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Micromachines, Volume 8, Issue 6 (June 2017)

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Cover Story One of the major tasks of microfluidic technology is the automated handling of a small amount of [...] Read more.
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Editorial

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Open AccessEditorial Editorial for Special Issue: Advances in Microfluidic Devices for Cell Handling and Analysis
Micromachines 2017, 8(6), 184; doi:10.3390/mi8060184
Received: 6 June 2017 / Revised: 6 June 2017 / Accepted: 7 June 2017 / Published: 9 June 2017
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Abstract Microfluidics is a technology that is expanding rapidly in many areas of research, especially in the biological areas of cell handling and analysis.[...] Full article
(This article belongs to the Special Issue Advances in Microfluidic Devices for Cell Handling and Analysis)

Research

Jump to: Editorial, Review, Other

Open AccessFeature PaperArticle Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
Micromachines 2017, 8(6), 167; doi:10.3390/mi8060167
Received: 18 April 2017 / Revised: 18 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
PDF Full-text (2145 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings
[...] Read more.
Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings and human body environments for the cancer cells responding upon treatments of the anti-cancer agents. This major limitation urges for applying more reliable platforms for evaluating drugs with a higher throughput and cell aggregates in a more natural configuration. Here, we adopt a microfluidic device integrated with a differential micromixer and multiple microwell-containing channels (50 microwells per channel) for parallel screening of suspending cell spheroids treated by drugs with different combinations. We optimize the culture conditions of the surfactant-coated microwells in order to facilitate the spheroid formation of the breast cancer cell line (MDA-MB-231). We propose a new drug cocktail combined with three known chemotherapeutic agents (paclitaxel, epirubicin, and aspirin) for the drug screening of the cancer cell-spheroids. Our results exhibit the differential responses between planar cell layers in traditional culture wells and cell-spheroids grown in our microfluidic device, in terms of the apoptotic rates under treatments of the drug cocktails with different concentrations. These results reveal a distinct drug resistance between planar cell layers and cell-spheroids. Together, this work offers important guidelines on applying the cell-spheroid microfluidic cultures for development of more efficacious anticancer drugs. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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Open AccessFeature PaperArticle Large-Scale Fabrication of Porous Gold Nanowires via Laser Interference Lithography and Dealloying of Gold–Silver Nano-Alloys
Micromachines 2017, 8(6), 168; doi:10.3390/mi8060168
Received: 1 April 2017 / Revised: 11 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
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Abstract
In this work, we report on an efficient approach to fabricating large-area and uniform planar arrays of highly ordered nanoporous gold nanowires. The approach consists in dealloying Au–Ag alloy nanowires in concentrated nitric acid. The Au–Ag alloy nanowires were obtained by thermal annealing
[...] Read more.
In this work, we report on an efficient approach to fabricating large-area and uniform planar arrays of highly ordered nanoporous gold nanowires. The approach consists in dealloying Au–Ag alloy nanowires in concentrated nitric acid. The Au–Ag alloy nanowires were obtained by thermal annealing at 800 °C for 2 h of Au/Ag stacked nanoribbons prepared by subsequent evaporation of silver and gold through a nanograted photoresist layer serving as a mask for a lift-off process. Laser interference lithography was employed for the nanopatterning of the photoresist layer to create the large-area nanostructured mask. The result shows that for a low Au-to-Ag ratio of 1, the nanowires tend to cracks during the dealloying due to the internal residual stress generated during the dealloying process, whereas the increase of the Au-to-Ag ratio to 3 can overcome the drawback and successfully leads to the obtainment of an array of highly ordered nanoporous gold nanowires. Nanoporous gold nanowires with such well-regulated organization on a wafer-scale planar substrate are of great significance in many applications including sensors and actuators. Full article
(This article belongs to the Special Issue Scalable Micro/Nano Patterning)
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Open AccessArticle Handling in the Production of Wire-Based Linked Micro Parts
Micromachines 2017, 8(6), 169; doi:10.3390/mi8060169
Received: 28 February 2017 / Revised: 16 May 2017 / Accepted: 18 May 2017 / Published: 25 May 2017
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Abstract
For simplified processing and the enhancement of output rate in multi-stage production, micro parts are handled as linked parts. This contribution discusses handling specific challenges in production based on an exemplary process chain. The examined linked parts consist of spherical elements linked by
[...] Read more.
For simplified processing and the enhancement of output rate in multi-stage production, micro parts are handled as linked parts. This contribution discusses handling specific challenges in production based on an exemplary process chain. The examined linked parts consist of spherical elements linked by wire material. Hence, the diameter varies between the wire and part. Nevertheless, the linked parts must be handled accurately. The feed system is an important component too, but special focus is given to the guides in this present study. They must adapt to the diameters of both the parts and the linking wires. Two alternative variants of adaptive guides are presented and investigated under the aspects of precise radial guiding, vibration isolation, damping behavior and friction force. Full article
(This article belongs to the Special Issue Micro/Nano Manufacturing)
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Open AccessArticle Slurry Injection Schemes on the Extent of Slurry Mixing and Availability during Chemical Mechanical Planarization
Micromachines 2017, 8(6), 170; doi:10.3390/mi8060170
Received: 30 April 2017 / Revised: 26 May 2017 / Accepted: 26 May 2017 / Published: 29 May 2017
Cited by 1 | PDF Full-text (1987 KB) | HTML Full-text | XML Full-text
Abstract
In this study, slurry availability and the extent of the slurry mixing (i.e., among fresh slurry, spent slurry, and residual rinse-water) were varied via three different injection schemes. An ultraviolet enhanced fluorescence technique was employed to qualitatively indicate slurry availability and its flow
[...] Read more.
