long channel for worm swimming. Refer to respective references for more details.</p>
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<p>Microfluidic devices to investigate <span class="html-italic">C. elegans</span> (<b>A</b>) egg-laying (Li et al. [<a href="#B83-micromachines-07-00123" class="html-bibr">83</a>]) and (<b>B</b>) development (Wen et al. [<a href="#B30-micromachines-07-00123" class="html-bibr">30</a>]), by isolating worms inside microchambers with renewable chemical environment. Reproduced with permission from the Royal Society of Chemistry. The left-hand diagram in panel (<b>A</b>) shows eight chambers on each side (one of which is enlarged on the right). Inlets are used to load worms and outlets for bacterial flow. The middle counting region (2 mm × 2 mm), indicated by the red rectangle, is monitored by camera. Panel (<b>B</b>) shows the droplet chip. Schematics of worm encapsulation and substrate exchange in each droplet are shown in three steps on the right side. The amount of substrate exchange is indicated by the color change. Refer to respective references for more details.</p>
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<p>Microfluidic devices for neuromuscular electrophysiological studies on <span class="html-italic">C. elegans</span> (Lockery et al. and Hu et al. [<a href="#B92-micromachines-07-00123" class="html-bibr">92</a>,<a href="#B94-micromachines-07-00123" class="html-bibr">94</a>]). Panel (<b>A</b>) reproduced with permission from the Royal Society of Chemistry. The EPG recording device (panel (<b>A</b>)) contains a worm channel and a funnel-shaped trap region. Fluid flows through the side-arm channel. Panel (<b>B</b>) shows the neurochip. Blue indicates the layer containing the microfluidic region (for worms and chemicals) and white shows the pneumatic control layer. The red circle contains the trapped worm’s head. The red square contains micropillars to correctly orient the worm. V1–4 are valves and the solid black squares are microelectrodes. Refer to respective references for more details.</p>
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<p>A microfluidic device for (<b>A</b>) laser nanoaxotomy of the ALM neuron in <span class="html-italic">C. elegans</span> and (<b>B</b>) investigation of time-lapse nerve regeneration (Guo et al. [<a href="#B97-micromachines-07-00123" class="html-bibr">97</a>]). Reproduced with permission from Adapted by permission from Macmillan Publishers Ltd. Nature Methods. On the left (<b>A-i</b>) the trap system (<b>yellow</b> rectangle) and the three recovery chambers (<b>blue</b> rectangle) are indicated. The right panel (<b>A-ii</b>) shows a magnified view of the trapping system. The small yellow dotted rectangles show four valves to control worms. Panels (<b>B-i to B-iv</b>) show axonal recovery. Branching is visible several minutes after axotomy. By 70 min the nerve has regrown and appears to be reconnected. Refer to the references for more details.</p>
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1933 KiB  
Article
High-Throughput Assessment of Drug Cardiac Safety Using a High-Speed Impedance Detection Technology-Based Heart-on-a-Chip
by Xi Zhang, Tianxing Wang, Ping Wang and Ning Hu
Micromachines 2016, 7(7), 122; https://doi.org/10.3390/mi7070122 - 19 Jul 2016
Cited by 42 | Viewed by 6808
Abstract
Drug cardiac safety assessments play a significant role in drug discovery. Drug-induced cardiotoxicity is one of the main reasons for drug attrition, even when antiarrhythmic drugs can otherwise effectively treat the arrhythmias. Consequently, efficient drug preclinical assessments are needed in the drug industry. [...] Read more.
Drug cardiac safety assessments play a significant role in drug discovery. Drug-induced cardiotoxicity is one of the main reasons for drug attrition, even when antiarrhythmic drugs can otherwise effectively treat the arrhythmias. Consequently, efficient drug preclinical assessments are needed in the drug industry. However, most drug efficacy assessments are performed based on electrophysiological tests of cardiomyocytes in vitro and cannot effectively provide information on drug-induced dysfunction of cardiomyocyte beating. Here we present a heart-on-a-chip device for evaluating the drug cardiac efficacy using a high-speed impedance detection technology. Verapamil and doxorubicin were utilized to test this heart-on-a-chip, and multiple parameters of cardiomyocyte beating status are used to reveal the effects of drugs. The results show that drug efficacy or cardiotoxicity can be determined by this heart-on-a-chip. We believe this heart-on-a-chip will be a promising tool for the preclinical assessment of drug cardiac efficacy. Full article
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<p>Establishment of heart-on-a-chip for drug assessment. (<b>a</b>) The fabrication of interdigitated electrodes (IDEs); (<b>b</b>) The IDEs layout and image of device; (<b>c</b>) Schematics of heart-on-a-chip with IDEs and impedance detection method; (<b>d</b>) The Diff-Quik staining images of cardiomyocytes on the device; (<b>e</b>) High-throughput impedance detection system for drug assessment using beating characteristics.</p>
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<p>Heart-on-a-chip for verapamil test. (<b>a</b>) The beating signals before and after the verapamil with different concentrations are administered on the cardiomyocytes; (<b>b</b>) Statistical beating rate within 60 min in the presence of verapamil; (<b>c</b>) Statistical beating rate within 60 min in the presence of verapamil.</p>
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<p>Heart-on-a-chip for doxorubicin test. (<b>a</b>) The beating signals before and after the doxorubicin with different concentrations are administered on the cardiomyocytes; (<b>b</b>) Statistical beating rate within 60 min in the presence of doxorubicin; (<b>c</b>) Statistical beating rate within 60 min in the presence of doxorubicin.</p>
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<p>Cell viability test by the impedance detection method. (<b>a</b>) Cell growth curves in the absence and presence of verapamil; (<b>b</b>) Cell growth curves in the absence and presence of doxorubicin. Black arrows show the initial time of drug treatment.</p>
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<p>Long-term monitoring (24 h) after drug treatment.</p>
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8270 KiB  
Article
Cytostretch, an Organ-on-Chip Platform
by Nikolas Gaio, Berend Van Meer, William Quirós Solano, Lambert Bergers, Anja Van de Stolpe, Christine Mummery, Pasqualina M. Sarro and Ronald Dekker
Micromachines 2016, 7(7), 120; https://doi.org/10.3390/mi7070120 - 14 Jul 2016
Cited by 37 | Viewed by 8398
Abstract
Organ-on-Chips (OOCs) are micro-fabricated devices which are used to culture cells in order to mimic functional units of human organs. The devices are designed to simulate the physiological environment of tissues in vivo. Cells in some types of OOCs can be stimulated in [...] Read more.
Organ-on-Chips (OOCs) are micro-fabricated devices which are used to culture cells in order to mimic functional units of human organs. The devices are designed to simulate the physiological environment of tissues in vivo. Cells in some types of OOCs can be stimulated in situ by electrical and/or mechanical actuators. These actuations can mimic physiological conditions in real tissue and may include fluid or air flow, or cyclic stretch and strain as they occur in the lung and heart. These conditions similarly affect cultured cells and may influence their ability to respond appropriately to physiological or pathological stimuli. To date, most focus has been on devices specifically designed to culture just one functional unit of a specific organ: lung alveoli, kidney nephrons or blood vessels, for example. In contrast, the modular Cytostretch membrane platform described here allows OOCs to be customized to different OOC applications. The platform utilizes silicon-based micro-fabrication techniques that allow low-cost, high-volume manufacturing. We describe the platform concept and its modules developed to date. Membrane variants include membranes with (i) through-membrane pores that allow biological signaling molecules to pass between two different tissue compartments; (ii) a stretchable micro-electrode array for electrical monitoring and stimulation; (iii) micro-patterning to promote cell alignment; and (iv) strain gauges to measure changes in substrate stress. This paper presents the fabrication and the proof of functionality for each module of the Cytostretch membrane. The assessment of each additional module demonstrate that a wide range of OOCs can be achieved. Full article
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<p>(<b>a</b>) Back view of the 3D sketch of the Cytostretch; (<b>b</b>) Example of a 3D-printed holder for the Cytostretch, including a cell culture chamber on top of the die and a pumping system to inflate the membrane; (<b>c</b>) Top view of the device mounted in the holder.</p>
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<p>(<b>a</b>) Cytostretch (with MEA module embedded) at relaxed state; (<b>b</b>) The Cytostretch device during inflation by applying an air pressure of 10 kPa on the back of the membrane.</p>
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<p>Process flow for the product platform: (<b>a</b>) Si wafer; (<b>b</b>) PECVD SiO<sub>2</sub> deposition; (<b>c</b>) Back SiO<sub>2</sub> patterning; (<b>d</b>) PDMS deposition; (<b>e</b>) DRIE Si etching; (<b>f</b>) Wet SiO<sub>2</sub> etching. Figures are not to scale.</p>
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<p>Process flow for the through-membrane micro-pore array: (<b>a</b>) Al sputtering; (<b>b</b>) PR spinning and patterning; (<b>c</b>) Al patterning; (<b>d</b>) PDMS patterning; (<b>e</b>) Membrane releasing. Figures are not to scale.</p>
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<p>Schematic of setup for simple migration experiment.</p>
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<p>SEM images of microporous PDMS membranes: (<b>a</b>) 15-µm-thick membrane with through-membrane pores 8 µm in diameter; (<b>b</b>) 9-µm-thick membrane with through-membrane pores 14 µm in diameter.</p>
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<p>Phase contrast images of migration experiment. (<b>a</b>) The top of the micro-porous membrane 5 min after seeding shows immune cells resting on pores; (<b>b</b>) The volume below the membrane 3.5 h after seeding shows immune cells floating.</p>
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<p>Process flow for the MEA module: (<b>a</b>) Substrate; (<b>b</b>) Al deposition and patterning; (<b>c</b>) First layer of polyimide (or, alternatively, parylene) is spun and patterned; (<b>d</b>) TiN deposition and patterning; (<b>e</b>) Second layer of polyimide (or, alternatively, parylene) is spun and patterned; (<b>f</b>) PDMS deposition; (<b>g</b>) PDMS patterning; (<b>h</b>) Membrane releasing. Figures are not to scale.</p>
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<p>(<b>a</b>) SEM image of the Cytostretch chip from the back; (<b>b</b>) Close-up of the area highlighted in (<b>a</b>) depicting transversal micro-grooves, the exposed TiN electrodes and parylene insulation of the metal tracks. Adapted from [<a href="#B25-micromachines-07-00120" class="html-bibr">25</a>].</p>
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<p>(<b>a</b>) Optical images of cardiac induced pluripotent stem cell (iPSC) on the Cytostretch device; (<b>b</b>) The field potential recording from one of the electrodes.</p>
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<p>Process flow for the micro-groove module: (<b>a</b>) Substrate with Ti mask embedded in the front-side SiO<sub>2</sub> layer; (<b>b</b>) PR spinning and patterning; (<b>c</b>) PDMS patterning; (<b>d</b>) Membrane releasing; (<b>e</b>) PR stripping. Figures are not to scale.</p>
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<p>Confocal images of hPSC-CMs stained for anti-alpha-actinin (red) and DAPI (blue) to reveal the sarcomeric structure and cell nucleus. (<b>a</b>) hPSC-CM on plain PDMS; (<b>b</b>,<b>c</b>) hPSC-CM on micro-patterned PDMS.</p>
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<p>Process flow for the strain gauges: (<b>a</b>) Ti deposition and patterning; (<b>b</b>) Al deposition; (<b>c</b>) membrane releasing and Al etching. The figures are not to scale.</p>
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<p>Measurement setup (<b>a</b>) and custom-made holder (<b>b</b>) used to measure the resistance change of the Ti strain gauges in the Cytostretch membrane platform.</p>
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<p>(<b>a</b>) Optical image from the front side showing a close-up of the Ti gauges at the interface between the silicon substrate and the PDMS membrane. As presented in [<a href="#B33-micromachines-07-00120" class="html-bibr">33</a>], the strain gauges were fabricated on circular membranes; (<b>b</b>) Relative resistance change of a strain gauge (primary <span class="html-italic">Y</span> axis) and the average strain on the membrane (secondary <span class="html-italic">Y</span>-axis) as function of pressure.</p>
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Article
Combining Electro-Osmotic Flow and FTA® Paper for DNA Analysis on Microfluidic Devices
by Ryan Wimbles, Louise M. Melling and Kirsty J. Shaw
Micromachines 2016, 7(7), 119; https://doi.org/10.3390/mi7070119 - 14 Jul 2016
Cited by 7 | Viewed by 5331
Abstract
FTA® paper can be used to protect a variety of biological samples prior to analysis, facilitating ease-of-transport to laboratories or long-term archive storage. The use of FTA® paper as a solid phase eradicates the need to elute the nucleic acids from [...] Read more.
