Micromachines, Volume 7, Issue 12 (December 2016) – 25 articles

One of the biggest challenges for tissue engineering is to efficiently provide oxygen and nutrients to cells on a three-dimensional (3D) engineered scaffold structure. Thus, achieving sufficient vascularization of the structure is a critical problem in tissue engineering. This facilitates the need to develop novel methods to enhance vascularization. Use of patterned hydrogel structures with multiscale channels can be used to achieve the required vascularization. Patterned structures need to be biocompatible and biodegradable. In this study, gelatin was used as the main part of a hydrogel to prepare a biological structure with 3D multiscale channels using bioprinting combined with selection of suitable materials and electrostatic spinning. Human umbilical vein endothelial cells (HUVECs) were then used to confirm efficacy of the structure, inferred from cell viability on different engineered construct designs. HUVECs were seeded on the surface of channels and cultured in vitro. HUVECs showed high viability and diffusion within the construct. This method can be used as a practical platform for the fabrication of engineered construct for vascularization. Full article

Squeeze-film damping and acceleration load are two major issues in the design of inertial micro-switches. In order to deeply and systematically study these two issues, this paper proposes a typical vertically-driven inertial micro-switch, wherein the air and electrode gaps were chosen to design the required damping ratio and threshold value, respectively. The switch was modeled by ANSYS Workbench, and the simulation program was optimized for computational accuracy and speed. Transient analysis was employed to investigate the relationship between the damping ratio, acceleration load, and the natural frequency, and the dynamic properties (including contact bounce, contact time, response time, and threshold acceleration) of the switch. The results can be used as a guide in the design of inertial micro-switches to meet various application requirements. For example, increasing the damping ratio can prolong the contact time of the switch activated by short acceleration duration or reduce the contact bounce of the switch activated by long acceleration duration; the threshold value is immune to variations in the damping effect and acceleration duration when the switch is quasi-statically operated; the anti-jamming capability of the switch can be improved by designing the sensing frequency of the switch to be higher than the acceleration duration but much lower than the other order frequencies of the switch. Full article

Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL of HC in a 60:40 (v/v) mixture of ethanol and water and the anti-solvent was milli-Q water. The microfluidic mixers were fabricated with an orifice diameter of the inner capillary ranging from 50 µm to 400 µm and operated at the aqueous to organic phase flow rate ratio ranging from 5 to 25. The size of the nanocrystals decreased with increasing aqueous to organic flow rate ratio. The counter-current flow microfluidic mixers provided smaller nanocrystals than the co-current flow devices under the same conditions and for the same geometry, due to smaller diameter of the organic phase stream in the mixing zone. The Z-average particle size of the drug nanocrystals increased from 210–280 nm to 320–400 nm after coating the nanocrystals with 0.2 wt % aqueous solution of hydroxypropyl methylcellulose (HPMC) in a stirred vial. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses carried out on the dried nanocrystals stabilized with HPMC, polyvinyl pyrrolidone (PVP), and sodium lauryl sulfate (SLS) were investigated and reported. The degree of crystallinity for the processed sample was lowest for the sample stabilised with HPMC and the highest for the raw HC powder. Full article

Fabrication of microchannels and associated electrodes to generate electrokinetic phenomena often involves costly materials and considerable effort. In this study, we used graphite pencil-leads as low cost, disposable 3D electrodes to investigate various electrokinetic phenomena in straight cylindrical microchannels, which were themselves fabricated by using a graphite rod as the microchannel mold. Individual pencil-leads were employed as the micro-electrodes arranged along the side walls of the microchannel. Efficient electrokinetic phenomena provided by the 3D electrodes, including alternating current electroosmosis (ACEO), induced-charge electroosmosis (ICEO), and dielectrophoresis (DEP), were demonstrated by the introduced pencil-lead based microfluidic devices. The electrokinetic phenomena were characterized by micro-particle image velocimetry (micro-PIV) measurements and microscopy imaging. Highly efficient electrokinetic phenomena using 3D pencil-lead electrodes showed the affordability and ease of this technique to fabricate microfluidic devices embedded with electrodes for electrokinetic fluid and particle manipulations. Full article

