• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2020-01-27
Oladayo Ogunyinka, Alexander Wright, Guido Bolognesi, Felipe Iza, Himiyage Chaminda Hemaka Bandulasena

Abstract Reactive species produced by atmospheric-pressure plasma (APP) are useful in many applications including disinfection, pretreatment, catalysis, detection and chemical synthesis. Most highly reactive species produced by plasma, such as ·OH, 1O2 and $${\text{O}}_{2}^{ \cdot - }$$, are short-lived; therefore, in situ generation is essential to transfer plasma products to the liquid phase efficiently. A novel microfluidic device that generates a dielectric barrier discharge (DBD) plasma at the gas–liquid interface and disperses the reactive species generated using microbubbles of ca. 200 µm in diameter has been developed and tested. As the bubble size affects the mass transfer performance of the device, the effect of operating parameters and plasma discharge on generated bubbles size has been studied. The mass transfer performance of the device was evaluated by transferring the reactive species generated to an aqueous solution containing dye and measuring percentage degradation of the dye. Monodisperse microbubbles (polydispersity index between 2 and 7%) were generated under all examined conditions, but for gas flow rate exceeding a critical value, a secondary break-up event occurred after bubble formation leading to multiple monodisperse bubble populations. The generated microbubble size increased by up to ~ 8% when the device was operated with the gas plasma in the dispersed phase compared to the case without the plasma due to thermal expansion of the feed gas. At the optimal operating conditions, initial dye concentration was reduced by ~ 60% in a single pass with a residence time of 5–10 s. This microfluidic chip has the potential to play a significant role in lab-on-a-chip devices where highly reactive species are essential for the process.

更新日期：2020-01-27
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2020-01-16
Barbara Francz, Rita Ungai-Salánki, Éva Sautner, Robert Horvath, Bálint Szabó

Although microliter-scale liquid handling with a handheld pipette is a routine task, pipetting nanoliter-scale volumes is challenging due to several technical difficulties including surface tension, adhesion and evaporation effects. We developed a fully automated piezoelectric micropipette with a precision of < 1 nanoliter, improving the efficiency of imaging-based single-cell isolation to above 90%. This improvement is crucial when sorting rare or precious cells, especially in medical applications. The compact piezoelectric micropipette can be integrated into various (bio)chemical workflows. It eliminates plastic tubes, valves, syringes, and pressure tanks. For high-quality phase-contrast illumination of the sample, e.g., cells or tiny droplets, we constructed rings of LEDs arranged concentrically to the micropipette. The same device can be readily used for single-cell printing and nanoliter-scale droplet printing of reagents using either fluorescent or transparent illumination on a microscope. We envision that this new technology will shortly become a standard tool for single-cell manipulations in medical diagnostics, e.g., circulating tumor cell isolation.

更新日期：2020-01-17
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2020-01-10
Xiaolong Liu, Zhiyuan Dong, Qiang Zhao, Gang Li

Abstract Micromilling is a flexible, inexpensive and rapid prototyping technique for polymer microfluidic devices. However, the applications of microfluidic devices fabricated by micromilling have been compromised by their poor surface quality. In this study, we demonstrated a gas-blowing-assisted (GBA) polydimethylsiloxane (PDMS) coating that is used to reduce the surface roughness of micromilled channels, yielding optical grade channel walls while simultaneously offering high flexibility in channel dimensions and morphology by controlling the coating parameters. In this method, a thin layer of PDMS is coated on the engraved substrate, and then a computer numerical control (CNC)-guided gas-blowing is used to selectively remove surplus PDMS prepolymer in channels, which results in a thin residual and smooth PDMS coating on the walls of channels. With this GBA PDMS coating, the channel surface roughness of below 8 nm could be achieved without the need of advanced polishing equipment or procedures. Furthermore, this method has the capability to fabricate non-rectangular microchannels with different shapes in cross-section depending on the process parameters, which benefits microvascular research and tissue engineering.