FTA® paper can be used to protect a variety of biological samples prior to analysis, facilitating ease-of-transport to laboratories or long-term archive storage. The use of FTA® paper as a solid phase eradicates the need to elute the nucleic acids from the matrix prior to DNA amplification, enabling both DNA purification and polymerase chain reaction (PCR)-based DNA amplification to be performed in a single chamber on the microfluidic device. A disc of FTA® paper, containing a biological sample, was placed within the microfluidic device on top of wax-encapsulated DNA amplification reagents. The disc containing the biological sample was then cleaned up using Tris-EDTA (TE) buffer, which was passed over the disc, via electro-osmotic flow, in order to remove any potential inhibitors of downstream processes. DNA amplification was successfully performed (from buccal cells, whole blood and semen) using a Peltier thermal cycling system, whereupon the stored PCR reagents were released during the initial denaturing step due to the wax barrier melting between the FTA® disc and PCR reagents. Such a system offers advantages in terms of a simple sample introduction interface and the ability to process archived samples in an integrated microfluidic environment with minimal risk of contamination. Full article
(This article belongs to the Special Issue Application of Microfluidic Methodology for the Analysis of DNA)
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<p>(<b>a</b>) Photograph showing the design of the microfluidic device used to perform integrated DNA purification and amplification experiments. The buffer wells are connected to the central chamber via 250-µm channels; (<b>b</b>) Schematic top-view showing the location of the channels, central chamber and reservoirs at the end of each channel. The dashed red line also indicates the cross-section view though which (<b>c</b>) occurs; (<b>c</b>) Schematic cross-section showing how the FTA<sup>®</sup> paper discs are placed in the central chamber on top of a layer of wax-encapsulated PCR reagents.</p>
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<p>Graph showing the EOF velocity of the TE buffer used in the DNA purification process. Error bars represent the standard deviation of the triplicate analysis performed on three separate microfluidic devices.</p>
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<p>PCR product intensity compared to the voltage applied during the purification procedure on the microfluidic device (<span class="html-italic">n</span> = 3). Peak area refers to the band intensity/peak area of the PCR products on the gel. Conventional off-chip positive and negative controls produced peak areas of 4768 (±780) and 93 (±93), respectively. Error bars represent the standard deviation from triplicate analysis.</p>
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<p>Results from direct analysis of semen samples on FTA<sup>®</sup> paper using a variety of treatment conditions for disulphide bond reduction (<span class="html-italic">n</span> = 3). A range of treatment options were tested: (1) semen added to FTA<sup>®</sup> paper and dried; (2) semen added to FTA<sup>®</sup> paper, dried, 40 µL of 1 M DTT added and dried; (3) semen and 1 M DTT mixed 50:50 (<span class="html-italic">v</span>/<span class="html-italic">v</span>), added to FTA<sup>®</sup> paper and dried; (4) 40 µL of 1 M DTT added to FTA<sup>®</sup> paper, dried, semen added and dried. Error bars represent the standard deviation from triplicate analysis.</p>
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18878 KiB  
Review
Plasmonic Structures, Materials and Lenses for Optical Lithography beyond the Diffraction Limit: A Review
by Changtao Wang, Wei Zhang, Zeyu Zhao, Yanqin Wang, Ping Gao, Yunfei Luo and Xiangang Luo
Micromachines 2016, 7(7), 118; https://doi.org/10.3390/mi7070118 - 13 Jul 2016
Cited by 50 | Viewed by 11955
Abstract
The rapid development of nanotechnologies and sciences has led to the great demand for novel lithography methods allowing large area, low cost and high resolution nano fabrications. Characterized by unique sub-diffraction optical features like propagation with an ultra-short wavelength and great field enhancement [...] Read more.
The rapid development of nanotechnologies and sciences has led to the great demand for novel lithography methods allowing large area, low cost and high resolution nano fabrications. Characterized by unique sub-diffraction optical features like propagation with an ultra-short wavelength and great field enhancement in subwavelength regions, surface plasmon polaritons (SPPs), including surface plasmon waves, bulk plasmon polaritons (BPPs) and localized surface plasmons (LSPs), have become potentially promising candidates for nano lithography. In this paper, investigations into plasmonic lithography in the manner of point-to-point writing, interference and imaging were reviewed in detail. Theoretical simulations and experiments have demonstrated plasmonic lithography resolution far beyond the conventional diffraction limit, even with ultraviolet light sources and single exposure performances. Half-pitch resolution as high as 22 nm (~1/17 light wavelength) was observed in plasmonic lens imaging lithography. Moreover, not only the overview of state-of-the-art results, but also the physics behind them and future research suggestions are discussed as well. Full article
(This article belongs to the Special Issue Micro/Nano Photonic Devices and Systems)
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<p>(<b>a</b>) SPPs (surface plasmon polaritons) on a dielectric–metal interface (<span class="html-italic">H</span> is in the <span class="html-italic">y</span> direction); (<b>b</b>) Field distribution of SPPs in the dielectric and metal material, <span class="html-italic">δ<sub>d</sub></span> and <span class="html-italic">δ<sub>m</sub></span> is the decay length of the field in the dielectric and metal material, respectively; (<b>c</b>) Dispersion curve for an SPP mode. Reproduced from [<a href="#B29-micromachines-07-00118" class="html-bibr">29</a>]. Copyright © 2003, NPG.</p>
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<p>Schematic structure of metal–insulator–metal or insulator–metal–insulator (MIM or IMI) with <span class="html-italic">d</span> the thick core layer. The core layer and claddings are represented by Roman numbers “I” and “II”, respectively. The odd and even modes are represented by the orange-colored curve, respectively.</p>
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<p>Typical configurations for SPPs excitation. (<b>a</b>) Kretschmann prism geometry, (<b>b</b>) Two-layer Kretschmann prism geometry; (<b>c</b>) Otto prism geometry; (<b>d</b>) Excitation with an SNOM probe; (<b>e</b>) Excitation by a grating, and (<b>f</b>) Excitation by surface features. Reproduced from [<a href="#B33-micromachines-07-00118" class="html-bibr">33</a>]. Copyright © 2004, Elsevier.</p>
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<p>(<b>a</b>) Schematic of BPPs (plasmon polaritons) in hyperbolic metamaterial with alternative stacked metal–dielectric nano films; (<b>b</b>) Dispersion relation of the multilayer films with different signs of <span class="html-italic">ε<sub>x</sub></span> and <span class="html-italic">ε<sub>z</sub></span>. Reproduced from [<a href="#B34-micromachines-07-00118" class="html-bibr">34</a>]. Copyright © 2014, AIP.</p>
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<p>Hyperbolic equal-frequency contour (EFC) surface for metamaterial with (<b>a</b>) <span class="html-italic">ε<sub>z</sub></span> &gt; 0, <span class="html-italic">ε<sub>x</sub></span> &gt; 0; and (<b>b</b>) <span class="html-italic">ε<sub>z</sub></span> &gt; 0, <span class="html-italic">ε<sub>x</sub></span> &lt; 0. The group velocity is indicated by the arrows, which are perpendicular to the EFC.</p>
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<p>(<b>a</b>) Top panel is the calculation of optical transmission function (OTF) for SiO<sub>2</sub>/Al films with variant thickness by RCWA and EMT. Middle and bottom panels are the real and imaginary part of <span class="html-italic">k<sub>z</sub></span> for variant <span class="html-italic">k<sub>x</sub></span> calculated by Bloch theorem without considering the Al absorption. OTF plots in logarithm scale as function of (<b>b</b>) unit thickness <span class="html-italic">d</span> and (<b>c</b>) metal film filling factor <span class="html-italic">f</span>. Reproduced from [<a href="#B37-micromachines-07-00118" class="html-bibr">37</a>]. Copyright © 2015, WILEY.</p>
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<p>(<b>a</b>) Schematic structure of grating excited SPPs’ interference lithography; (<b>b</b>) Simulated electric field intensity distribution; (<b>c</b>) Resist recording results of SPPs’ interference fringes. Reproduced from [<a href="#B21-micromachines-07-00118" class="html-bibr">21</a>], Copyright © 2004, AIP.</p>
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<p>(<b>a</b>) Schematic configuration of SPPs’ interference lithography with two parallel gratings; (<b>b</b>) Cross sections of electrical field |<span class="html-italic">E</span>| distribution in (a); (<b>c</b>) Schematic experimental configuration of SPPs interference lithography; (<b>d</b>) Exposure pattern of structure (c); (<b>e</b>) SPPs’ interference through prism excitation; (<b>f</b>) Atomic force microscopy (AFM) image of one-dimensional interference patterns by prism. Reproduced from: (a,b), [<a href="#B49-micromachines-07-00118" class="html-bibr">49</a>], Copyright © 2005, ACS; (c,d), [<a href="#B50-micromachines-07-00118" class="html-bibr">50</a>], Copyright © 2009, ACS; (e,f) [<a href="#B52-micromachines-07-00118" class="html-bibr">52</a>], Copyright © 2010, OAS.</p>