In this study, slurry availability and the extent of the slurry mixing (i.e., among fresh slurry, spent slurry, and residual rinse-water) were varied via three different injection schemes. An ultraviolet enhanced fluorescence technique was employed to qualitatively indicate slurry availability and its flow on the pad during polishing. This study investigated standard pad center area slurry application and a slurry injection system (SIS) that covered only the outer half of the wafer track. Results indicated that the radial position of slurry injection and the alteration of fluid mechanics by the SIS played important roles in slurry mixing characteristics and availability atop the pad. Removal rates were found to decrease with slurry availability, while a higher degree of slurry mixing decreased the fraction of fresh slurry and consequently lowered the removal rate. By using a hybrid system (i.e., a combination of slurry injection via SIS and standard pad center slurry application), the polishing process benefited from higher slurry availability and higher fraction of fresh slurry than the conventional pad center slurry application and the shorter SIS, individually. This work underscores the importance of optimum slurry injection geometry and flow for obtaining a more cost-effective and environmentally benign chemical mechanical planarization process. Full article
(This article belongs to the Special Issue Micro/Nano Manufacturing)
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Open AccessArticle Dynamical Modeling and Analysis of Viscoelastic Properties of Single Cells
Micromachines 2017, 8(6), 171; doi:10.3390/mi8060171
Received: 14 April 2017 / Revised: 13 May 2017 / Accepted: 22 May 2017 / Published: 1 June 2017
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Abstract
A single cell can be regarded as a complex network that contains thousands of overlapping signaling pathways. The traditional methods for describing the dynamics of this network are extremely complicated. The mechanical properties of a cell reflect the cytoskeletal structure and composition and
[...] Read more.
A single cell can be regarded as a complex network that contains thousands of overlapping signaling pathways. The traditional methods for describing the dynamics of this network are extremely complicated. The mechanical properties of a cell reflect the cytoskeletal structure and composition and are closely related to the cellular biological functions and physiological activities. Therefore, modeling the mechanical properties of single cells provides the basis for analyzing and controlling the cellular state. In this study, we developed a dynamical model with cellular viscoelasticity properties as the system parameters to describe the stress-relaxation phenomenon of a single cell indented by an atomic force microscope (AFM). The system order and parameters were identified and analyzed. Our results demonstrated that the parameters identified using this model represent the cellular mechanical elasticity and viscosity and can be used to classify cell types. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle Automatic and Selective Single Cell Manipulation in a Pressure-Driven Microfluidic Lab-On-Chip Device
Micromachines 2017, 8(6), 172; doi:10.3390/mi8060172
Received: 7 April 2017 / Revised: 9 May 2017 / Accepted: 16 May 2017 / Published: 1 June 2017
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Abstract
A microfluidic lab-on-chip device was developed to automatically and selectively manipulate target cells at the single cell level. The device is composed of a microfluidic chip, mini solenoid valves with negative-pressurized soft tubes, and a LabView®-based data acquisition device. Once a
[...] Read more.
A microfluidic lab-on-chip device was developed to automatically and selectively manipulate target cells at the single cell level. The device is composed of a microfluidic chip, mini solenoid valves with negative-pressurized soft tubes, and a LabView®-based data acquisition device. Once a target cell passes the resistive pulse sensing gate of the microfluidic chip, the solenoid valves are automatically actuated and open the negative-pressurized tubes placed at the ends of the collecting channels. As a result, the cell is transported to that collecting well. Numerical simulation shows that a 0.14 mm3 volume change of the soft tube can result in a 1.58 mm/s moving velocity of the sample solution. Experiments with single polystyrene particles and cancer cells samples were carried out to demonstrate the effectiveness of this method. Selectively manipulating a certain size of particles from a mixture solution was also achieved. Due to the very high pressure-driven flow switching, as many as 300 target cells per minute can be isolated from the sample solution and thus is particularly suitable for manipulating very rare target cells. The device is simple, automatic, and label-free and particularly suitable for isolating single cells off the chip one by one for downstream analysis. Full article
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Open AccessArticle Separated Type Atmospheric Pressure Plasma Microjets Array for Maskless Microscale Etching
Micromachines 2017, 8(6), 173; doi:10.3390/mi8060173
Received: 26 March 2017 / Revised: 26 April 2017 / Accepted: 10 May 2017 / Published: 1 June 2017
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Abstract
Maskless etching approaches such as microdischarges and atmospheric pressure plasma jets (APPJs) have been studied recently. Nonetheless, a simple, long lifetime, and efficient maskless etching method is still a challenge. In this work, a separated type maskless etching system based on atmospheric pressure
[...] Read more.
Maskless etching approaches such as microdischarges and atmospheric pressure plasma jets (APPJs) have been studied recently. Nonetheless, a simple, long lifetime, and efficient maskless etching method is still a challenge. In this work, a separated type maskless etching system based on atmospheric pressure He/O2 plasma jet and microfabricated Micro Electro Mechanical Systems (MEMS) nozzle have been developed with advantages of simple-structure, flexibility, and parallel processing capacity. The plasma was generated in the glass tube, forming the micron level plasma jet between the nozzle and the surface of polymer. The plasma microjet was capable of removing photoresist without masks since it contains oxygen reactive species verified by spectra measurement. The experimental results illustrated that different features of microholes etched by plasma microjet could be achieved by controlling the distance between the nozzle and the substrate, additive oxygen ratio, and etch time, the result of which is consistent with the analysis result of plasma spectra. In addition, a parallel etching process was also realized by plasma microjets array. Full article
(This article belongs to the Special Issue Microplasma Devices)
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Open AccessArticle Rapid Prototyping of a Micromotor with an Optical Rotary Encoder
Micromachines 2017, 8(6), 174; doi:10.3390/mi8060174
Received: 28 April 2017 / Revised: 24 May 2017 / Accepted: 29 May 2017 / Published: 2 June 2017
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Abstract
This study proposed a rapid prototyping fabrication method for micromotors that allowed us to develop both 1 mm and 1.5 mm diameter permanent-magnet synchronous motors (PMSMs) with an optical rotary encoder. First, an integrated electroforming method was proposed for combining stator housing and
[...] Read more.