更新日期：2020-01-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-31
Anna Llorella, Marina Navarro-Segarra, Irene Merino-Jiménez, Juan Pablo Esquivel, Neus Sabaté

In this paper, we present a simple yet smart electro-fluidic platform that enables automatic time control in a very affordable and simple manner. The system is based on the electric detection of a fluid front when it crosses a particular area of a paper strip. The detection can be used to trigger the sequential activation or deactivation of different electronic modules (heating of molecular diagnostics, time interval detection, or readout of test results) with an accuracy within the range of minutes. The whole system is implemented with a few number of discrete electronic components such as transistors, resistors and capacitors that, if required, can be totally fabricated using printed electronics technology. This platform opens new possible applications for paper-based point-of care (POC) diagnostic devices and enables the possibility of these devices to introduce time control functions without the need for any external instrumentation and human action.

更新日期：2019-12-31
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-19
Shipra Verma, Siddhartha Panda

Abstract In heterogeneous microfluidic immunosensors, enhanced capture efficiencies of the antigens (Ag) in the carrier fluids by the surface-immobilized antibodies (Ab) facilitate lower detection limits and thus early detection of disease. Capture efficiency depends on the interplay of transport, reaction parameters and the geometry of the system. A detailed analysis on the enhanced capture efficiencies due to secondary flows in heterogeneous immunosensors has not received significant attention and is the theme of the present work. We conducted a systematic study to observe the significance of secondary forces on the capture efficiency, manifested as the average surface concentration (Cs,avg), in serpentine channels of different lengths (l) and radius of curvature (Rc) as a function of the Reynolds number (Re). Experimental observations were validated with numerical simulations. Micro-PIV studies at different planes and sections of the serpentine microchannels were conducted and matched with the simulated velocity profiles. Further investigation of the process and the geometrical parameters was conducted using numerical simulation and the behaviour of Cs,avg as a function of Re and Rc was plotted for different cases. A highlight of the present work are correlations of Cs,avg as a function of the Dean number (De), as well as its constituents (Re and α). The scientific studies of the geometrical and process parameters which affect the analyte capture advance the understanding of the phenomena and the proposed engineering correlations would be useful in the design of more efficient flow-based heterogeneous immunosensors.

更新日期：2019-12-19
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-16
Mehmet Akif Şahin, Barbaros Çetin, M. Bülent Özer

In the present study, a 3D device-level numerical model is implemented via finite element method to assess the effects of design and operating parameters on the separation performance of a microscale acoustofluidic device. Elastodynamic equations together with electromechanical coupling at the piezoelectric actuators for the stress field within the solid parts, Helmholtz equation for the acoustic field within fluid, and Navier–Stokes equations for the fluid flow are coupled for the simulations. Once the zero-acoustic and flow fields are obtained, the trajectories of the particles are obtained by employing point–particle approach. The particle trajectories are simulated for many particles with different sizes released from random initial locations. Separation performances of the different cases are evaluated based on described metrics such as purity, yield, percentage of particle stuck in the channel, the force acting on the particles, residence time and separation parameter.

更新日期：2019-12-17
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-12
Hanliang Zhu, Huanan Li, Haoqing Zhang, Zdenka Fohlerova, Sheng Ni, Jaroslav Klempa, Imrich Gablech, Jaromir Hubalek, Honglong Chang, Levent Yobas, Pavel Neuzil

The determination of the physical properties of fluids—such as the thermal characteristics, which include heat transfer time (Δt)—is becoming more challenging as system sizes shrink to micro- and nanometer scales. Hence, knowledge of these properties is crucial for the operation of devices requiring precise temperature (T) control, such as polymerase chain reactions, melting curve analysis (MCA), and differential scanning fluorimetry. In this paper, we introduced a flow-through microfluidic system to analyze thermal properties such as Δt among samples and the sidewall of a silicon chip using microscopic image analysis. We performed a spatial MCA with double-stranded deoxyribonucleic acid (dsDNA) and EvaGreen intercalator, using a flow-through microfluidic chip, and achieved a T gradient of ≈ 2.23 K mm−1. We calculated the mean value of Δt as ≈ 33.9 ms from a melting temperature (TM) location shift along the microchannel for a variable flow rate. Our system had a T resolution of ≈ 1.2 mK pixel−1 to distinguish different dsDNA molecules—based on the TM location within the chip—providing an option to use it as a high-throughput device for rapid DNA or protein analysis.