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<p>(<b>a</b>) Schematic structure of the odd SPP mode interference lithography; Simulation results at the wavelength of (<b>b</b>) 442 nm and (<b>c</b>) 193 nm; (<b>d</b>) Experimental structure for the odd SPP mode interference lithography; (<b>e</b>) Top view and (<b>f</b>) Cross section of SEM pictures of 100 nm-thick photoresist. Reproduced from: (b), [<a href="#B55-micromachines-07-00118" class="html-bibr">55</a>], Copyright © 2009, Springer; (a,c), [<a href="#B56-micromachines-07-00118" class="html-bibr">56</a>], Copyright © 2014, NPG; (d–f), [<a href="#B57-micromachines-07-00118" class="html-bibr">57</a>], Copyright © 2016, ACS.</p>
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<p>(<b>a</b>) Schematic configuration of two-BPPs’ interference; (<b>b</b>) SEM image of exposure photoresist; (<b>c</b>) Schematic configuration of four-BPPs’ interference; (<b>d</b>) AFM image of two-dimension interference pattern. Feature size of results is 45 nm. Reproduced from [<a href="#B37-micromachines-07-00118" class="html-bibr">37</a>], Copyright © 2015, WILEY.</p>
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<p>(<b>a</b>) Schematic structure of two-SPPs absorption interference lithography; (<b>b</b>) Simulated interference intensity distribution; (<b>c</b>) Experimental results of resist pattern. Reproduced from [<a href="#B60-micromachines-07-00118" class="html-bibr">60</a>], Copyright © 2013, AIP.</p>
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<p>Various nanostructures used to confine SPPs and achieve a nano-scale spot. (<b>a</b>) Zoom in SEM picture of the bowtie aperture; (<b>b</b>) 100 nm aperture on the NSOM tip after the fabrication of the plasmonic lens; (<b>c</b>) Modified bowtie aperture with full circular grooves on the exit side of the film. Reproduced from: (a), [<a href="#B28-micromachines-07-00118" class="html-bibr">28</a>], Copyright © 2006, ACS; (b), [<a href="#B67-micromachines-07-00118" class="html-bibr">67</a>], Copyright © 2008, ACS; (c), [<a href="#B68-micromachines-07-00118" class="html-bibr">68</a>], Copyright © 2011, AIP.</p>
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<p>(<b>a</b>) Schematic structure of a circle cut into a 150 nm thick silver film; (<b>b</b>) Near-field pattern recorded by NSOM; (<b>c</b>) Symmetry broken plasmonic corral fabricated on the Au film; (<b>d</b>) |<span class="html-italic">E<sub>z</sub></span>|<sup>2</sup> distributions under linearly polarized lasers; A (<b>e</b>) left- and (<b>f</b>) right-handed spiral plasmonic lens in gold film; (<b>g</b>) Schematic geometry of the semicircular slits on the Au film filled with different medium; (<b>h</b>) A cross section of this structure; (<b>i</b>) A spiral triangle array structure; (<b>j</b>) Alternating spiral triangle array and spiral slot lens. Reproduced from: (a,b), [<a href="#B69-micromachines-07-00118" class="html-bibr">69</a>], Copyright © 2005, ACS; (c,d), [<a href="#B70-micromachines-07-00118" class="html-bibr">70</a>], Copyright © 2011, ACS; (e,f), [<a href="#B71-micromachines-07-00118" class="html-bibr">71</a>], Copyright © 2010, ACS; (g,h), [<a href="#B72-micromachines-07-00118" class="html-bibr">72</a>], Copyright © 2014, Springer; (i,j), [<a href="#B73-micromachines-07-00118" class="html-bibr">73</a>], Copyright © 2012, OSA.</p>
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<p>Nano spot achieved by focusing BPPs of hyperbolic metamaterial. (<b>a</b>) Metalens structure; (<b>b</b>) Simulation result of Metalens; (<b>c</b>) Plasmonic Fresnel plate structure; (<b>d</b>) Simulation result of plasmonic Fresnel plate. Reproduced from: (a,b), [<a href="#B75-micromachines-07-00118" class="html-bibr">75</a>], Copyright © 2010, AIP; (c,d), [<a href="#B76-micromachines-07-00118" class="html-bibr">76</a>], Copyright © 2010, OAS.</p>
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<p>Nano focusing by plasmonic Fano resonance lens. (<b>a</b>) Schematic structure view; (<b>b</b>) transmission spectra; (<b>c</b>) nano focus length with variant focus size. Reproduced from [<a href="#B78-micromachines-07-00118" class="html-bibr">78</a>], Copyright © 2016, RSC.</p>
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<p>(<b>a</b>) SEM picture of circular contact probe with bowtie aperture for plasmonic lithography; (<b>b</b>) AFM image of resist pattern with half pitch 22 nm; (<b>c</b>) SEM picture of plasmonic lens consisting of a dumbbell-shaped aperture, a set of ring couplers (two inner rings) and a ring reflector (the outer ring); (<b>d</b>) Experimental results of resist pattern. Reproduced from: (a,b), [<a href="#B66-micromachines-07-00118" class="html-bibr">66</a>], Copyright © 2012, WILEY; (c,d), [<a href="#B79-micromachines-07-00118" class="html-bibr">79</a>], Copyright © 2011, NGP.</p>
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<p>(<b>a</b>) Schematic structure of plasmonic lithography with bowtie aperture and plasmonic cavity lens resist recording structure; Simulation results (<b>b</b>) with cavity lens and (<b>c</b>) without cavity lens. Reproduced from [<a href="#B80-micromachines-07-00118" class="html-bibr">80</a>], Copyright © 2015, Springer.</p>
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<p>(<b>a</b>) Apertureless tip optical nanolithography; Scanning probe nanolithography based on (<b>b</b>) thermo and (<b>c</b>) chemical reactions. Reproduced from: (a), [<a href="#B81-micromachines-07-00118" class="html-bibr">81</a>], Copyright © 2002, AIP; (b), [<a href="#B83-micromachines-07-00118" class="html-bibr">83</a>], Copyright © 2010, AAAS; (c), [<a href="#B84-micromachines-07-00118" class="html-bibr">84</a>], Copyright © 2014, NGP.</p>
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<p>Schematic of nanolithography with (<b>a</b>) tip–insulator–metal and (<b>b</b>) tip–insulator structures; Simulated electric field intensity distribution of (<b>c</b>) tip–insulator–metal and (<b>d</b>) tip–insulator structures. Reproduced from [<a href="#B85-micromachines-07-00118" class="html-bibr">85</a>], Copyright © 2013, Springer.</p>
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<p>(<b>a</b>) Local plasmonic lithography system with a contact probe on a metal spring; (<b>b</b>) Schematic view of metal spring; (<b>c</b>) Cross-section schematic of the plasmonic head flying above the high-speed rotating substrate; (<b>d</b>) Schematic diagram of the nanolithography setup with ISPI gratings; (<b>e</b>) Schematic of the plasmonic optical head. Reproduced from (a), [<a href="#B86-micromachines-07-00118" class="html-bibr">86</a>], Copyright © 2009, OSA; (b), [<a href="#B66-micromachines-07-00118" class="html-bibr">66</a>], Copyright © 2012, WILEY; (c), [<a href="#B27-micromachines-07-00118" class="html-bibr">27</a>], Copyright © 2008, NPG; (d), [<a href="#B87-micromachines-07-00118" class="html-bibr">87</a>], Copyright © 2014, Springer; (e), [<a href="#B88-micromachines-07-00118" class="html-bibr">88</a>], Copyright © 2012, AIP.</p>
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<p>Imaging principle of (<b>a</b>) perfect lens and (<b>b</b>) superlens. Reproduced from [<a href="#B18-micromachines-07-00118" class="html-bibr">18</a>]. Copyright © 2000, APS.</p>
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<p>Schematic structures of variant hyperlenses with metal-dielectric films in (<b>a</b>) circular cylinder; (<b>b</b>) spherical form; (<b>c</b>) complex transformed coordinates. Reproduced from: (a), [<a href="#B91-micromachines-07-00118" class="html-bibr">91</a>], Copyright © 2006, OAS; (b), [<a href="#B92-micromachines-07-00118" class="html-bibr">92</a>], Copyright © 2010, NPG; (c), [<a href="#B93-micromachines-07-00118" class="html-bibr">93</a>], Copyright © 2008, ACS.</p>
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<p>Optical bulk negative refraction index lens by (<b>a</b>) Silver nanowire metamaterials and (<b>b</b>) Stacked plasmonic waveguides metamaterial. Reproduced from: (a), [<a href="#B99-micromachines-07-00118" class="html-bibr">99</a>], Copyright © 2008, AAAS; (b), [<a href="#B39-micromachines-07-00118" class="html-bibr">39</a>], Copyright © 2013, NPG.</p>
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<p>(<b>a</b>) Schematic of Ag superlens for plasmonic imaging lithography; (<b>b</b>) AFM image for 60 nm half-pitch feature through Ag superlens (scale bar, 1 mm); (<b>c</b>) The ‘‘NANO’’ object on the Cr film; AFM of the developed image on photoresist (<b>d</b>) with or (<b>e</b>) without a Ag superlens; (<b>f</b>) Cross section of letter ‘‘A’’ in (d,e), Scale bar in (c–e) is 2 mm. Reproduced from [<a href="#B22-micromachines-07-00118" class="html-bibr">22</a>], Copyright © 2005, AAAS.</p>
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<p>(<b>a</b>,<b>b</b>) are the schematic structures of a superlens; AFM image of resist pattern with half-pitch (<b>c</b>) 30 nm and (<b>b</b>) 60 nm. Reproduced from: (a,c) [<a href="#B101-micromachines-07-00118" class="html-bibr">101</a>], Copyright © 2010, AIP; (b,d) [<a href="#B103-micromachines-07-00118" class="html-bibr">103</a>], Copyright © 2012, ACS.</p>