To increase the yield of the wafer-level Cu-Cu thermo-compression bonding method, certain surface pre-treatment methods for Cu are studied which can be exposed to the atmosphere before bonding. To inhibit re-oxidation under atmospheric conditions, the reduced pure Cu surface is treated by H₂/Ar plasma, NH₃ plasma and thiol solution, respectively, and is covered by Cu hydride, Cu nitride and a self-assembled monolayer (SAM) accordingly. A pair of the treated wafers is then bonded by the thermo-compression bonding method, and evaluated by the tensile test. Results show that the bond strengths of the wafers treated by NH₃ plasma and SAM are not sufficient due to the remaining surface protection layers such as Cu nitride and SAMs resulting from the pre-treatment. In contrast, the H₂/Ar plasma–treated wafer showed the same strength as the one with formic acid vapor treatment, even when exposed to the atmosphere for 30 min. In the thermal desorption spectroscopy (TDS) measurement of the H₂/Ar plasma–treated Cu sample, the total number of the detected H₂ was 3.1 times more than the citric acid–treated one. Results of the TDS measurement indicate that the modified Cu surface is terminated by chemisorbed hydrogen atoms, which leads to high bonding strength. Full article

Microfluidics and microfabrication have recently been established as promising tools for developing a new generation of in vitro cell culture microdevices. The reduced amounts of reagents employed within cell culture microdevices make them particularly appealing to drug screening processes. In addition, latest advancements in recreating physiologically relevant cell culture conditions within microfabricated devices encourage the idea of using such advanced biological models in improving the screening of drug candidates prior to in vivo testing. In this review, we discuss microfluidics-based models employed for chemical/drug screening and the strategies to mimic various physiological conditions: fine control of 3D extra-cellular matrix environment, physical and chemical cues provided to cells and organization of co-cultures. We also envision future directions for achieving multi-organ microfluidic devices. Full article

The prevention of glow-to-arc transition exhibited by micro dielectric barrier discharge (MDBD), as well as its long lifetime, has generated much excitement across a variety of applications. Silicon nitride (SiN_x) is often used as a dielectric barrier layer in DBD due to its excellent chemical inertness and high electrical permittivity. However, during fabrication of the MDBD devices with multilayer films for maskless nano etching, the residual stress-induced deformation may bring cracks or wrinkles of the devices after depositing SiN_x by plasma enhanced chemical vapor deposition (PECVD). Considering that the residual stress of SiN_x can be tailored from compressive stress to tensile stress under different PECVD deposition parameters, in order to minimize the stress-induced deformation and avoid cracks or wrinkles of the MDBD device, we experimentally measured stress in each thin film of a MDBD device, then used numerical simulation to analyze and obtain the minimum deformation of multilayer films when the intrinsic stress of SiN_x is −200 MPa compressive stress. The stress of SiN_x can be tailored to the desired value by tuning the deposition parameters of the SiN_x film, such as the silane (SiH₄)–ammonia (NH₃) flow ratio, radio frequency (RF) power, chamber pressure, and deposition temperature. Finally, we used the optimum PECVD process parameters to successfully fabricate a MDBD device with good quality. Full article

A high Q factor film bulk acoustic resonator operating in thickness shear mode excited by a lateral field is described in this paper. The influence of electrode parameters on the resonator performance is studied by the finite element method. The results showed that three key electrode parameters, including the gap, length and width, played important roles in the optimization of the resonator performance. The highest Q factor of up to 643 was obtained when the parallel electrodes were designed to be 100 µm × 10 µm with the electrode gap of 10 µm. Based on the simulation results, the AlN-based film bulk acoustic resonator with a solidly mounted structure was fabricated. The testing results showed that the real device operated at the resonance frequency of 1.94 GHz with the Q factor of 405 in air, 216 in water and 102 in phosphate buffered saline solution. Full article