更新日期：2019-12-13
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-10
Jingji Liu, Xiaopeng Kong, Hongliang Wang, Yajun Zhang, Yiqiang Fan

This study proposed a novel method for the rapid fabrication of paper-based microfluidic devices using a roll-to-roll wax transfer method. In this approach, a custom-made device was designed and fabricated for the direct roll-to-roll wax transfer from commercially available wax ribbon to the surface of paper substrate. After wax transfer, a thermal reflow process was conducted to enable the melt wax penetration through the whole thickness of the hydrophilic paper substrate to form hydrophobic wax barriers. Compared with the conventional approaches for paper-based microfluidics (wax printing, photolithography, and inkjet printing), the proposed fabrication technique for paper-based microfluidic devices is suitable for the batch fabrication of paper-based microfluidic chips at high production speed. Additional advantages including simple fabrication process, low material and fabrication cost, low-energy consumption, and without the requirement of cleanroom environment or facilities. The paper-based microfluidics fabricated with the proposed roll-to-roll wax transfer method is widely adaptable for microfluidic applications in biological and chemical fields.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-07
Ryo Kurimoto, Hiroki Tsubouchi, Hisato Minagawa, Takahiro Yasuda

The pressure difference in gas–liquid Taylor flow in square microchannels with three different hydraulic diameters (190, 298, and 505 μm) were measured. Three liquids (Water and two types of glycerol-water solutions) were used as the liquid phase, and N2 gas was used as the gas phase. The experiments were carried out for the ranges of 1.98 × 10−3 < CaT < 0.132 and 2.61 < ReT < 661, where CaT and ReT are the capillary and Reynolds numbers based on the total volumetric flux, respectively. The measured pressure drop of Taylor bubbles based on the unit cell model was compared with existing models, and large discrepancies could be recognized. Dimensionless pressure drop of a Taylor bubble increased with the capillary number, and depends on the liquid viscosity and the hydraulic diameter at the same capillary number in the middle and high capillary number region, i.e., the inertia effect. Hence, a new pressure drop model including these effects as dimensionless numbers was developed based on the relationship between the pressure drop and liquid film thickness of a Taylor bubble, and it could show good agreement with the measured data. The pressure drop of Taylor flow could also be evaluated using the unit cell model with the developed model. In addition, a pressure drop model for Taylor flow based on only the total volumetric flux was developed in terms of convenience of prediction.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-12-06
Martin Oellers, Frieder Lucklum, Michael J. Vellekoop

A fluidic micromixer realized by two-photon polymerization writing is embedded in a predefined microchannel. The micromixer consists of a 3D defined channel system which swaps incoming fluid streams, resulting in laminar alternating streams consisting of the two liquids to be mixed. Due to the shortened diffusion length, mixing times are reduced dramatically to 50 ms or lower. The structure is designed in such a way that the fluidic resistance in each swapper channel is balanced, yielding equal distribution of the alternating streams. The mixer element has a total size of about $$225\times 100\times 50\,\upmu \hbox {m}^{3}$$, fitting exactly in a prefabricated microchannel. The structure is strongly anchored in the channel so that it can handle high flow rates of up to 100 $$\upmu \text {L/min}$$ (corresponding to an average flow velocity of $$400\,\text {mm/s}$$). A benefit of the fabrication method is the short processing time. The writing of one mixer element takes less than $$30\,\text {s}$$, so that a whole wafer can be processed in typically less than one hour.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-23
Nike Heinß, Sabine Alebrand, Jörn Wittek, Michael Baßler

Inertial migration of particles to a characteristic lateral equilibrium position in laminar micro-flows has been investigated under various aspects during the last decades. The majority of the studies deal with the equilibrium position of rigid particles and viscous droplets. Here, we compare the equilibrium velocity of viscoelastic cells and rigid polystyrene spheres in flow by applying the method of spatially modulated emission. The technique allows the precise determination of the equilibrium velocity of an object in flow, which has been found to depend on object characteristics like size in earlier studies. Here, we first show that the deformable cells move at higher equilibrium velocity than rigid polystyrene particles, thus revealing that a particle’s equilibrium velocity is related to its deformability—in addition to size. In a second set of experiments, we treat cells with the cytostatic agent colchicine, which results in a systematic decrease of the equilibrium velocity that is attributed to cell stiffening. This study thus provides evidence that the parameter cell deformability can be extracted from the equilibrium velocity based on spatially modulated emission, which opens up an alternative way for high-throughput cell-deformability characterization.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-22
Farzin Jahangiri, Tuuli Hakala, Ville Jokinen