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<p>(<b>a</b>) Schematic structure of plasmonic reflective lens lithography; Image intensity distribution (<b>b</b>) without reflection and (<b>c</b>) with reflection. The longitudinal profile distribution of <span class="html-italic">I</span><sub>0</sub> and <span class="html-italic">I</span><sub>1</sub> in (b,c) are shown in (<b>d</b>,<b>e</b>). Reproduced from: [<a href="#B111-micromachines-07-00118" class="html-bibr">111</a>], Copyright © 2007, OAS.</p>
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<p>(<b>a</b>) Schematic structure of plasmonic reflective lens lithography; (<b>b</b>,<b>d</b>) Plasmonic reflective lens lithography imaging and (<b>c,</b><b>e</b>) conventional near-field imaging lithography. Feature size of the pattern is approximately 50 nm. (<b>f</b>) SEM picture of 32 nm half-pitch pattern for reflective plasmonic lens lithography. Reproduced from: [<a href="#B23-micromachines-07-00118" class="html-bibr">23</a>], Copyright © 2013, OAS.</p>
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<p>(<b>a</b>) Schematic structure of plasmonic cavity lens lithography; (<b>b</b>) H-field amplitude at the interface of the Ag superlens and photoresist as a function of the optical wavelength and the transverse wavevector through the plasmonic cavity lens structure, inset is the approximately mirror-symmetric distribution of surface charges; Simulation results of the object with (<b>c</b>,<b>d</b>) 62 nm and (<b>e</b>,<b>f</b>) 45 nm resolution. Reproduced from: (a–d), [<a href="#B55-micromachines-07-00118" class="html-bibr">55</a>], Copyright © 2009, Springer; (e,f), [<a href="#B112-micromachines-07-00118" class="html-bibr">112</a>], Copyright © 2013, OSA.</p>
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<p>(<b>a</b>,<b>b</b>) are the scanning electron microscope (SEM) pictures and cross profile of the resist pattern for half-pitch 32 nm, respectively; (<b>c</b>,<b>d</b>) are for half-pitch 22 nm. Inset in (c) is Fourier spectrum distribution. Reproduced from [<a href="#B24-micromachines-07-00118" class="html-bibr">24</a>], Copyright © 2015, AIP.</p>
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<p>(<b>a</b>) Schematic structure of plasmonic lithography incorporating PSM; (<b>b</b>,<b>c</b>) Principle of plasmonic PSM; Simulation results of 30 nm resolution pattern (<b>d</b>) with PSM and (<b>e</b>) without PSM. Reproduced from [<a href="#B113-micromachines-07-00118" class="html-bibr">113</a>], Copyright © 2011, OSA.</p>
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<p>(<b>a</b>) Schematic structure of SPPs cavity lens imaging under off-axis illumination (OAI); Imaging contrast of dense line pattern as a function of air working distance and feature size in the case of (<b>b</b>) conventional near-field imaging and (<b>c</b>) plasmonic cavity lens with OAI (illumination light <span class="html-italic">k<sub>x</sub></span><sub>,inc</sub> = 1.5<span class="html-italic">k</span><sub>0</sub>); (<b>d</b>) Schematic structure of planar hyperlens imaging under OAI; (<b>e</b>,<b>f</b>) are the simulation results of the structure in (d) under normal and off-axis illumination, respectively; (<b>g</b>) Schematic structure of plasmonic cavity lens imaging under surface plasmon illumination (SPI); (<b>h</b>,<b>i</b>) are simulated imaging results of the L-shape feature under normal and off-axis illumination, respectively. The air working distance in (e,f,h,i) is 40 nm. Reproduced from: (a–c), [<a href="#B25-micromachines-07-00118" class="html-bibr">25</a>], Copyright © 2015, NGP; (d–f), [<a href="#B114-micromachines-07-00118" class="html-bibr">114</a>], Copyright © 2014, Springer; (g–i), [<a href="#B115-micromachines-07-00118" class="html-bibr">115</a>], Copyright © 2015, Springer.</p>
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<p>SEM picture of (<b>a</b>) 60 nm resolution with 120 nm air working distance under <span class="html-italic">k<sub>x</sub></span><sub>,inc</sub> = 1.5<span class="html-italic">k</span><sub>0</sub>, (<b>b</b>) 50 nm resolution with 50 nm air working distance under <span class="html-italic">k<sub>x</sub></span><sub>,inc</sub> = 1.5<span class="html-italic">k</span><sub>0</sub>, (<b>c</b>) 45 nm resolution with 20nm air working distance under <span class="html-italic">k<sub>x</sub></span><sub>,inc</sub> = 1.5<span class="html-italic">k</span><sub>0</sub>, (<b>d</b>) 32 nm resolution with 40 nm air working distance under <span class="html-italic">k<sub>x</sub></span><sub>,inc</sub> = 2.5<span class="html-italic">k</span><sub>0</sub>. Reproduced from [<a href="#B25-micromachines-07-00118" class="html-bibr">25</a>], Copyright © 2015, NGP.</p>
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<p>(<b>a</b>) Schematic of pattern on mask; (<b>b</b>) Optical proximity corrected mask design; Simulation results (<b>c</b>) before OPC and (<b>d</b>) after OPC. Reproduced from [<a href="#B23-micromachines-07-00118" class="html-bibr">23</a>], Copyright © 2013, OSA.</p>
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<p>(<b>a</b>) Schematic diagram of the resist pattern transfer for plasmonic lithography. SEM pictures of half-pitch 32 nm bottom layer resist pattern (<b>b</b>) top view and (<b>c</b>) cross sectional view. Scale bar in (b,c), 100 nm. Reproduced from [<a href="#B24-micromachines-07-00118" class="html-bibr">24</a>], Copyright © 2015, AIP.</p>
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<p>SEM pictures of plasmonic lithography for nanostructure employed in (<b>a</b>) integrated circuit, (<b>b</b>) nanofocusing optical lens based on metasurface, (<b>c</b>) surface plasmon polaritons couplers, (<b>d</b>) data recording circuit. Feature size of patterns ranges from 30 to 60 nm. Reproduced from [<a href="#B117-micromachines-07-00118" class="html-bibr">117</a>], Copyright © 2015, AIP.</p>
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14556 KiB  
Article
Synthesis and Electro-Magneto-Mechanical Properties of Graphene Aerogels Functionalized with Co-Fe-P Amorphous Alloys
by Guang-Ping Zheng, Xi Lu and Zhuo Han
Micromachines 2016, 7(7), 117; https://doi.org/10.3390/mi7070117 - 12 Jul 2016
Cited by 6 | Viewed by 4790
Abstract
Graphene aerogels (GAs) are functionalized with Fe-Co-P alloy using an electro-deposition method. The Fe-Co-P alloy coated on the graphene nanosheets is found to possess an amorphous structure and a nanoporous architecture of GAs. The electro-mechanical properties of GAs are significantly affected by the [...] Read more.
Graphene aerogels (GAs) are functionalized with Fe-Co-P alloy using an electro-deposition method. The Fe-Co-P alloy coated on the graphene nanosheets is found to possess an amorphous structure and a nanoporous architecture of GAs. The electro-mechanical properties of GAs are significantly affected by the Fe-Co-P nanoparticles embedded inside GAs. The electro-mechanical responses of GA/Fe-Co-P nanoporous hybrid structures are sensitive to an applied magnetic field, demonstrating that they are promising for electro-magneto-mechanical applications. The light-weight, high-strength and nanoporous GAs functionalized with Fe-Co-P amorphous alloys are desirable sensors, actuators, and nano-electro-mechanical systems that could be controlled or manipulated by mechanical, electric and magnetic fields. Full article
(This article belongs to the Special Issue Graphene Nano-Electro-Mechanical (NEM) Devices and Applications)
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<p>SEM images of GA (<b>a</b>) and GA/Co-Fe-P (Sample-h14) (<b>b</b>). The inset in (<b>b</b>) shows the typical size and shape of GA and GA/Co-Fe-P samples.</p>
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<p>SEM images of GA/Co-Fe-P samples: (<b>a</b>) Sample-h2; (<b>b</b>) Sample-h4; (<b>c</b>) Sample-h8; (<b>d</b>) Sample-h14.</p>
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<p>XRD patterns of GA and GA/Co-Fe-P samples: (<b>a</b>) Sample-h2, Sample-h4 and Sample-h8; (<b>b</b>) GA, Co-Fe-P foils and Sample-h14.</p>
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<p>Raman spectra of GA and GA/Co-Fe-P samples. I<sub>d</sub>/I<sub>g</sub> is the ratio of intensities of D- and G-bands.</p>
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<p>The relative changes of resistances of GA and GA/Co-Fe-P samples under compressive strains in a loading (from 0 to ε<sub>m</sub>) and un-loading (from ε<sub>m</sub> to 0) cycle. ε<sub>m</sub> denotes the maximum applied strain.</p>
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<p>(<b>a</b>) Magnetic hysteresis loop of the GA/Co-Fe-P sample; (<b>b</b>) The relative changes of resistances of GA/Co-Fe-P samples under compressive strains in a loading (from 0 to ε<sub>m</sub>) and un-loading (after ε<sub>m</sub> to 0) cycle, with and without an applied magnetic field H. ε<sub>m</sub> denotes the maximum applied strain.</p>
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6862 KiB  
Article
Gravity-Based Precise Cell Manipulation System Enhanced by In-Phase Mechanism
by Koji Mizoue, Manh Hao Phan, Chia-Hung Dylan Tsai, Makoto Kaneko, Junsu Kang and Wan Kyun Chung
Micromachines 2016, 7(7), 116; https://doi.org/10.3390/mi7070116 - 9 Jul 2016
Cited by 8 | Viewed by 5389
Abstract
This paper proposes a gravity-based system capable of generating high-resolution pressure for precise cell manipulation or evaluation in a microfluidic channel. While the pressure resolution of conventional pumps for microfluidic applications is usually about hundreds of pascals as the resolution of their feedback [...] Read more.