This paper reports a versatile and irreversible bonding method for poly(dimethylsiloxane) (PDMS) and SU-8. The method is based on epoxide opening and dehydration reactions between surface-modified PDMS and SU-8. A PDMS replica is first activated via the low-cost lab equipment, i.e., the oxygen plasma cleaner or the corona treater. Then both SU-8 and plasma-treated PDMS samples are functionalized using hydrolyzed (3-aminopropyl)triethoxysilane (APTES). Ultimately, the samples are simply brought into contact and heated to enable covalent bonding. The molecular coupling and chemical reactions behind the bonding occurring at the surfaces were characterized by water contact angle measurement and X-ray photoelectron spectroscopy (XPS) analysis. The reliability of bonded PDMS-SU-8 samples was examined by using tensile strength and leakage tests, which revealed a bonding strength of over 1.4 MPa. The presented bonding method was also applied to create a metal-SU-8-PDMS hybrid device, which integrated SU-8 microfluidic structures and microelectrodes. This hybrid system was used for the effective trapping of microparticles on-chip, and the selective releasing and identification of predefined trapped microparticles. The hybrid fabrication approach presented here, based on the PDMS-SU-8 bonding, enables multifunctional integration in complex microfluidic devices. Full article

Bubble-propelled catalytic micromotors have recently been attracting much attention. A bubble-propulsion mechanism has the advantage of producing a stronger force and higher speed than other mechanisms for catalytic micromotors, but the nature of the fluctuated bubble generation process affects the motions of the micromotors, making it difficult to control their motions. Thus, understanding of the influence of fluctuating bubble propulsion on the motions of catalytic micromotors is important in exploiting the advantages of bubble-propelled micromotors. Here, we report experimental demonstrations of the bubble-propelled motions of propeller-shaped micromotors and numerical analyses of the influence of fluctuating bubble propulsion on the motions of propeller-shaped micromotors. We found that motions such as trochoid-like motion and circular motion emerged depending on the magnitude or symmetricity of fluctuations in the bubble-propulsion process. We hope that those results will help in the construction and application of sophisticated bubble-propelled micromotors in the future. Full article

A novel multi-source energy harvester based on solar and radioisotope energy sources is designed and simulated in this work. We established the calculation formulas for the short-circuit current and open-circuit voltage, and then studied and analyzed the optimization thickness of the semiconductor, doping concentration, and junction depth with simulation of the transport process of β particles in a semiconductor material using the Monte Carlo simulation program MCNP (version 5, Radiation Safety Information Computational Center, Oak Ridge, TN, USA). In order to improve the efficiency of converting solar light energy into electric power, we adopted PC1D (version 5.9, University of New South Wales, Sydney, Australia) to optimize the parameters, and selected the best parameters for converting both the radioisotope energy and solar energy into electricity. The results concluded that the best parameters for the multi-source energy harvester are as follows: Na is 1 × 10¹⁹ cm⁻³, Nd is 3.8 × 10¹⁶ cm⁻³, a PN junction depth of 0.5 μm (using the ¹⁴⁷Pm radioisotope source), and so on. Under these parameters, the proposed harvester can achieve a conversion efficiency of 5.05% for the ¹⁴⁷Pm radioisotope source (with the activity of 9.25 × 10⁸ Bq) and 20.8% for solar light radiation (AM1.5). Such a design and parameters are valuable for some unique micro-power fields, such as applications in space, isolated terrestrial applications, and smart dust in battlefields. Full article

In this paper, we report the numerical calculations for a thermo-optical model and the temperature sensitivity of a fiber Bragg grating (FBG) sensor. The thermally-induced behaviors of a FBG sensor in the gas nitriding process were analyzed for temperatures ranging from 100–650 °C. The FBG consisted of properly chosen photosensitive fiber materials with an optimized thermo-optic coefficient. The experimental and optimized thermo-optic coefficient results were consistent in terms of temperature sensitivity. In these experiments, the temperature sensitivity of the FBG was found to be 11.9 pm/°C. Full article