We present a simple and facile method for long-term preservation of hydrophilicity of oxygen plasma-hydrophilized poly (dimethylsiloxane) (PDMS) by cold storage. We show that storage under temperature of − 80 °C can maintain superhydrophilicity of plasma-exposed PDMS for at least 100 days. Storage at − 15 °C and at 22 °C room temperature (RT) is shown to exhibit, respectively, about half and full recovery of the original hydrophobicity after 100 days in storage. Furthermore, we investigated the implications of the cold storage for microfluidic applications, the capillary filling rate and the ability of the flow to bypass geometrical obstacles in a microfluidic channel. It is shown that the preservation of capillary filling properties of microchannels is in close agreement with the contact angle (CA) measurements and that the colder the storage temperature, the better the capillary filling capability of the channels is preserved. We ascribe the significantly reduced recovery rate to reduced thermally activated relaxation phenomena such as diminished diffusion of low molecular weight species (LMW) in the polymer matrix at colder temperatures. This is supported by ATR-FTIR measurements of the OH vibration band over time for samples stored at different temperatures.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-21
Kailiang Zhang, Yukun Ren, Likai Hou, Ye Tao, Weiyu Liu, Tianyi Jiang, Hongyuan Jiang

We present a flexible and noninvasive approach for efficient continuous micromixing and microreaction based on direct current-induced thermal buoyancy convection in a single microfluidic unit. Theoretically, microfluids in this microsystem are unevenly heated by powering the asymmetrically arranged microheater. The thermal buoyancy convection is then formed to induce microvortices that cause effective fluidic interface disturbance, thereby promoting the diffusion and convective mass transfer. The temperature distribution and the convection flow in the microchip are first characterized and studied, which can be flexibly adjusted by changing the DC voltage. Then the mixing performance of the presented method is validated by joint numerical and experimental analyses. Specifically, at U = 7 V, the mixing efficiencies are higher than 90% as the flow rate is lower than Qv= 600 nL/s. So high-quality chemical or biochemical reactions needing both suitable heating and efficient mixing can be achieved using this method. Finally, as one example, we use this method to synthesize nano-sized cuprous oxide (Cu2O) particles by effectively mixing the Benedict’s solution and glucose buffer. Remarkably, the particle size can be tuned by changing the voltage and the concentration of Benedict’s solution. Therefore, this micromixer can be attractive for diverse applications needing homogeneous sample mixtures.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-20

Microfluidic-based sorting systems are an integral part of many biological applications, where sorting of cells, microorganisms, and particles is of interest. In this paper, a computational fluid dynamics model is established to expand investigations on a hybrid microparticle sorting method, which combines inertia-magnetic focusing and hydrodynamic separation, known as multiplex inertia-magnetic fractionation (MIMF). This microfluidic device consists of two regions, i.e. a narrow microchannel with a magnet on its side for inertial and magnetophoretic focusing of particles and a downstream wide hydrodynamic expansion zone for particles’ separation and imaging. A Lagrangian–Eulerian framework was adopted to simulate particle trajectories using the ANSYS-Fluent discrete phase modeling (DPM) approach. Acting forces that were considered to predict particle trajectories included the drag, inertial lift, Saffman lift, gravitational, and magnetophoretic forces. User-defined functions were used for inertial lift and magnetophoretic forces that are not built-in relations in the ANSYS-Fluent DPM. Numerical results were verified and validated against the experimental data for MIMF of 5 and 11 µm magnetic particles at flow rates of 0.5–5 mL/h. Particles fractionation throughput and purity in the expansion region could be predicted with errors of 6% and 2%, respectfully. The validated model was then used to perform a numerical parametric study on the unknown effects of magnetization, particle size, higher flow rates, and fluid viscosity on MIMF. The presented numerical approach can be used as a tool for future experimental design of inertia-magnetophoretic microfluidic particle sorting devices.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-20
Wang Liwei, Wu Xiao, Yu Weijie, Hao Pengfei, He Feng, Zhang Xiwen