This paper proposes a gravity-based system capable of generating high-resolution pressure for precise cell manipulation or evaluation in a microfluidic channel. While the pressure resolution of conventional pumps for microfluidic applications is usually about hundreds of pascals as the resolution of their feedback sensors, precise cell manipulation at the pascal level cannot be done. The proposed system successfully achieves a resolution of 100 millipascals using water head pressure with an in-phase noise cancelation mechanism. The in-phase mechanism aims to suppress the noises from ambient vibrations to the system. The proposed pressure system is tested with a microfluidic platform for pressure validation. The experimental results show that the in-phase mechanism effectively reduces the pressure turbulence, and the pressure-driven cell movement matches the theoretical simulations. Preliminary experiments on deformability evaluation with red blood cells under incremental pressures of one pascal are successfully performed. Different deformation patterns are observed from cell to cell under precise pressure control. Full article
(This article belongs to the Special Issue Advances in Microfluidic Devices for Cell Handling and Analysis)
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<p>The conventional pressure system and the proposed system. (<b>a</b>) Feedback-controlled pressure system; (<b>b</b>) The control resolution is limited by sensor resolution. The blue signal is an example of measured pressure by a commercial pressure sensor; (<b>c</b>) Conventional gravity-driven pressure system; (<b>d</b>) The proposed system with in-phase noise cancelation.</p>
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<p>The overview of the experimental system. (<b>a</b>) Microfluidic flow is monitored through a camera while the slider is controlled by the signals from the computer; (<b>b</b>) A photo of the whole setup.</p>
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<p>The idea of in-phase noise cancelation: (<b>a</b>) Without in-phase noise cancelation; (<b>b</b>) With in-phase noise cancelation.</p>
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<p>The motion of a microbead. (<b>a</b>) A microbead motion in the system without in-phase noise cancelation; (<b>b</b>) A microbead motion in the system with in-phase noise cancelation; (<b>c</b>) The tracked microbeads positions with respect to time.</p>
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<p>The frequency spectrum without and with in-phase noise cancelation.</p>
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<p>The frequency spectrum without and with the slider motor power turning on.</p>
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<p>Series of photos of cell position with respect to time under various <math display="inline"> <semantics> <mrow> <mi mathvariant="sans-serif">Δ</mi> <mi>H</mi> </mrow> </semantics> </math>: (<b>a</b>) <math display="inline"> <semantics> <mrow> <mi>Δ</mi> <mi>H</mi> <mo>=</mo> <mn>10</mn> <mo> </mo> <mtext>μm</mtext> </mrow> </semantics> </math>; (<b>b</b>) <math display="inline"> <semantics> <mrow> <mi>Δ</mi> <mi>H</mi> <mo>=</mo> <mn>20</mn> <mo> </mo> <mtext>μm</mtext> </mrow> </semantics> </math>; (<b>c</b>) <math display="inline"> <semantics> <mrow> <mi>Δ</mi> <mi>H</mi> <mo>=</mo> <mn>40</mn> <mo> </mo> <mtext>μm</mtext> </mrow> </semantics> </math>; (<b>d</b>) <math display="inline"> <semantics> <mrow> <mi>Δ</mi> <mi>H</mi> <mo>=</mo> <mn>100</mn> <mo> </mo> <mtext>μm</mtext> </mrow> </semantics> </math>.</p>
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<p>RBC velocity analysis. (<b>a</b>) The tracked cell position with respect to time under different <math display="inline"> <semantics> <mrow> <mtext>Δ</mtext> <mi>H</mi> </mrow> </semantics> </math>; (<b>b</b>) RBC velocity distribution based on tracked results.</p>
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<p>The comparison between theoretical and experimental results: (<b>a</b>) The simulated distribution of flow velocity in the microchannel from a 3-dimensional view; (<b>b</b>) The theoretical RBC velocity is estimated by the average flow velocity over the occupied area of the RBC in a cross-section; (<b>c</b>) Comparisons to the experimental results obtained with the water heads from <math display="inline"> <semantics> <mrow> <mi>Δ</mi> <mi>H</mi> <mo>=</mo> <mn>10</mn> <mo> </mo> <mtext>μm</mtext> </mrow> </semantics> </math> to <math display="inline"> <semantics> <mrow> <mi>Δ</mi> <mi>H</mi> <mo>=</mo> <mn>1000</mn> <mo> </mo> <mtext>μm</mtext> </mrow> </semantics> </math>.</p>
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<p>Applications on precise cell evaluation by pressure increments. (<b>a</b>) Two examples of RBC deformation under different amounts of applied pressures; (<b>b</b>) Tracked insertion length.</p>
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1733 KiB  
Article
A New Method of Fixing High-Aspect-Ratio Microstructures by Gel
by Nan Chen, Xiangyu Chen, Penghui Xiong, Shuangyue Hou, Xiaobo Zhang, Ying Xiong, Gang Liu and Yangchao Tian
Micromachines 2016, 7(7), 115; https://doi.org/10.3390/mi7070115 - 9 Jul 2016
Cited by 3 | Viewed by 5048
Abstract
In the microfabrication processes, it is necessary to examine the quality of the structures to ensure the whole process runs smoothly. However, the examination process of pattern defects is interrupted during the fabrication of high-aspect-ratio microstructures. The inevitable pattern defects arise from capillary [...] Read more.
In the microfabrication processes, it is necessary to examine the quality of the structures to ensure the whole process runs smoothly. However, the examination process of pattern defects is interrupted during the fabrication of high-aspect-ratio microstructures. The inevitable pattern defects arise from capillary forces which occur during the liquid drying process. In this paper, a new method that enables us to fix the microstructures with gel to restrict deformations before the rinsed liquid drying process has been proposed. It is effective to avoid the capillary forces by preventing the formation of the liquid level. The process parameters, types of gel, gel time and observation time were discussed and the flatness and thickness of the gel layer could be controlled. A series of high-aspect-ratio microstructures were fixed in good condition by gel. Full article
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<p>(<b>a</b>) Evaporation of liquid during conventional drying process; (<b>b</b>) Deformation of the microstructures during conventional drying process; (<b>c</b>) The microstructures fixed by gel.</p>
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<p>The processes of fabricating metal microstructures with the new method: (<b>a</b>) Adding the sol and forming gel; (<b>b</b>) Examination of fixing photoresist microstructures under the microscope; (<b>c</b>) Loading the sample on the holder; (<b>d</b>) Dissolving the gel in the warm water; (<b>e</b>) Electroplating process.</p>
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<p>The stereoscopic microscopy images of the gratings (side views): (<b>a</b>) After the conventional drying process, some structures deformed or adhered together (width: 24 μm; height: 240 μm); (<b>b</b>) The structures were fixed by gellan gum gel (width: 24 μm; height: 240 μm); (<b>c</b>) After the liquid drying process, the top of the structures adhered to each other (width: 15 μm; height: 240 μm); (<b>d</b>) The structures were fixed by gellan gum gel (width: 15 μm; height: 240 μm).</p>
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<p>Images of SU-8 beams (width: 20 μm; height: 240 μm). (<b>a</b>) Traditional drying process; (<b>b</b>) Addition of agarose sol before the drying process; (<b>c</b>) Addition of gellan gum sol before the drying process.</p>
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<p>Gellan gum spin speed versus thickness.</p>
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<p>The gel time and observation time versus the concentration of the gellan gum sol.</p>
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<p>The optical microscopy images of the micro-gratings (width: 20 μm; height: 240 μm): (<b>a</b>) Within observation time; (<b>b</b>) 10 min later.</p>
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7860 KiB  
Article
A Microchip for High-Throughput Axon Growth Drug Screening
by Hyun Soo Kim, Sehoon Jeong, Chiwan Koo, Arum Han and Jaewon Park
Micromachines 2016, 7(7), 114; https://doi.org/10.3390/mi7070114 - 7 Jul 2016
Cited by 14 | Viewed by 8042
Abstract
It has been recently known that not only the presence of inhibitory molecules associated with myelin but also the reduced growth capability of the axons limit mature central nervous system (CNS) axonal regeneration after injury. Conventional axon growth studies are typically conducted using [...] Read more.
It has been recently known that not only the presence of inhibitory molecules associated with myelin but also the reduced growth capability of the axons limit mature central nervous system (CNS) axonal regeneration after injury. Conventional axon growth studies are typically conducted using multi-well cell culture plates that are very difficult to use for investigating localized effects of drugs and limited to low throughput. Unfortunately, there is currently no other in vitro tool that allows investigating localized axonal responses to biomolecules in high-throughput for screening potential drugs that might promote axonal growth. We have developed a compartmentalized neuron culture platform enabling localized biomolecular treatments in parallel to axons that are physically and fluidically isolated from their neuronal somata. The 24 axon compartments in the developed platform are designed to perform four sets of six different localized biomolecular treatments simultaneously on a single device. In addition, the novel microfluidic configuration allows culture medium of 24 axon compartments to be replenished altogether by a single aspiration process, making high-throughput drug screening a reality. Full article
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<p>Illustrations of the high-throughput compartmentalized neuron culture platform: (<b>A</b>) three layers (i.e., culture medium reservoir layer, compartment layer with two through-holes at each axon compartment, cell culture substrate layer with the ridge structure) composing the platform; (<b>B</b>) an illustration showing the axon isolation from the neuronal somata by the shallow height of the microchannels connecting the soma compartment and the axon compartment; and (<b>C</b>) schematic illustrations of the assembled device showing cross-sections. Inset: A close-up view of the axon compartments showing the fluidic flow during the one-step culture medium replenishment process. Blue dotted circle indicates a branch channel that connects the outflow hole with the medium outflow channel.</p>
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<p>Fabrication processes of the high-throughput compartmentalized neuron culture platform; (<b>A</b>) substrate layer, (<b>B</b>) compartment layer, (<b>C</b>) reservoir layer.</p>
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<p>SEM images of the fabricated devices: (<b>A</b>,<b>B</b>) PMMA master showing precisely patterned microchannel array by the hot-embossing process; (<b>C</b>–<b>E</b>) bottom-side of the final PDMS layer showing 3 μm deep and 20 μm wide microchannels connecting the soma compartment and the axon compartments; (<b>F</b>) axon compartment of the PDMS master, in which the round pillar-like structures allows pre-defined holes to be made on the final PDMS layer; and (<b>G</b>,<b>H</b>) pre-defined through-holes on the axon compartments of the final PDMS layer.</p>
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<p>Numerical simulation results of the culture medium flow profiles during the replenishment process. (<b>A</b>) 3D illustration of the culture medium outflow channel connected to the axon compartments and the reservoirs as well as the culture medium exchange port. (<b>B</b>) Normalized culture medium flow streamline showing the flow direction from the reservoirs to the culture medium exchange port. (<b>C</b>) <span class="html-italic">y</span>-<span class="html-italic">z</span> cross-sectional view at the center of branch channel part of which enlarged views show the design used for matching the fluidic resistance at each axon compartments. Table illustrates the dimensions of each branch channel used. (<b>D</b>) <span class="html-italic">x</span>-<span class="html-italic">y</span> cross-sectional view at the culture medium outflow channel. (<b>E</b>) <span class="html-italic">x</span>-<span class="html-italic">z</span> cross-sectional view across the center of 12th branch channel part. Both (D) and (E) clearly show the culture medium flow profile collected at the medium exchange port through axon compartments and the culture medium outflow channel under a negative pressure applied condition.</p>
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<p>(<b>A</b>,<b>B</b>) Axons being isolated from the neuronal somata by the shallow microchannels connecting the soma compartment and the axon compartment. Red dotted lines indicate compartment boundaries. (<b>C</b>) Isolated axonal layer inside the soma compartment at DIV 12. Cells were stained with Calcein-AM for visualization. Scale bars: 50 µm.</p>
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<p>Cross-sections of the high-throughput compartmentalized neuron culture platform showing the fluidic isolation scheme during: (<b>A</b>) the culture medium replenishment process; and (<b>B</b>) localized biomolecular treatment.</p>
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<p>(<b>A</b>) Image of the high-throughput compartmentalized neuron culture platform with reservoirs filled with inks for visualization. Isolated axon (<b>B</b>) without the CSPG treatment (control) and (<b>C</b>) with the CSPG treatment inside the axon compartments. Cells were stained with Calcein-AM for visualization. Scale bars: 50 µm.</p>
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2214 KiB  
Communication
Microfluidic Autologous Serum Eye-Drops Preparation as a Potential Dry Eye Treatment
by Takao Yasui, Jumpei Morikawa, Noritada Kaji, Manabu Tokeshi, Kazuo Tsubota and Yoshinobu Baba
Micromachines 2016, 7(7), 113; https://doi.org/10.3390/mi7070113 - 4 Jul 2016
Cited by 1 | Viewed by 5440
Abstract
Dry eye is a problem in tearing quality and/or quantity and it afflicts millions of persons worldwide. An autologous serum eye-drop is a good candidate for dry eye treatment; however, the eye-drop preparation procedures take a long time and are relatively troublesome. Here [...] Read more.