This study proposed a rapid prototyping fabrication method for micromotors that allowed us to develop both 1 mm and 1.5 mm diameter permanent-magnet synchronous motors (PMSMs) with an optical rotary encoder. First, an integrated electroforming method was proposed for combining stator housing and flexible print circuit (FPC) coils to ease the manufacturing and assembly of micromotor components. This is particularly useful in the production of prototypes or small volumes of units. Second, an optical encoder was used to detect the rotational angle by means of a reflective code disk, an optical fiber, and a photo-detector. The micromotor was built with a code disk and an optical fiber. The code disk was designed to match the optical fiber and was made by photolithography and sputtering. Both the 1 mm and 1.5 mm diameter motors successfully achieved a rotational speed over 20,000 RPM and due to a 50 µm diameter optical fiber core, the encoders showed a resolution of 12 and 18 pulses per revolution (PPR), respectively. Full article
(This article belongs to the Special Issue State-Of-The-Art Micromachining)
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Open AccessArticle Rapid Screening of Graphitic Carbon Nitrides for Photocatalytic Cofactor Regeneration Using a Drop Reactor
Micromachines 2017, 8(6), 175; doi:10.3390/mi8060175
Received: 1 April 2017 / Revised: 24 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
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Abstract
Artificial photosynthesis is the imitation of natural photosynthesis, which promises an efficient way to use solar energy to synthesize organic matters, in which the key step is the coenzyme regeneration (NADH/NADPH). To achieve an efficient regeneration rate, various photocatalysts have been developed, such
[...] Read more.
Artificial photosynthesis is the imitation of natural photosynthesis, which promises an efficient way to use solar energy to synthesize organic matters, in which the key step is the coenzyme regeneration (NADH/NADPH). To achieve an efficient regeneration rate, various photocatalysts have been developed, such as g-C3N4 and mesoporous carbon nitride (mpg-C3N4). Generally, efficiency determination of different photocatalysts requires laborious experiments, high consumption of reagents, and a considerable amount of time. Here, based on the one-step artificial photosystem I method, we processed the analytical experiment in a very simple PDMS well (20 μL, a drop) to achieve a rapid screening of photocatalysts. For comparison, we used two types of graphitic carbon nitrides, few-layer g-C3N4 and mpg-C3N4. Compared with the slurry systems, firstly, the regeneration rate of mpg-C3N4 drop-reactor system is 4.3 times and 7.1 times those of the few-layer g-C3N4-slurry system and mpg-C3N4-slurry system, respectively. Secondly, this one-drop method reduces the typical verification time from 90 min to 5 min and lowers the liquid volume from 20 mL to 20 μL. Thirdly, this operation is a pump-free and soft lithography technique-free process. The miniaturization of the photocatalytic reaction in the PDMS well improves the regeneration rates, saves samples, and achieves high-throughput screening of multiple photocatalysts. Full article
(This article belongs to the Special Issue Photonic MEMS and Optofluidic Devices)
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Open AccessArticle Hollow Hydrogel Microfiber Encapsulating Microorganisms for Mass-Cultivation in Open Systems
Micromachines 2017, 8(6), 176; doi:10.3390/mi8060176
Received: 25 April 2017 / Revised: 23 May 2017 / Accepted: 1 June 2017 / Published: 3 June 2017
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Abstract
Open cultivation systems to monoculture microorganisms are promising for the commercialization of low-value commodities because they reduce the cultivation cost. However, contamination from biological pollutants frequently impedes the process. Here we propose a cultivation method using hollow hydrogel microfibers encapsulating microorganisms. Due to
[...] Read more.
Open cultivation systems to monoculture microorganisms are promising for the commercialization of low-value commodities because they reduce the cultivation cost. However, contamination from biological pollutants frequently impedes the process. Here we propose a cultivation method using hollow hydrogel microfibers encapsulating microorganisms. Due to the pore size, hydrogels allow nutrients and waste to pass through while preventing invading microorganisms from entering the microfiber. Experimental cultivation shows the growth of target bacteria inside the alginate hydrogel microfiber during exposure to invading bacteria. The membrane thickness of the microfiber greatly affects the bacterial growth due to changes in membrane permeability. The enhancement of mechanical toughness is also demonstrated by employing a double-network hydrogel for long-term cultivation. The hollow hydrogel microfiber has the potential to become a mainstream solution for mass-cultivation of microorganisms in an open system. Full article
(This article belongs to the Special Issue Biomedical Microfluidic Devices)
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Open AccessArticle Motor Power Signal Analysis for End-Point Detection of Chemical Mechanical Planarization
Micromachines 2017, 8(6), 177; doi:10.3390/mi8060177
Received: 9 April 2017 / Revised: 11 May 2017 / Accepted: 21 May 2017 / Published: 5 June 2017
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Abstract
In the integrated circuit (IC) manufacturing, in-situ end-point detection (EPD) is an important issue in the chemical mechanical planarization (CMP) process. In the paper, we chose the motor power signal of the polishing platen as the monitoring object. We then used the moving
[...] Read more.
In the integrated circuit (IC) manufacturing, in-situ end-point detection (EPD) is an important issue in the chemical mechanical planarization (CMP) process. In the paper, we chose the motor power signal of the polishing platen as the monitoring object. We then used the moving average method, which was appropriate for in-situ calculation process and made it easy to code for software development, to smooth the signal curve, and then studied the signal variation during the actual CMP process. The results demonstrated that the motor power signal contained the end-point feature of the metal layer removal, and the processed signal curve facilitated the feature extraction and it was relatively steady before and after the layer transition stage. In addition, the motor power signal variation of the polishing head was explored and further analysis of time delay was performed. Full article
(This article belongs to the Special Issue Microtribology, Adhesion and Surface Engineering)
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Open AccessArticle Fabrication of Functional Plastic Parts Using Nanostructured Steel Mold Inserts
Micromachines 2017, 8(6), 179; doi:10.3390/mi8060179
Received: 6 April 2017 / Revised: 15 May 2017 / Accepted: 25 May 2017 / Published: 6 June 2017
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Abstract
We report on the fabrication of sub-micro and nanostructured steel mold inserts for the replication of nanostructured immunoassay biochips. Planar and microstructured stainless steel inserts were textured at the sub-micron and nanoscale by combining nanosphere lithography and electrochemical etching. This allowed the fabrication
[...] Read more.