This paper presents a fabrication method of capacitive micromachined ultrasonic transducers (CMUTs) by wafer direct bonding, which utilizes both the wet chemical and O₂plasma activation processes to decrease the bonding temperature to 400 °C. Two key surface properties, the contact angle and surface roughness, are studied in relation to the activation processes, respectively. By optimizing the surface activation parameters, a surface roughness of 0.274 nm and a contact angle of 0° are achieved. The infrared images and static deflection of devices are assessed to prove the good bonding effect. CMUTs having silicon membranes with a radius of 60 μm and a thickness of 2 μm are fabricated. Device properties have been characterized by electrical and acoustic measurements to verify their functionality and thus to validate this low-temperature process. A resonant frequency of 2.06 MHz is obtained by the frequency response measurements. The electrical insertion loss and acoustic signal have been evaluated. This study demonstrates that the CMUT devices can be fabricated by low-temperature wafer direct bonding, which makes it possible to integrate them directly on top of integrated circuit (IC) substrates. Full article

Using polymer materials to fabricate microfluidic devices provides simple, cost effective, and disposal advantages for both lab-on-a-chip (LOC) devices and micro total analysis systems (μTAS). Polydimethylsiloxane (PDMS) elastomer and thermoplastics are the two major polymer materials used in microfluidics. The fabrication of PDMS and thermoplastic microfluidic device can be categorized as front-end polymer microchannel fabrication and post-end microfluidic bonding procedures, respectively. PDMS and thermoplastic materials each have unique advantages and their use is indispensable in polymer microfluidics. Therefore, the proper selection of polymer microfabrication is necessary for the successful application of microfluidics. In this paper, we give a short overview of polymer microfabrication methods for microfluidics and discuss current challenges and future opportunities for research in polymer microfluidics fabrication. We summarize standard approaches, as well as state-of-art polymer microfluidic fabrication methods. Currently, the polymer microfluidic device is at the stage of technology transition from research labs to commercial production. Thus, critical consideration is also required with respect to the commercialization aspects of fabricating polymer microfluidics. This article provides easy-to-understand illustrations and targets to assist the research community in selecting proper polymer microfabrication strategies in microfluidics. Full article

We used inclined lithography to fabricate a pneumatic microvalve for tall microchannels such as those used to convey large cells. The pneumatic microvalve consists of three layers. The upper layer is the actual liquid microchannel, which has a parallelogram-shaped cross section of width 500 μm, height 100 μm, and an acute angle of 53.6°. The lower layer is a pneumatic microchannel that functions as an actuator, and the middle layer is a thin polydimethylsiloxane membrane between the upper and lower layers. The operation of the pneumatic microchannel actuator causes the thin membrane to bend, resulting in the bending of the liquid microchannel and its closure. It was confirmed that the closure of the liquid microchannel completely stopped the flow of the HeLa cell suspension that was used to demonstrate the operation of the microvalve. The HeLa cells that passed through the microchannel were also observed to retain their proliferation and morphological properties. Full article

We report on the realization of free-standing GaMnAs epilayer sheets using nanomachining techniques. By optimizing the growth conditions of the sacrificial Al_0.75Ga_0.25As layer, free-standing metallic GaMnAs (with ~6% Mn) microsheets (with T_C ~85 K) with integrated electrical probes are realized for magnetotransport measurements in the van der Pauw geometry. GaMnAs epilayer needs to be physically isolated to avoid buckling effects stemming from the release of lattice mismatch strain during the removal of the AlGaAs sacrificial layer. From finite element analysis, symmetrically placed and serpentine-shaped electrical leads induce minimal thermal stress at low temperatures. From magnetotransport measurements, changes in magnetic anisotropy are readily observed. Full article

We introduce a non-lithographical and vacuum-free method to pattern silicon. The method combines inkjet printing and metal assisted chemical etching (MaCE); we call this method “INKMAC”. A commercial silver ink is printed on top of a silicon surface to create the catalytic patterns for MaCE. The MaCE process leaves behind a set of silicon nanowires in the shape of the inkjet printed micrometer scale pattern. We further show how a potassium hydroxide (KOH) wet etching process can be used to rapidly etch away the nanowires, producing fully opened cavities and channels in the shape of the original printed pattern. We show how the printed lines (width 50–100 µm) can be etched into functional silicon microfluidic channels with different depths (10–40 µm) with aspect ratios close to one. We also used individual droplets (minimum diameter 30 µm) to produce cavities with a depth of 60 µm and an aspect ratio of two. Further, we discuss using the structured silicon substrate as a template for polymer replication to produce superhydrophobic surfaces. Full article