Dry eye is a problem in tearing quality and/or quantity and it afflicts millions of persons worldwide. An autologous serum eye-drop is a good candidate for dry eye treatment; however, the eye-drop preparation procedures take a long time and are relatively troublesome. Here we use spiral microchannels to demonstrate a strategy for the preparation of autologous serum eye-drops, which provide benefits for all dry eye patients; 100% and 90% removal efficiencies are achieved for 10 μm microbeads and whole human blood cells, respectively. Since our strategy allows researchers to integrate other functional microchannels into one device, such a microfluidic device will be able to offer a new one-step preparation system for autologous serum eye-drops. Full article
(This article belongs to the Special Issue Micro/Nano Devices for Chemical Analysis)
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<p>A spiral microfluidic device. (<b>a</b>) Photograph of a spiral microfluidic device; scale bar, 10 mm. Microchannels are highlighted by Trypan blue dye solution. Channel width and height are 707 and 70.7 μm, respectively. Distance between two adjacent microchannels is 303 μm; (<b>b</b>) A magnified micrograph of part of a spiral microchannel, enclosed by the red dotted box in <a href="#micromachines-07-00113-f001" class="html-fig">Figure 1</a>a; scale bar, 100 μm. Ten-fold diluted microbeads (10 μm diameter) in phosphate buffered saline were focused at an equilibrium position close to the inner wall of the microchannel.</p>
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<p>Collection efficiency of 10 μm particles. Cross-sectional area was 50,000 μm<sup>2</sup>. Ten-fold diluted microbeads (10 μm diameter) in phosphate buffered saline were used. Error bars are the standard deviation for a series of measurements (<span class="html-italic">N</span> = 3). (<b>a</b>) Collection efficiency vs. aspect ratio of spiral microchannels. The aspect ratio is the ratio of channel height to width. The number of microchannel spirals was 7.5, and flow rate was 1000 μL/min; (<b>b</b>) Photographs of fabricated spiral microchannels with 0.5 to 7.5 circles. One circle is one spiral. The microchannels are highlighted by Trypan blue dye solution; (<b>c</b>) Collection efficiency vs. number of microchannel spirals. The aspect ratio of the microchannels was 0.1, and flow rate was 1000 μL/min; (<b>d</b>) Collection efficiency vs. flow rate. The aspect ratio of the microchannels was 0.1, and the number of microchannel spirals was 7.5.</p>
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<p>Collection efficiency of whole human blood cells. Cross-sectional area was 50,000 μm<sup>2</sup>, the aspect ratio was 0.1, and the number of microchannel spirals was 7.5. (<b>a</b>) Collection efficiency vs. flow rate. Initial hematocrit of blood samples was 0.25%; (<b>b</b>) Collection efficiency vs. whole blood concentration. Flow rate was 5000 μm/min; (<b>c</b>) Photographs of collected samples from inner and outer outlets after centrifugation. Flow rate was 5000 μm/min, and initial hematocrit of blood samples was 0.25%. Hemolyzed blood was not observed.</p>
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1718 KiB  
Article
Light-Addressable Potentiometric Sensor as a Sensing Element in Plug-Based Microfluidic Devices
by Ko-Ichiro Miyamoto, Takuya Sato, Minami Abe, Torsten Wagner, Michael J. Schöning and Tatsuo Yoshinobu
Micromachines 2016, 7(7), 111; https://doi.org/10.3390/mi7070111 - 1 Jul 2016
Cited by 18 | Viewed by 5553
Abstract
A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, [...] Read more.
A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement. Full article
(This article belongs to the Special Issue Micro/Nano Devices for Chemical Analysis)
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<p>(<b>a</b>) Test structure of the microfluidic device combined with LAPS; (<b>b</b>) Channel design with a chamber for merging and differential measurement; (<b>c</b>) Channel design to generate plugs on chip; (<b>d</b>) Test structure with two sample chambers, one merging chamber, and one sensing area.</p>
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<p>Schematic view of the measurement system.</p>
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<p>Detection of the plug by the photocurrent signal.</p>
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<p>(<b>a</b>) I-V curves measured for plugs with different pH values; (<b>b</b>) Inflection points of I-V curves plotted as a function of pH.</p>
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<p>(<b>a</b>) I-V curves for the second plug measured in the upstream before merging; (<b>b</b>) I-V curves for the merged plug measured in the downstream.</p>
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<p>Effect of fluorine treatment of channel on the variation of plug volume.</p>
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<p>(<b>a</b>) Temporal change of photocurrent after merging a plug of urea solution and that of urease solution. The photocurrent response varied depending on concentrations of urea; (<b>b</b>) Initial slope of photocurrent change as a function of the urea concentration.</p>
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4027 KiB  
Article
Design and Experiment of a Solder Paste Jetting System Driven by a Piezoelectric Stack
by Shoudong Gu, Xiaoyang Jiao, Jianfang Liu, Zhigang Yang, Hai Jiang and Qingqing Lv
Micromachines 2016, 7(7), 112; https://doi.org/10.3390/mi7070112 - 30 Jun 2016
Cited by 18 | Viewed by 7840
Abstract
To compensate for the insufficiency and instability of solder paste dispensing and printing that are used in the SMT (Surface Mount Technology) production process, a noncontact solder paste jetting system driven by a piezoelectric stack based on the principle of the nozzle-needle-system is [...] Read more.
To compensate for the insufficiency and instability of solder paste dispensing and printing that are used in the SMT (Surface Mount Technology) production process, a noncontact solder paste jetting system driven by a piezoelectric stack based on the principle of the nozzle-needle-system is introduced in this paper, in which a miniscule gap exists between the nozzle and needle during the jetting process. Here, the critical jet ejection velocity is discussed through theoretical analysis. The relations between ejection velocity and needle structure, needle velocity, and nozzle diameter were obtained by FLUENT software. Then, the prototype of the solder paste jetting system was fabricated, and the performance was verified by experiments. The effects of the gap between nozzle and needle, the driving voltage, and the nozzle diameter on the jetting performance and droplet diameter were obtained. Solder paste droplets 0.85 mm in diameter were produced when the gap between the nozzle and needle was adjusted to 10 μm, the driving voltage to 80 V, the nozzle diameter to 0.1 mm, and the variation of the droplet diameter was within ±3%. Full article
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<p>Structure of the solder paste jetting system.</p>
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<p>Working principle. (<b>a</b>) Normal state; (<b>b</b>) Needle upward movement; (<b>c</b>) Needle downward movement.</p>
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<p>Relation between the supply pressure and piezoelectric power.</p>
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<p>Physical model of the nozzle and needle.</p>
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<p>Velocity inside the nozzle orifice changes with distance <span class="html-italic">y</span>.</p>
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<p>Velocity distribution with different needle velocity. (<b>a</b>) <span class="html-italic">t</span> = 0.1 ms; (<b>b</b>) <span class="html-italic">t</span> = 0.15 ms; (<b>c</b>) <span class="html-italic">t</span> = 0.2 ms; (<b>d</b>) <span class="html-italic">t</span> = 0.25 ms.</p>
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<p>Velocity distribution with different needle velocity. (<b>a</b>) <span class="html-italic">t</span> = 0.1 ms; (<b>b</b>) <span class="html-italic">t</span> = 0.15 ms; (<b>c</b>) <span class="html-italic">t</span> = 0.2 ms; (<b>d</b>) <span class="html-italic">t</span> = 0.25 ms.</p>
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<p>Velocity and volume changes with nozzle diameter.</p>
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<p>Experiment test system of the solder paste jetting system.</p>
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<p>Droplet diameter changes with the gap between nozzle and needle.</p>
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<p>Solder paste suspension at the nozzle.</p>
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<p>Relationship between driving voltage and droplet diameter.</p>
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<p>Relationship between nozzle diameter and droplet diameter.</p>
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<p>Solder paste droplet diameter distribution.</p>
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945 KiB  
Article
A Multithread Nested Neural Network Architecture to Model Surface Plasmon Polaritons Propagation
by Giacomo Capizzi, Grazia Lo Sciuto, Christian Napoli and Emiliano Tramontana
Micromachines 2016, 7(7), 110; https://doi.org/10.3390/mi7070110 - 30 Jun 2016
Cited by 41 | Viewed by 5017
Abstract
Surface Plasmon Polaritons are collective oscillations of electrons occurring at the interface between a metal and a dielectric. The propagation phenomena in plasmonic nanostructures is not fully understood and the interdependence between propagation and metal thickness requires further investigation. We propose an ad-hoc [...] Read more.
Surface Plasmon Polaritons are collective oscillations of electrons occurring at the interface between a metal and a dielectric. The propagation phenomena in plasmonic nanostructures is not fully understood and the interdependence between propagation and metal thickness requires further investigation. We propose an ad-hoc neural network topology assisting the study of the said propagation when several parameters, such as wavelengths, propagation length and metal thickness are considered. This approach is novel and can be considered a first attempt at fully automating such a numerical computation. For the proposed neural network topology, an advanced training procedure has been devised in order to shun the possibility of accumulating errors. The provided results can be useful, e.g., to improve the efficiency of photocells, for photon harvesting, and for improving the accuracy of models for solid state devices. Full article
(This article belongs to the Special Issue Micro/Nano Photonic Devices and Systems)
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<p>Implemented geometry in COMSOL (<b>left</b>), and geometry that models Surface Plasmon Polaritons (SPP) propagation from a metal-dielectric interface (<b>right</b>).</p>
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<p>The simulation survey coverage in the features space concerning the excitation wavelength <math display="inline"> <semantics> <msub> <mi>λ</mi> <mn>0</mn> </msub> </semantics> </math> and the adopted tickness <span class="html-italic">t</span>.</p>
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<p>The real part (<b>left</b>) and the imaginary part (<b>right</b>) of the dielectric constant of various noble metals, such as Au, Ag and Mb.</p>
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<p>The proposed Nested Neural Network Architecture (NNNA).</p>
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<p>Global performance plot of the implemented Nested Neural Network Architecture (NNNA) (<b>left panel</b>), and a comparison with the performances obtained by using two separate Feed Forward Neural Networks (FFNNs) (<b>right panel</b>).</p>
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<p>The obtained results: the model error <math display="inline"> <semantics> <msub> <mi>E</mi> <msub> <mi>λ</mi> <mrow> <mi>S</mi> <mi>P</mi> <mi>P</mi> </mrow> </msub> </msub> </semantics> </math> for the prediction of <math display="inline"> <semantics> <msub> <mi>λ</mi> <mrow> <mi>S</mi> <mi>P</mi> <mi>P</mi> </mrow> </msub> </semantics> </math> computed as in Equation (<a href="#FD11-micromachines-07-00110" class="html-disp-formula">11</a>). The (<b>left</b>) shows the prediction error for <math display="inline"> <semantics> <msub> <mi>λ</mi> <mrow> <mi>S</mi> <mi>P</mi> <mi>P</mi> </mrow> </msub> </semantics> </math> and the (<b>right</b>) shows its absolute value.</p>
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<p>The obtained results: the model error <math display="inline"> <semantics> <msub> <mi>E</mi> <msub> <mi>L</mi> <mrow> <mi>S</mi> <mi>P</mi> <mi>P</mi> </mrow> </msub> </msub> </semantics> </math> for the prediction of <math display="inline"> <semantics> <msub> <mi>L</mi> <mrow> <mi>S</mi> <mi>P</mi> <mi>P</mi> </mrow> </msub> </semantics> </math> computed as in Equation (<a href="#FD11-micromachines-07-00110" class="html-disp-formula">11</a>). The (<b>left</b>) shows the prediction error for <math display="inline"> <semantics> <msub> <mi>L</mi> <mrow> <mi>S</mi> <mi>P</mi> <mi>P</mi> </mrow> </msub> </semantics> </math> and the (<b>right</b>) shows its absolute value.</p>
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5208 KiB  
Article
3D Printed Paper-Based Microfluidic Analytical Devices
by Yong He, Qing Gao, Wen-Bin Wu, Jing Nie and Jian-Zhong Fu
Micromachines 2016, 7(7), 108; https://doi.org/10.3390/mi7070108 - 28 Jun 2016
Cited by 59 | Viewed by 12848
Abstract
As a pump-free and lightweight analytical tool, paper-based microfluidic analytical devices (μPADs) attract more and more interest. If the flow speed of μPAD can be programmed, the analytical sequences could be designed and they will be more popular. This reports presents a novel [...] Read more.