We report on the fabrication of sub-micro and nanostructured steel mold inserts for the replication of nanostructured immunoassay biochips. Planar and microstructured stainless steel inserts were textured at the sub-micron and nanoscale by combining nanosphere lithography and electrochemical etching. This allowed the fabrication of structures with lateral dimensions of hundreds of nanometers and aspect ratios of up to 1:2. Nanostructured plastic parts were produced by means of hot embossing and injection molding. Surface nanostructuring was used to control wettability and increase the sensitivity of an immunoassay. Full article
(This article belongs to the Special Issue Micro/Nano Manufacturing)
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Open AccessFeature PaperArticle Development of Temperature Control Solutions for Non-Instrumented Nucleic Acid Amplification Tests (NINAAT)
Micromachines 2017, 8(6), 180; doi:10.3390/mi8060180
Received: 24 April 2017 / Revised: 23 May 2017 / Accepted: 1 June 2017 / Published: 7 June 2017
PDF Full-text (1545 KB) | HTML Full-text | XML Full-text
Abstract
Non-instrumented nucleic acid amplification tests (NINAAT) are a novel paradigm in portable molecular diagnostics. They offer the high detection accuracy characteristic of nucleic acid amplification tests (NAAT) in a self-contained device, without the need for any external instrumentation. These Point-of-Care tests typically employ
[...] Read more.
Non-instrumented nucleic acid amplification tests (NINAAT) are a novel paradigm in portable molecular diagnostics. They offer the high detection accuracy characteristic of nucleic acid amplification tests (NAAT) in a self-contained device, without the need for any external instrumentation. These Point-of-Care tests typically employ a Lab-on-a-Chip for liquid handling functionality, and perform isothermal nucleic acid amplification protocols that require low power but high accuracy temperature control in a single well-defined temperature range. We propose temperature control solutions based on commercially available heating elements capable of meeting these challenges, as well as demonstrate the process by which such elements can be fitted to a NINAAT system. Self-regulated and thermostat-controlled resistive heating elements were evaluated through experimental characterization as well as thermal analysis using the finite element method (FEM). We demonstrate that the proposed solutions can support various NAAT protocols, as well as demonstrate an optimal solution for the loop-mediated isothermal amplification (LAMP) protocol. Furthermore, we present an Arduino-compatible open-source thermostat developed for NINAAT applications. Full article
(This article belongs to the Special Issue Application of Microfluidic Methodology for the Analysis of DNA)
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Open AccessArticle Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate
Micromachines 2017, 8(6), 181; doi:10.3390/mi8060181
Received: 11 February 2017 / Revised: 31 May 2017 / Accepted: 2 June 2017 / Published: 8 June 2017
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Abstract
Reconstitution of tissue morphology with inherent left–right (LR) asymmetry is essential for tissue/organ functions. For skeletal muscle, the largest tissue in mammalian organisms, successful myogenesis requires the regulation of the LR asymmetry to form the appropriate muscle alignment. However, the key factor for
[...] Read more.
Reconstitution of tissue morphology with inherent left–right (LR) asymmetry is essential for tissue/organ functions. For skeletal muscle, the largest tissue in mammalian organisms, successful myogenesis requires the regulation of the LR asymmetry to form the appropriate muscle alignment. However, the key factor for reproducing the LR asymmetry of skeletal tissues in a controllable, engineering context remains largely unknown. Recent reports indicate that cell chirality may underlie the LR development in tissue morphogenesis. Here, we report that a rigid substrate is required for the chirality of skeletal muscle cells. By using alternating micropatterned cell-adherent and cell-repellent stripes on a rigid substrate, we found that C2C12 skeletal muscle myoblasts exhibited a unidirectional tilted orientation with respect to the stripe boundary. Importantly, such chiral orientation was reduced when soft substrates were used instead. In addition, we demonstrated the key role of actin stress fibers in the formation of the chiral orientation. This study reveals that a rigid substrate is required for the chiral pattern of myoblasts, paving the way for reconstructing damaged muscle tissue with inherent LR asymmetry in the future. Full article
(This article belongs to the Special Issue Optofluidics 2016)
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Open AccessArticle Reliable and Accurate Release of Micro-Sized Objects with a Gripper that Uses the Capillary-Force Method
Micromachines 2017, 8(6), 182; doi:10.3390/mi8060182
Received: 22 March 2017 / Revised: 30 May 2017 / Accepted: 3 June 2017 / Published: 8 June 2017
PDF Full-text (4813 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
There have been recent developments in grippers that are based on capillary force and condensed water droplets. These are used for manipulating micro-sized objects. Recently, one-finger grippers have been produced that are able to reliably grip using the capillary force. To release objects,
[...] Read more.