In this paper, we focus on the mechanical characterization of co-cultured spheroids of human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSC) (HUVEC/MSC spheroids). HUVEC/MSC spheroids aggregate during culture, thereby decreasing in size. Since this size decrease can be caused by the contractility generated by the actomyosin of MSCs, which are intracellular frames, we can expect that there is a temporal transition for the mechanical characteristics, such as stiffness, during culture. To measure the mechanical characteristics, we use a microfluidic chip that is integrated with force sensor probes. We show the details of the measurement configuration and the results of mechanical characterization of the HUVEC/MSC spheroids. To evaluate the stiffness of the spheroids, we introduce the stiffness index, which essentially shows a spring constant per unit size of the spheroid at a certain time during measurement. From the measurement results, we confirmed that the stiffness index firstly increased during the days of culture, although after four days of culture, the stiffness index decreased. We confirmed that the proposed system can measure the stiffness of HUVEC/MSC spheroids. Full article

To improve the jetting performance of liquid metals, an electromagnetic micro-jetting (EMJ) valve that realizes drop-on-demand (DOD) jetting while not involving any valve core or moving parts was designed. The influence of the lead angle of the nozzle on the jetting of liquid metal gallium (Ga) was investigated. It was found that the Lorentz force component parallel to the nozzle that jets the electrified liquid Ga is always larger than its internal friction; thus, jet can be generated with any lead angle but with different kinetic energies. Experimental results show that the mass of the jetting liquid, the jetting distance, the initial velocity of the jet, and the resulting kinetic energy of the jet increase first and then decrease. When the lead angle is 90°, the mass of the jetting liquid and the kinetic energy are at their maximum. When the angle is 80°, the initial velocity achieves its maximum, with a calculated value of 0.042 m/s. Moreover, very close and comparatively high kinetic energies are obtained at 80° and 90°, indicating that angles in between this range can produce a preferable performance. This work provides an important theoretical basis for the design of the EMJ valve, and may promote the development and application of micro electromagnetic jetting technology. Full article

The flow of liquids in centrifugal microfluidics is unidirectional and dominated by centrifugal and Coriolis forces (i.e., effective only at T-junctions). Developing mechanisms and discovering efficient techniques to propel liquids in any direction other than the direction of the centrifugal force has been the subject of a large number of studies. The capillary force attained by specific surface treatments, pneumatic energy, active and passive flow reciprocation and Euler force have been previously introduced in order to manipulate the liquid flow and push it against the centrifugal force. Here, as a new method, the moment of inertia of the liquid inside a chamber in a centrifugal microfluidic platform is employed to manipulate the flow and propel the liquid passively towards the disc center. Furthermore, the effect of the moment of inertia on the liquid in a rectangular chamber is evaluated, both in theory and experiments, and the optimum geometry is defined. As an application of the introduced method, the moment of inertia of the liquid is used in order to mix two different dyed deionized (DI) waters; the mixing efficiency is evaluated and compared to similar mixing techniques. The results show the potential of the presented method for pumping liquids radially inward with relatively high flow rates (up to 23 mm³/s) and also efficient mixing in centrifugal microfluidic platforms. Full article

In order to improve the output capacity of a piezoelectric pump when transferring gas, this paper presents a compact resonant piezoelectric diaphragm pump (hereinafter referred to as the piezoelectric diaphragm pump), which is driven by a rectangular piezoelectric vibrator. The compact structure can effectively release the vibrating constraints of the vibrator, and enlarge its center output displacement, so as to increase the volume change rate of the pump chamber. Based on the structure and the working principle of this piezoelectric diaphragm pump, a dynamic model for the diaphragm system is established in this paper, and an analysis on factors affecting the resonant frequency of the system is then conducted. We tested on the prototype under the driving voltage of 260 Vpp. The results show that the diaphragm system reaches resonance under the driving frequency of 265 Hz, which is very close to the fundamental frequency of check valve. Compared with the rectangular piezoelectric vibrator’s amplitude, the diaphragm’s amplitude is double amplified. At this time, the piezoelectric diaphragm pump achieves the maximum gas flow rate as 186.8 mL/min and the maximum output pressure as 56.7 kPa. Full article