As a pump-free and lightweight analytical tool, paper-based microfluidic analytical devices (μPADs) attract more and more interest. If the flow speed of μPAD can be programmed, the analytical sequences could be designed and they will be more popular. This reports presents a novel μPAD, driven by the capillary force of cellulose powder, printed by a desktop three-dimensional (3D) printer, which has some promising features, such as easy fabrication and programmable flow speed. First, a suitable size-scale substrate with open microchannels on its surface is printed. Next, the surface of the substrate is covered with a thin layer of polydimethylsiloxane (PDMS) to seal the micro gap caused by 3D printing. Then, the microchannels are filled with a mixture of cellulose powder and deionized water in an appropriate proportion. After drying in an oven at 60 °C for 30 min, it is ready for use. As the different channel depths can be easily printed, which can be used to achieve the programmable capillary flow speed of cellulose powder in the microchannels. A series of microfluidic analytical experiments, including quantitative analysis of nitrite ion and fabrication of T-sensor were used to demonstrate its capability. As the desktop 3D printer (D3DP) is very cheap and accessible, this device can be rapidly printed at the test field with a low cost and has a promising potential in the point-of-care (POC) system or as a lightweight platform for analytical chemistry. Full article
(This article belongs to the Special Issue 3D Printing: Microfabrication and Emerging Concepts)
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<p>Fabrication process of microfluidic analytical device: (<b>a</b>) Substrate fabrication process; (<b>b</b>) Recyclable fabrication process of the hydrophilic cellulose powder channels.</p>
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<p>Comparison between the PDMS coated substrate and uncoated substrate: (<b>a</b>) PH test on the fabricated microfluidic device; (<b>b</b>) PDMS uncoated substrate washed by water after PH test (inset: water contact angle image of PDMS uncoated substrate); (<b>c</b>) PDMS coated substrate washed by water after PH test (inset: water contact angle image of PDMS coated substrate).</p>
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<p>Cellulose powder channels fabricated with different proportion: (<b>a</b>) Comparison between the fabricated channels; (<b>b</b>) Blue dye was dropped to test the channels’ quality.</p>
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<p>Scanning electron microscopy of cellulose powder in fabricated device and Whatman No. 1: (<b>a</b>) Microstructure of cellulose powder under microscope (50×); (<b>b</b>) Microstructure of cellulose powder under microscope (200×); (<b>c</b>) Microstructure of chromatography paper Whatman No. 1 under microscope (50×); (<b>d</b>) Microstructure of chromatography paper Whatman No. 1 under microscope (200×); (<b>e</b>) A dying test on a μ3DPAD with a channel of 4 mm width; (<b>f</b>) Gray value distribution of the dye in the channel.</p>
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<p>Resolution of μ3DPADs: (<b>a</b>) The resolution of the hydrophilic channels and the channel’s image under the microscope (100×); (<b>b</b>) The resolution of the hydrophobic barriers and the barrier's image under the microscope (100×).</p>
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<p>Relationship between channel depth and flow time: (<b>a</b>) The flow trend of red dye in 8 channels with a gradient depth; (<b>b</b>) Quantitative analysis on the relationship between channel depth and flow time; (<b>c</b>) The linear relationship of speed and the depth.</p>
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<p>Flow speed control in 3D channels. The left channel and the right channel all have four segments with the different depth and the same segment length.</p>
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<p>The encapsulation of the microfluidic analytical device: (<b>a</b>) Model graph of the device in closed state; (<b>b</b>) Model graph of the device in open state; (<b>c</b>) Dropping indicating solution in physical model in open state; (<b>d</b>) Dropping test solution in physical model in open state; (<b>e</b>) Physical model graph of the device in closed state.</p>
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<p>Time-lapse image of two different dyes diffusing in the fabricated Y device: (<b>a</b>) Microfluidic Y device with two different fluid path lengths; (<b>b</b>) Microfluidic Y device with the same path length.</p>
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<p>Colorimetric assay of nitrite via color-reaction by using microfluidic analytical device: (<b>a</b>) Image of the testing microfluidic analytical device; (<b>b</b>) Curve for nitrite ion.</p>
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1406 KiB  
Article
Quantification of Vortex Generation Due to Non-Equilibrium Electrokinetics at the Micro/Nanochannel Interface: Spectral Analysis
by Seung Jun Lee, Tae-Joon Jeon, Sun Min Kim and Daejoong Kim
Micromachines 2016, 7(7), 109; https://doi.org/10.3390/mi7070109 - 27 Jun 2016
Cited by 3 | Viewed by 4671
Abstract
We report on our investigation of a low Reynolds number non-equilibrium electrokinetic flow in a micro/nanochannel platform. Non-equilibrium electrokinetic phenomena include so-called concentration polarization in a moderate electric field and vortex formation in a high electric field. We conducted a spectral analysis of [...] Read more.
We report on our investigation of a low Reynolds number non-equilibrium electrokinetic flow in a micro/nanochannel platform. Non-equilibrium electrokinetic phenomena include so-called concentration polarization in a moderate electric field and vortex formation in a high electric field. We conducted a spectral analysis of non-equilibrium electrokinetic vortices at a micro/nanochannel interface. We found that periodic vortices are formed while the frequency varies with the applied voltages and solution concentrations. At a frequency as high as 60 Hz, vortex generation was obtained with the strongest electric field and the lowest concentration. The power spectra show increasing frequency with increasing voltage or decreasing concentration. We expect that our spectral analysis results will be useful for micromixer developers in the micromachine research field. Full article
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<p>Schematic of the micro/nano channel device and the probing point for spectral analysis. The microchannel is 15 µm deep, 150 µm wide, and 1.5 cm long. The nanochannel is 10 µm wide and 50 nm deep. Inset: microscopic image of the fabricated microchannel and nanochannel.</p>
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<p>Images of vortex generation near the micro/nanochannel interface.</p>
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<p>Example of the power spectrum.</p>
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<p>Spectral analysis results with different applied voltages.</p>
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<p>Spectral analysis results with different solution concentrations.</p>
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1769 KiB  
Review
Farewell to Animal Testing: Innovations on Human Intestinal Microphysiological Systems
by Tae Hyun Kang and Hyun Jung Kim
Micromachines 2016, 7(7), 107; https://doi.org/10.3390/mi7070107 - 27 Jun 2016
Cited by 29 | Viewed by 11723
Abstract
The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal [...] Read more.
The human intestine is a dynamic organ where the complex host-microbe interactions that orchestrate intestinal homeostasis occur. Major contributing factors associated with intestinal health and diseases include metabolically-active gut microbiota, intestinal epithelium, immune components, and rhythmical bowel movement known as peristalsis. Human intestinal disease models have been developed; however, a considerable number of existing models often fail to reproducibly predict human intestinal pathophysiology in response to biological and chemical perturbations or clinical interventions. Intestinal organoid models have provided promising cytodifferentiation and regeneration, but the lack of luminal flow and physical bowel movements seriously hamper mimicking complex host-microbe crosstalk. Here, we discuss recent advances of human intestinal microphysiological systems, such as the biomimetic human “Gut-on-a-Chip” that can employ key intestinal components, such as villus epithelium, gut microbiota, and immune components under peristalsis-like motions and flow, to reconstitute the transmural 3D lumen-capillary tissue interface. By encompassing cutting-edge tools in microfluidics, tissue engineering, and clinical microbiology, gut-on-a-chip has been leveraged not only to recapitulate organ-level intestinal functions, but also emulate the pathophysiology of intestinal disorders, such as chronic inflammation. Finally, we provide potential perspectives of the next generation microphysiological systems as a personalized platform to validate the efficacy, safety, metabolism, and therapeutic responses of new drug compounds in the preclinical stage. Full article
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<p>Schematics of static culture models using human intestinal epithelial cells: (<b>a</b>) an epithelial monolayer has been grown on a semipermeable insert in the Transwell; (<b>b</b>) a collagen membrane patterned with crypt-like topography is incorporated in replacement of the porous membrane in the Transwell [<a href="#B34-micromachines-07-00107" class="html-bibr">34</a>]. Caco-2 cells (orange) can overlay the topological collagen surface to form a monolayer; and (<b>c</b>) a pseudo-3D intestine model has the hydrogel-based villous microarchitecture. An inset image shows a top view of Caco-2 cells grown on villous scaffolds. Reproduced by permission of John Wiley and Sons. All rights reserved [<a href="#B35-micromachines-07-00107" class="html-bibr">35</a>].</p>
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<p>Schematic illustrations of microfluidic models mimicking human intestinal pathophysiology: (<b>a</b>) a microfluidic device consists of upper (AP side) and lower (BL side) layers integrated with stirrer-based micropumps and optical fibers. Caco-2 cells are cultured on a semipermeable membrane in the AP side culture chamber. Reproduced by permission of the Royal Society of Chemistry. All rights reserved [<a href="#B57-micromachines-07-00107" class="html-bibr">57</a>]; (<b>b</b>) a cross-section view of a microfluidic device to evaluate intestinal absorption under fluidic conditions. Reproduced by permission of The Japan Society for Analytical Chemistry. All rights reserved [<a href="#B58-micromachines-07-00107" class="html-bibr">58</a>]; and (<b>c</b>) a microfluidic model for the co-culture of epithelial and bacterial cells. The device provides pneumatically-actuated trapping regions for providing bacterial islands around epithelial cells. Each bacterial island (1200 mm in diameter with 1000 mm in distance) has a separate inlet and an outlet for providing nutrients and removing wastes from the island. Reproduced by permission of Royal Society of Chemistry. All rights reserved [<a href="#B62-micromachines-07-00107" class="html-bibr">62</a>].</p>
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<p>An organomimetic human gut-on-a-chip microphysiological system: (<b>a</b>) a photographic image of a gut-on-a-chip microdevice. Arrows indicate the direction of flow in the microchannels (blue, luminal flow; red, capillary flow); (<b>b</b>) a schematic of a gut-on-a-chip displaying the flexible nature to exert peristalsis-like, vacuum-driven mechanical deformations. VC, vacuum chamber; and (<b>c</b>) an overlaid confocal immunofluorescence image showing a horizontal cross-section view of intestinal villi co-cultured with GFP <span class="html-italic">E. coli</span> (green). Brush border membrane (F-actin, red) and nuclei (DAPI, blue) are fluorescently highlighted.</p>
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<p>A simplified schematic illustration comparing the human intestinal microenvironment in healthy versus diseased conditions caused by chronic inflammation. In the diseased condition, inflamed intestinal microenvironment results in the leaky gut epithelium in accordance with the infection of pathogenic bacteria, increased level of bacterial endotoxins such as lipopolysaccharides (LPS), and recruitment of circulating immune cells.</p>
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<p>A schematic diagram of the transcytosis of monoclonal antibody (mAb) drugs across the lumen-mesenchyme-capillary tissue interface. Intravenously-administered mAb drugs (blue) bind to the neonatal Fc receptor (FcRn), in which the internalized endosome functions as a vehicle to carry this complex from the capillary layer into the lamina propria (a right bottom inset with a dotted circle). Released mAb drugs capture disposed proinflammatory cytokines (secreted by activated immune cells during IBD. Orally-delivered mAb drugs (red) can also be tested in this microphysiological system in situ (a right top inset with a dotted circle).</p>
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5404 KiB  
Review
Cell Monitoring and Manipulation Systems (CMMSs) based on Glass Cell-Culture Chips (GC3s)
by Sebastian M. Buehler, Marco Stubbe, Sebastian M. Bonk, Matthias Nissen, Kanokkan Titipornpun, Ernst-Dieter Klinkenberg, Werner Baumann and Jan Gimsa
Micromachines 2016, 7(7), 106; https://doi.org/10.3390/mi7070106 - 24 Jun 2016
Cited by 13 | Viewed by 8639
Abstract
We developed different types of glass cell-culture chips (GC3s) for culturing cells for microscopic observation in open media-containing troughs or in microfluidic structures. Platinum sensor and manipulation structures were used to monitor physiological parameters and to allocate and permeabilize cells. Electro-thermal [...] Read more.