There have been recent developments in grippers that are based on capillary force and condensed water droplets. These are used for manipulating micro-sized objects. Recently, one-finger grippers have been produced that are able to reliably grip using the capillary force. To release objects, either the van der Waals, gravitational or inertial-forces method is used. This article presents methods for reliably gripping and releasing micro-objects using the capillary force. The moisture from the surrounding air is condensed into a thin layer of water on the contact surfaces of the objects. From the thin layer of water, a water meniscus between the micro-sized object, the gripper and the releasing surface is created. Consequently, the water meniscus between the object and the releasing surface produces a high enough capillary force to release the micro-sized object from the tip of the one-finger gripper. In this case, either polystyrene, glass beads with diameters between 5–60 µm, or irregularly shaped dust particles of similar sizes were used. 3D structures made up of micro-sized objects could be constructed using this method. This method is reliable for releasing during assembly and also for gripping, when the objects are removed from the top of the 3D structure—the so-called “disassembling gripping” process. The accuracy of the release was lower than 0.5 µm. Full article
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Open AccessArticle “Z”-Shaped Rotational Au/Pt Micro-Nanorobot
Micromachines 2017, 8(6), 183; doi:10.3390/mi8060183
Received: 15 March 2017 / Revised: 27 May 2017 / Accepted: 29 May 2017 / Published: 8 June 2017
PDF Full-text (4426 KB) | HTML Full-text | XML Full-text
Abstract
Drug delivery, minimally-invasive surgery, and a hospital-in-the-body are highly desirable for meeting the rapidly growing needs of nanorobot. This paper reports a Z-shaped gold/platinum (Au/Pt) hybrid nanorobot which realizes the self-rotational movement without an external force field. The Z-shaped Au/Pt hybrid nanorobot was
[...] Read more.
Drug delivery, minimally-invasive surgery, and a hospital-in-the-body are highly desirable for meeting the rapidly growing needs of nanorobot. This paper reports a Z-shaped gold/platinum (Au/Pt) hybrid nanorobot which realizes the self-rotational movement without an external force field. The Z-shaped Au/Pt hybrid nanorobot was fabricated by focused ion beam (FIB) and plasma sputtering. The purity of the nanorobot was tested by energy dispersive X-ray analysis (EDS). The weight percentage of Pt and Au at the tip were 94.28% and 5.72%, respectively. The weight percentage of Pt and Au at the bottom were 17.39% and 82.75%, respectively. The size of the nanorobot was 2.58 × 10−16 m2 and the mass of the nanorobot was 8.768 × 10−8 kg. The driving force of the nanorobot was 9.76 × 10−14 N at the 6.9% concentration of hydrogen peroxide solution. The rotation speed was 13 rpm, 14 rpm, and 19 rpm at 5.6%, 6.2%, and 7.8% concentrations, respectively. Full article
(This article belongs to the Special Issue Micro/Nano Robotics, Volume II)
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Open AccessArticle Lithium Niobate Micromachining for the Fabrication of Microfluidic Droplet Generators
Micromachines 2017, 8(6), 185; doi:10.3390/mi8060185
Received: 9 March 2017 / Revised: 22 May 2017 / Accepted: 31 May 2017 / Published: 9 June 2017
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Abstract
In this paper, we present the first microfluidic junctions for droplet generation directly engraved on lithium niobate crystals by micromachining techniques, preparatory to a fully integrated opto-microfluidics lab-on-chip system. In particular, laser ablation technique and the mechanical micromachining technique are exploited to realise
[...] Read more.
In this paper, we present the first microfluidic junctions for droplet generation directly engraved on lithium niobate crystals by micromachining techniques, preparatory to a fully integrated opto-microfluidics lab-on-chip system. In particular, laser ablation technique and the mechanical micromachining technique are exploited to realise microfluidic channels in T- and cross junction configurations. The quality of both lateral and bottom surfaces of the channels are therefore compared together with a detailed study of their roughness measured by means of atomic force microscopy in order to evaluate the final performance achievable in an optofluidic device. Finally, the microfluidics performances of these water-in-oil droplets generators are investigated depending on these micromachining techniques, with particular focus on a wide range of droplet generation rates. Full article
(This article belongs to the Special Issue Ultrafast Laser Fabrication for Lab-on-a-Chip)
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Open AccessArticle 3D Finite Element Simulation of Micro End-Milling by Considering the Effect of Tool Run-Out
Micromachines 2017, 8(6), 187; doi:10.3390/mi8060187
Received: 26 April 2017 / Revised: 6 June 2017 / Accepted: 12 June 2017 / Published: 16 June 2017
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Abstract
Understanding the micro milling phenomena involved in the process is critical and difficult through physical experiments. This study presents a 3D finite element modeling (3D FEM) approach for the micro end-milling process on Al6082-T6. The proposed model employs a Lagrangian explicit finite element
[...] Read more.
Understanding the micro milling phenomena involved in the process is critical and difficult through physical experiments. This study presents a 3D finite element modeling (3D FEM) approach for the micro end-milling process on Al6082-T6. The proposed model employs a Lagrangian explicit finite element formulation to perform coupled thermo-mechanical transient analyses. FE simulations were performed at different cutting conditions to obtain realistic numerical predictions of chip formation, temperature distribution, and cutting forces by considering the effect of tool run-out in the model. The radial run-out is a significant issue in micro milling processes and influences the cutting stability due to chip load and force variations. The Johnson–Cook (JC) material constitutive model was applied and its constants were determined by an inverse method based on the experimental cutting forces acquired during the micro end-milling tests. The FE model prediction capability was validated by comparing the numerical model results with experimental tests. The maximum tool temperature was predicted in a different angular position of the cutter which is difficult or impossible to obtain in experiments. The predicted results of the model, involving the run-out influence, showed a good correlation with experimental chip formation and the signal shape of cutting forces. Full article
(This article belongs to the Special Issue Micro/Nano Manufacturing)
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Open AccessArticle Modeling the Influence of Tool Deflection on Cutting Force and Surface Generation in Micro-Milling
Micromachines 2017, 8(6), 188; doi:10.3390/mi8060188
Received: 24 May 2017 / Revised: 12 June 2017 / Accepted: 13 June 2017 / Published: 17 June 2017
PDF Full-text (2344 KB) | HTML Full-text | XML Full-text
Abstract
In micro-milling, cutting forces generate non-negligible tool deflection, which has a significant influence on the machining process and on workpiece accuracy. This paper investigates the tool deflection during micro-milling and its effect on cutting force and surface generation. The distribution of cutting forces
[...] Read more.