Homogeneous and rapid mixing in microfluidic devices is difficult to accomplish, owing to the low Reynolds number associated with most flows in microfluidic channels. Here, an efficient electroosmotic micromixer based on a carefully designed lateral structure is demonstrated. The electroosmotic flow in this mixer with an asymmetrical structure induces enhanced disturbance in the micro channel, helping the fluid streams’ folding and stretching, thereby enabling appreciable mixing. Quantitative analysis of the mixing efficiency with respect to the potential applied and the flow rate suggests that the electroosmotic microfluidic mixer developed in the present work can achieve efficient mixing with low applied potential. Full article

Neural stem cells are of special interest due to their potential in neurogenesis to treat spinal cord injuries and other nervous disorders. Flow cytometry, a common technique used for cell sorting, is limited due to the lack of antigens and labels that are specific enough to stem cells of interest. Dielectrophoresis (DEP) is a label-free separation technique that has been recently demonstrated for the enrichment of neural stem/progenitor cells. Here we use numerical simulation to investigate the use of streaming DEP for the continuous sorting of neural stem/progenitor cells. Streaming DEP refers to the focusing of cells into streams by equilibrating the dielectrophoresis and drag forces acting on them. The width of the stream should be maximized to increase throughput while the separation between streams must be widened to increase efficiency during retrieval. The aim is to understand how device geometry and experimental variables affect the throughput and efficiency of continuous sorting of SC27 stem cells, a neurogenic progenitor, from SC23 cells, an astrogenic progenitor. We define efficiency as the ratio between the number of SC27 cells over total number of cells retrieved in the streams, and throughput as the number of SC27 cells retrieved in the streams compared to their total number introduced to the device. The use of cylindrical electrodes as tall as the channel yields streams featuring >98% of SC27 cells and width up to 80 µm when using a flow rate of 10 µL/min and sample cell concentration up to 10⁵ cells/mL. Full article

This article presents an overview on typical properties, technologies, and applications of liquid metal based flexible printed electronics. The core manufacturing material—room-temperature liquid metal, currently mainly represented by gallium and its alloys with the properties of excellent resistivity, enormous bendability, low adhesion, and large surface tension, was focused on in particular. In addition, a series of recently developed printing technologies spanning from personal electronic circuit printing (direct painting or writing, mechanical system printing, mask layer based printing, high-resolution nanoimprinting, etc.) to 3D room temperature liquid metal printing is comprehensively reviewed. Applications of these planar or three-dimensional printing technologies and the related liquid metal alloy inks in making flexible electronics, such as electronical components, health care sensors, and other functional devices were discussed. The significantly different adhesions of liquid metal inks on various substrates under different oxidation degrees, weakness of circuits, difficulty of fabricating high-accuracy devices, and low rate of good product—all of which are challenges faced by current liquid metal flexible printed electronics—are discussed. Prospects for liquid metal flexible printed electronics to develop ending user electronics and more extensive applications in the future are given. Full article

The surface acoustic wave (SAW) is effective for the manipulation of fluids and particles at microscale. The current approach of integrating interdigitated transducers (IDTs) for SAW generation into microfluidic channels involves complex and laborious microfabrication steps. These steps often require full access to clean room facilities and hours to align the transducers to the precise location. This work presents an affordable and innovative method for fabricating SAW-based microfluidic devices without the need for clean room facilities and alignment. The IDTs and microfluidic channels are fabricated using the same process and thus are precisely self-aligned in accordance with the device design. With the use of the developed fabrication approach, a few types of different SAW-based microfluidic devices have been fabricated and demonstrated for particle separation and active droplet generation. Full article