We developed different types of glass cell-culture chips (GC3s) for culturing cells for microscopic observation in open media-containing troughs or in microfluidic structures. Platinum sensor and manipulation structures were used to monitor physiological parameters and to allocate and permeabilize cells. Electro-thermal micro pumps distributed chemical compounds in the microfluidic systems. The integrated temperature sensors showed a linear, Pt1000-like behavior. Cell adhesion and proliferation were monitored using interdigitated electrode structures (IDESs). The cell-doubling times of primary murine embryonic neuronal cells (PNCs) were determined based on the IDES capacitance-peak shifts. The electrical activity of PNC networks was detected using multi-electrode arrays (MEAs). During seeding, the cells were dielectrophoretically allocated to individual MEAs to improve network structures. MEA pads with diameters of 15, 20, 25, and 35 µm were tested. After 3 weeks, the magnitudes of the determined action potentials were highest for pads of 25 µm in diameter and did not differ when the inter-pad distances were 100 or 170 µm. Using 25-µm diameter circular oxygen electrodes, the signal currents in the cell-culture media were found to range from approximately −0.08 nA (0% O2) to −2.35 nA (21% O2). It was observed that 60-nm thick silicon nitride-sensor layers were stable potentiometric pH sensors under cell-culture conditions for periods of days. Their sensitivity between pH 5 and 9 was as high as 45 mV per pH step. We concluded that sensorized GC3s are potential animal replacement systems for purposes such as toxicity pre-screening. For example, the effect of mefloquine, a medication used to treat malaria, on the electrical activity of neuronal cells was determined in this study using a GC3 system. Full article
(This article belongs to the Special Issue Advances in Microfluidic Devices for Cell Handling and Analysis)
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<p>Images of glass-based Pt sensors and actuators (for scaling and the arrangement on two different chip surfaces, see <a href="#micromachines-07-00106-f002" class="html-fig">Figure 2</a>). The structures were produced by sputtering glass wafers with 100-nm thick Pt layers. (<b>A</b>) temperature sensor; (<b>B</b>) IDES; (<b>C</b>) MEA; (<b>D</b>) two ground electrodes, which can also be used to stimulate cells; (<b>E</b>) scanning electron microscopy (SEM) image of a bare oxygen-sensor spot (diameter: 25 µm); (<b>F</b>) pH sensor with a rectangular pH-sensitive 1.24 mm × 0.46 mm area (insulated connector is black); (<b>G</b>) electroporation chip with a circular test volume and six electroporation electrodes of 80 µm in width and 4.65 mm in length, with electrode distances of 80, 100, 150, 300, and 450 µm, and temperature sensors at the top and the bottom; (<b>H</b>) ETµP with a 120-µm wide horizontal microfluidic channel. The black Pt structures form a heating meander with 30-µm wide intervals as well as two 100-µm wide field electrodes separated by 390 µm.</p>
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<p>(<b>A</b>) Microscopic image of the GNC surface (16 mm × 16 mm) with the integrated sensors: temperature probe (a); IDES (b); MEA (c); stimulating field and ground electrodes (d). An open circular glass trough was glued to the GNC surface (circles indicate the thickness of the trough wall). (<b>B</b>) Microscopic image of the glass-metabolic chip surface (22 mm × 27 mm) with five oxygen sensors (e); four pH sensors (f) and 6 IDESs (b). The microfluidic PDMS structure holding the microfluidic volume is light grey. The four circular structures are inlet or outlet connector sites.</p>
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<p>Temperature-dependent resistance values of five temperature sensors in five different GNCs at between 20 and 40 °C, as well as the averaged resistance values and standard deviations at 20 °C. More than 700 data points were obtained for each curve.</p>
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<p>(<b>A</b>) Microscopic image of a neuronal PNC network on the IDES of a GNC; (<b>B</b>) Frequency dependence of the IDES-capacitance differences (−∆<span class="html-italic">C</span>) (with-cells minus control (without cells)) [<a href="#B10-micromachines-07-00106" class="html-bibr">10</a>,<a href="#B51-micromachines-07-00106" class="html-bibr">51</a>]. The data obtained using eight GNCs were averaged over six DIV. The measurements revealed the characteristic magnitude and frequency shift of the −∆<span class="html-italic">C</span>-peak during cell proliferation; (<b>C</b>) Fit of Equation (3) to the absolute values of the −∆<span class="html-italic">C</span>-peak magnitudes shown in B.</p>
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<p>(<b>A</b>) Design of the MEA (electrode pad diameter: 35 µm); (<b>B</b>) PNCs allocated to the MEA-electrodes in the upper right quadrant through positive DEP (1 MHz, 16 V<sub>pp</sub>).</p>
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<p>(<b>A</b>) Neuronal network of PNCs isolated from the frontal cortex (E16, DIV28). Electrode pad diameter: 35 µm, rectangular pad-center distances: 170 µm; (<b>B</b>) Screenshot of the MEA server showing multiple repetitions of the action potential traces of two units detected via the same MEA pad. The peak-to-peak voltages of the large and small signals were approximately 238 and 76 µV, respectively; (<b>C</b>) Screenshot of the MEA server showing action potential-spike trains of 37 units that were detected via 34 electrode pads over 20 s.</p>
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<p>Averaged peak-to-peak voltages (see <a href="#micromachines-07-00106-f006" class="html-fig">Figure 6</a>B) of the action potentials of PNC networks that were detected depending on the MEA-pad diameter. The plotted data were obtained using 9 chips (15 µm), 12 chips (20 µm), 10 chips (25 µm) and 9 chips (35 µm). The average number of detected units per chip was 25.</p>
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<p>Decrease in the firing frequency of two units of a neuronal network upon exposure to mefloquine. The firing frequencies were averaged (horizontal lines) for 17 min before 10 µM mefloquine was added. The exponential decay functions could be fitted to the mefloquine-induced decrease in firing frequency. The averaged firing frequencies before the addition of mefloquine and the characteristic decay periods were 9.38 Hz and 13.64 min (solid line) and 7.81 Hz and 3.73 min (dashed line), respectively.</p>
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<p>Oxygen-sensor characterization and cell-culture measurements. (<b>A</b>) Results of cyclic voltammetry of air-saturated (21% O<sub>2</sub>) and oxygen-free (0% O<sub>2</sub>) media. The vertical dotted line at −650 mV indicates the potential used in the cell-culture measurements; (<b>B</b>) Time-dependent current at −650 mV. The current values in the cell cultures were recorded after 5 s after the voltage was applied (vertical dotted line; (<b>C</b>) Respiration measurements of MC3T3-E1 cells. The 5 min-long medium exchange performed every 5 h induced current peaks, which were neglected to determine the current-drop rates by linear fitting (tilted bars). Please note the slightly decreasing slopes of the consecutive bars.</p>
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<p>(<b>A</b>) Calibration measurements obtained using 60-nm thick Si<sub>3</sub>N<sub>4</sub> sensors. Linear fitting yielded a mean slope of −44.6 ± 2.1 mV per pH step (<span class="html-italic">R</span><sup>2</sup> = 0.99), which was independent of the direction of the pH change; (<b>B</b>) Acidification behavior of proliferating MC3T3-E1 and MG63 cells cultivated at 37 °C in the microfluidic volume of a glass metabolic chip (<a href="#micromachines-07-00106-f002" class="html-fig">Figure 2</a>B). The medium was exchanged over a five-min period every 5 h using a peristaltic medium-exchange pump. Increasingly rapid medium acidification rates were observed upon consecutive medium exchanges.</p>
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<p>Comparison of the pumping velocities measured using a passivated ETµP as shown in <a href="#micromachines-07-00106-f001" class="html-fig">Figure 1</a>A for media with conductivities of 0.01, 0.1 and 1.0 Sm<sup>−1</sup> (symbols: mean values ± SD of four measurements each) and the corresponding theoretical curves. The electrode voltage and the heating power were 20 V<sub>rms</sub> and 120 mW, respectively.</p>
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<p>Microscopic images of differently oriented chicken red blood cells suspended in propidium iodide-containing medium before (<b>A</b>) phase contrast and (<b>B</b>) fluorescence after electro-permeabilization. The cells were exposed to a 10-ms 10-kHz AC pulse of 16 V<sub>PP</sub>, corresponding to 200 kV·m<sup>−1</sup>, which passed between two parallel electrodes separated by 80 µm. Only cells with permeabilized membranes are penetrated by propidium iodide, which can be detected by fluorescence microscopy after it has bound to DNA or RNA.</p>
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