In micro-milling, cutting forces generate non-negligible tool deflection, which has a significant influence on the machining process and on workpiece accuracy. This paper investigates the tool deflection during micro-milling and its effect on cutting force and surface generation. The distribution of cutting forces acting on the tool is calculated with a mathematical model that considers tool elasticity and runout, and the tool deflection caused by the cutting forces is then obtained. Furthermore, an improved cutting force model and side wall surface generation model are established, including the tool deflection effect. Both cutting force and surface simulation models were verified by the micro-end-milling experiment, and the results show a very good agreement between the simulation and experiments. Full article
(This article belongs to the Special Issue State-Of-The-Art Micromachining)
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Open AccessArticle Parametric Analysis and Experimental Verification of a Hybrid Vibration Energy Harvester Combining Piezoelectric and Electromagnetic Mechanisms
Micromachines 2017, 8(6), 189; doi:10.3390/mi8060189
Received: 11 May 2017 / Revised: 12 June 2017 / Accepted: 15 June 2017 / Published: 18 June 2017
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Abstract
Considering coil inductance and the spatial distribution of the magnetic field, this paper developed an approximate distributed-parameter model of a hybrid energy harvester (HEH). The analytical solutions were compared with numerical solutions. The effects of load resistances, electromechanical coupling factors, mechanical damping ratio,
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Considering coil inductance and the spatial distribution of the magnetic field, this paper developed an approximate distributed-parameter model of a hybrid energy harvester (HEH). The analytical solutions were compared with numerical solutions. The effects of load resistances, electromechanical coupling factors, mechanical damping ratio, coil parameters and size scale on performance were investigated. A meso-scale HEH prototype was fabricated, tested and compared with a stand-alone piezoelectric energy harvester (PEH) and a stand-alone electromagnetic energy harvester (EMEH). The peak output power is 2.93% and 142.18% higher than that of the stand-alone PEH and EMEH, respectively. Moreover, its bandwidth is 108%- and 122.7%-times that of the stand-alone PEH and EMEH, respectively. The experimental results agreed well with the theoretical values. It is indicated that the linearized electromagnetic coupling coefficient is more suitable for low-level excitation acceleration. Hybrid energy harvesting contributes to widening the frequency bandwidth and improving energy conversion efficiency. However, only when the piezoelectric coupling effect is weak or medium can the HEH generate more power than the single-mechanism energy harvester. Hybrid energy harvesting can improve output power even at the microelectromechanical systems (MEMS) scale. This study presents a more effective model for the performance evaluation and structure optimization of the HEH. Full article
(This article belongs to the Special Issue Piezoelectric MEMS)
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Open AccessArticle Electroosmotic Flow in a Rough Nanochannel with Surface Roughness Characterized by Fractal Cantor
Micromachines 2017, 8(6), 190; doi:10.3390/mi8060190
Received: 6 May 2017 / Revised: 7 June 2017 / Accepted: 15 June 2017 / Published: 19 June 2017
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Abstract
Molecular dynamics simulation is applied to study the electroosmotic flow in rough nanochannels, with particular attention given to the fluid–solid interactions. In the simulation, the surface roughness is characterized by a fractal Cantor. The roles of roughness height and fractal dimension on nanoscale
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Molecular dynamics simulation is applied to study the electroosmotic flow in rough nanochannels, with particular attention given to the fluid–solid interactions. In the simulation, the surface roughness is characterized by a fractal Cantor. The roles of roughness height and fractal dimension on nanoscale electroosmotic flow are examined and analyzed. The concentration distributions, zeta potential and electroosmotic velocity are presented and investigated. The results indicate that surface roughness plays a significant role in the fluid–solid interaction and nanoscale electroosmotic flow. The distribution of dipole angle for water molecules in both the near-wall region and middle region is almost unaffected by surface roughness; however, a significant difference of dipole angle distribution is observed in the fluid region away from the wall. Interestingly, the concentration distributions, electroosmotic velocity and zeta potential are highly affected by the surface fractal dimension, even with the same roughness height. Full article
(This article belongs to the Special Issue Micro/Nano-Chip Electrokinetics, Volume II)
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Open AccessArticle Improvement of GNSS Carrier Phase Accuracy Using MEMS Accelerometer-Aided Phase-Locked Loops for Earthquake Monitoring
Micromachines 2017, 8(6), 191; doi:10.3390/mi8060191
Received: 18 May 2017 / Revised: 6 June 2017 / Accepted: 16 June 2017 / Published: 19 June 2017
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Abstract
When strong earthquake occurs, global navigation satellite systems (GNSS) measurement errors increase significantly. Combined strategies of GNSS/accelerometer data can estimate better precision in displacement, but are of no help to carrier phase measurement. In this paper, strong-motion accelerometer-aided phase-locked loops (PLLs) are proposed
[...] Read more.
When strong earthquake occurs, global navigation satellite systems (GNSS) measurement errors increase significantly. Combined strategies of GNSS/accelerometer data can estimate better precision in displacement, but are of no help to carrier phase measurement. In this paper, strong-motion accelerometer-aided phase-locked loops (PLLs) are proposed to improve carrier phase accuracy during strong earthquakes. To design PLLs for earthquake monitoring, the amplitude-frequency characteristics of the strong earthquake signals are studied. Then, the measurement errors of PLLs before and after micro electro mechanical systems (MEMS) accelerometer aiding are analyzed based on error models. Furthermore, tests based on a hardware simulator and a shake table are carried out. Results show that, with MEMS accelerometer aiding, the carrier phase accuracy of the PLL decreases little under strong earthquakes, which is consistent with the models analysis. Full article
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Open AccessArticle Three-Dimensional Calcium Alginate Hydrogel Assembly via TiOPc-Based Light-Induced Controllable Electrodeposition
Micromachines 2017, 8(6), 192; doi:10.3390/mi8060192
Received: 31 March 2017 / Revised: 12 June 2017 / Accepted: 15 June 2017 / Published: 19 June 2017
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Abstract
Artificial reconstruction of three-dimensional (3D) hydrogel microstructures would greatly contribute to tissue assembly in vitro, and has been widely applied in tissue engineering and drug screening. Recent technological advances in the assembly of functional hydrogel microstructures such as microfluidic, 3D bioprinting, and micromold-based
[...] Read more.
Artificial reconstruction of three-dimensional (3D) hydrogel microstructures would greatly contribute to tissue assembly in vitro, and has been widely applied in tissue engineering and drug screening. Recent technological advances in the assembly of functional hydrogel microstructures such as microfluidic, 3D bioprinting, and micromold-based 3D hydrogel fabrication methods have enabled the formation of 3D tissue constructs. However, they still lack flexibility and high efficiency, which restrict their application in 3D tissue constructs. Alternatively, we report a feasible method for the fabrication and reconstruction of customized 3D hydrogel blocks. Arbitrary hydrogel microstructures were fabricated in situ via flexible and rapid light-addressable electrodeposition. To demonstrate the versatility of this method, the higher-order assembly of 3D hydrogel blocks was investigated using a constant direct current (DC) voltage (6 V) applied between two electrodes for 20–120 s. In addition to the plane-based two-dimensional (2D) assembly, hierarchical structures—including multi-layer 3D hydrogel structures and vessel-shaped structures—could be assembled using the proposed method. Overall, we developed a platform that enables researchers to construct complex 3D hydrogel microstructures efficiently and simply, which has the potential to facilitate research on drug screening and 3D tissue constructs. Full article
(This article belongs to the Special Issue Microdevices and Microsystems for Cell Manipulation)
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Open AccessArticle Ink-Jet Printing of Micro-Elelectro-Mechanical Systems (MEMS)
Micromachines 2017, 8(6), 194; doi:10.3390/mi8060194
Received: 21 March 2017 / Revised: 23 May 2017 / Accepted: 7 June 2017 / Published: 21 June 2017
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Abstract
Beyond printing text on paper, inkjet printing methods have recently been applied to print passive electrical and optical microparts, such as conductors, resistors, solder bumps and polymeric micro lenses. They are also useful to print micro-electro-mechanical systems (MEMS) as sub-millimeter sensor and actuator
[...] Read more.
Beyond printing text on paper, inkjet printing methods have recently been applied to print passive electrical and optical microparts, such as conductors, resistors, solder bumps and polymeric micro lenses. They are also useful to print micro-electro-mechanical systems (MEMS) as sub-millimeter sensor and actuator arrays, such as multifunctional skins applicable to robotic application and ambient monitoring. This paper presents the latest review of a few successful cases of printable MEMS devices. This review shows that inkjet printing is good for printing two-dimensional or surface MEMS devices from a small unit to an array over a large area. In the future, three-dimensional printing of multi-materials, from metal, plastic, to ceramic, will open the possibility of realizing more variety and function of a large-areal MEMS array, for a mobile electro-mechanical systems. Full article
(This article belongs to the Special Issue Bioprinting and 3D Printing in MEMS Technology)
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Open AccessArticle On the Application of Replica Molding Technology for the Indirect Measurement of Surface and Geometry of Micromilled Components
Micromachines 2017, 8(6), 195; doi:10.3390/mi8060195
Received: 24 May 2017 / Revised: 12 June 2017 / Accepted: 18 June 2017 / Published: 21 June 2017
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Abstract
The evaluation of micromilled parts quality requires detailed assessments of both geometry and surface topography. However, in many cases, the reduced accessibility caused by the complex geometry of the part makes it impossible to perform direct measurements. This problem can be solved by
[...] Read more.
The evaluation of micromilled parts quality requires detailed assessments of both geometry and surface topography. However, in many cases, the reduced accessibility caused by the complex geometry of the part makes it impossible to perform direct measurements. This problem can be solved by adopting the replica molding technology. The method consists of obtaining a replica of the feature that is inaccessible for standard measurement devices and performing its indirect measurement. This paper examines the performance of a commercial replication media applied to the indirect measurement of micromilled components. Two specifically designed micromilled benchmark samples were used to assess the accuracy in replicating both surface texture and geometry. A 3D confocal microscope and a focus variation instrument were employed and the associated uncertainties were evaluated. The replication method proved to be suitable for characterizing micromilled surface texture even though an average overestimation in the nano-metric level of the Sa parameter was observed. On the other hand, the replicated geometry generally underestimated that of the master, often leading to a different measurement output considering the micrometric uncertainty. Full article
(This article belongs to the Special Issue Micro/Nano Manufacturing)
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Open AccessArticle 3-Dimensional Plasmonic Substrates Based on Chicken Eggshell Bio-Templates for SERS-Based Bio-Sensing
Micromachines 2017, 8(6), 196; doi:10.3390/mi8060196
Received: 27 April 2017 / Revised: 14 June 2017 / Accepted: 15 June 2017 / Published: 21 June 2017
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Abstract
A simple technique is presented to fabricate stable and reproducible plasmonic substrates using chicken eggshell as bio-templates, an otherwise everyday waste material. The 3-dimensional (3D) submicron features on the outer shell (OS), inner shell (IS), and shell membrane (SM) regions are sputter coated
[...] Read more.
A simple technique is presented to fabricate stable and reproducible plasmonic substrates using chicken eggshell as bio-templates, an otherwise everyday waste material. The 3-dimensional (3D) submicron features on the outer shell (OS), inner shell (IS), and shell membrane (SM) regions are sputter coated with gold and characterized for surface-enhanced Raman scattering (SERS) performance with respect to coating thickness, enhancement factor (EF), hot-spots distribution, and reproducibility. The OS and IS substrates have similar EF (2.6 × 106 and 1.8 × 106, respectively), while the SM provides smaller EF (1.5 × 105) due to its larger characteristic feature size. The variability from them (calculated as relative standard deviation, %RSD) are less than 7, 15, and 9 for the OS, IS, and SM substrates, respectively. Due to the larger EF and better signal reproducibility, the OS region is used for label-free sensing and identification of Escherichia coli and Bacillus subtilis bacteria as an example of the potential SERS applications. It is demonstrated that the detection limit could reach the level of single bacterial cells. The OS and IS regions are also used as templates to fabricate 3D flexible SERS substrates using polydimethylsiloxane and characterized. The simple, low-cost, and green route of fabricating plasmonic substrates represents an innovative alternative approach without the needs for nanofabrication facilities. Coupled with hyperspectral Raman imaging, high-throughput bio-sensing can be carried out at the single pathogen level. Full article
(This article belongs to the Special Issue MEMS/NEMS for Biomedical Imaging and Sensing)
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Review

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Open AccessReview Microtechnologies for Cell Microenvironment Control and Monitoring
Micromachines 2017, 8(6), 166; doi:10.3390/mi8060166
Received: 18 November 2016 / Revised: 8 May 2017 / Accepted: 16 May 2017 / Published: 23 May 2017
Cited by 1 | PDF Full-text (3812 KB) | HTML Full-text | XML Full-text
Abstract
A great breadth of questions remains in cellular biology. Some questions cannot be answered using traditional analytical techniques and so demand the development of new tools for research. In the near future, the development of highly integrated microfluidic analytical platforms will enable the
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A great breadth of questions remains in cellular biology. Some questions cannot be answered using traditional analytical techniques and so demand the development of new tools for research. In the near future, the development of highly integrated microfluidic analytical platforms will enable the acquisition of unknown biological data. These microfluidic systems must allow cell culture under controlled microenvironment and high throughput analysis. For this purpose, the integration of a variable number of newly developed micro- and nano-technologies, which enable control of topography and surface chemistry, soluble factors, mechanical forces and cell–cell contacts, as well as technology for monitoring cell phenotype and genotype with high spatial and temporal resolution will be necessary. These multifunctional devices must be accompanied by appropriate data analysis and management of the expected large datasets generated. The knowledge gained with these platforms has the potential to improve predictive models of the behavior of cells, impacting directly in better therapies for disease treatment. In this review, we give an overview of the microtechnology toolbox available for the design of high throughput microfluidic platforms for cell analysis. We discuss current microtechnologies for cell microenvironment control, different methodologies to create large arrays of cellular systems and finally techniques for monitoring cells in microfluidic devices. Full article
(This article belongs to the Special Issue Advances in Microfluidic Devices for Cell Handling and Analysis)
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Open AccessReview Recent Advances and Future Perspectives on Microfluidic Liquid Handling
Micromachines 2017, 8(6), 186; doi:10.3390/mi8060186
Received: 23 May 2017 / Revised: 3 June 2017 / Accepted: 8 June 2017 / Published: 12 June 2017
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Abstract
The interdisciplinary research field of microfluidics has the potential to revolutionize current technologies that require the handling of a small amount of fluid, a fast response, low costs and automation. Microfluidic platforms that handle small amounts of liquid have been categorised as continuous-flow
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The interdisciplinary research field of microfluidics has the potential to revolutionize current technologies that require the handling of a small amount of fluid, a fast response, low costs and automation. Microfluidic platforms that handle small amounts of liquid have been categorised as continuous-flow microfluidics and digital microfluidics. The first part of this paper discusses the recent advances of the two main and opposing applications of liquid handling in continuous-flow microfluidics: mixing and separation. Mixing and separation are essential steps in most lab-on-a-chip platforms, as sample preparation and detection are required for a variety of biological and chemical assays. The second part discusses the various digital microfluidic strategies, based on droplets and liquid marbles, for the manipulation of discrete microdroplets. More advanced digital microfluidic devices combining electrowetting with other techniques are also introduced. The applications of the emerging field of liquid-marble-based digital microfluidics are also highlighted. Finally, future perspectives on microfluidic liquid handling are discussed. Full article
(This article belongs to the Special Issue Insights and Advancements in Microfluidics)
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Other

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Open AccessCorrection Correction: Liu, W. et al. A Highly Sensitive Humidity Sensor Based on Ultrahigh-Frequency Microelectromechanical Resonator Coated with Nano-Assembled Polyelectrolyte Thin Films. Micromachines, 2017, 8, 116
Micromachines 2017, 8(6), 178; doi:10.3390/mi8060178
Received: 26 May 2017 / Accepted: 30 May 2017 / Published: 5 June 2017
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Abstract In the published paper [1], there is an error in Figure 3.[...] Full article
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Open AccessOpinion Commercial Value and Challenges of Drop-Based Microfluidic Screening Platforms–An Opinion
Micromachines 2017, 8(6), 193; doi:10.3390/mi8060193
Received: 13 February 2017 / Revised: 8 May 2017 / Accepted: 1 June 2017 / Published: 20 June 2017
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Abstract
Developments in High Throughput Screening aim at maximizing the number of samples per time and reducing the cost per sample, e.g., by applying very small sample volumes. The ultimate technological step in miniaturization is moving from microtiter plate wells to droplets, and from
[...] Read more.
Developments in High Throughput Screening aim at maximizing the number of samples per time and reducing the cost per sample, e.g., by applying very small sample volumes. The ultimate technological step in miniaturization is moving from microtiter plate wells to droplets, and from batch-wise characterization to the continuous preparation and analysis of samples. A range of drop-based microfluidic screening platforms has emerged that benefit from drop-formation rates of thousands per second, perfect drop size uniformity, plug-flow and compartmentalization, and the possibility of continuously analyzing a train of drops. However, after many years of intensive research, only few commercial applications have been developed and substantial development in the field is still required to make them reliable and broadly applicable. Can academic research achieve this, given that most of the fundamental concepts have been described already, making it hard to publish a big story? Can start-up companies raise enough money to overcome the technical issues of drop-based screening platforms? This contribution addresses the question, focusing on how the different stakeholders in the field should interact so that disillusionment will not put a premature end to the development of drop-based screening technologies. Full article
(This article belongs to the Special Issue Droplet Microfluidics: Techniques and Technologies, Volume II)

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