When a high-speed droplet impacts on mesh screens, part of the droplet penetrates the screen through its pores and generates smaller secondary drops, which spray downstream in a conical distribution. This instantaneous phase fragmentation phenomenon has been widely utilized in liquid spray applications and multiple-phase liquid separation. During droplet deformation, the intense liquid–gas fragmentation can lead to high nonequilibrium effect, which makes it hard to simulate by traditional fluid computational method. In this study, for the first time, we provided a numerical method to simulate the entire process of penetration dynamic behaviors. This 3D droplet-impact model based on MDPD (many-body dissipative particle dynamics) method exhibits high stability. A special solid–liquid boundary condition was proposed and successfully reduced the massive computational resources wasted on the solid mesh surface. To verify our model, the impacting of a droplet on a flat surface and on a mesh screen were simulated, respectively. The result showed a good match with our previous drop impact study and our experiment of the whole process about a droplet fragmented into hundreds of small drops. We further studied the mass transfer ratio (the ratio of penetrated drops to the initial droplet) and the ejection angle (the angle of the spray cone). The mass transfer ratio and ejection angle can be approximated as a function of Weber number, solid fraction and mesh number by summarizing the regular drop-penetrated behaviors over initial speed and mesh number.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-18
V. Lochab, A. Yee, M. Yoda, A. T. Conlisk, S. Prakash

Dynamics of charged sub-micron or colloidal particles in a microfluidic device through cross-stream migration under combined pressure gradients and electric potential gradients was demonstrated using confocal microscopy. The microfluidic device was a rectangular cross-section poly(dimethylsiloxane) or PDMS microchannel sealed with a borosilicate glass lid to form a hybrid PDMS-glass device. We postulate that the reported particle migration may arise in response to electrophoretic particle slip, i.e., the difference between the particle and fluid velocities, due to the applied electric potential gradient across the microchannel. Colloidal particle migration was observed either towards or away from the microchannel walls depending on the relative directions for the applied potential and pressure gradients. When pressure gradient driving the fluid flow and potential gradient were applied in the same direction, colloidal particles migrate away from the microchannel walls. In the case of opposite directions for the pressure and potential gradients, colloidal particles migrate towards the microchannel walls and subsequently assemble into distinct bands next to both the bottom glass and top PDMS walls. The results reported here demonstrate that the particle dynamics due to electrophoresis in Poiseuille flow within a microchannel result in non-uniform spatial distributions of colloidal particles via cross-stream migration, with the ability to assemble particles into distinct band structures at channel walls. Such manipulation, once fully realized, could lead to several microfluidics applications in material synthesis, particle separation, and biosensing.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-14

Electrokinetic (EK) properties, such as the electro-osmotic flow (EOF), are influenced by surfactant adsorption at the solid–liquid interface. With the growing popularity of poly(methyl methacrylate) (PMMA) as the substrate for polymeric-based microfluidics, it is important to understand the effect of surfactants on EOF in these devices. Here, we investigate the effect of surfactant chain length and concentration on the electro-osmotic (EO) mobility induced by three cationic surfactants cetyl trimethylammonium bromide (CTAB), trimethylammonium bromide (TTAB), dodecyl trimethylammonium bromide (DTAB) in PMMA microcapillaries. The EO mobility curve as a function of concentration shows three regimes. First, at very low concentrations below 0.002 mM, the mobility is constant and approximately equal to the value obtained with the surfactant-free electrolyte (1 mM KCl). Next, the EOF reverses and mobility increases linearly with surfactant concentration. Finally, the mobility reaches a plateau at a concentration well below surfactant CMC (0.2-mM CTAB, 0.5-mM TTAB and 2-mM DTAB) and decreases at the vicinity of CMC. Our results show that the rate of change in mobility with respect to concentration is a linear function of chain length and increases with longer-chain surfactants. In addition, we deduce the magnitude of Van der Waals or cohesive energy between the adsorbed alkyl chains from the EO mobility values. For the alkyl trimethylammonium surfactants adsorbed on the hydrophobic surface of PMMA, this energy was found to be 0.114 kT smaller than the reported value for ionic surfactants adsorbed on a hydrophilic surface.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-14
Zhihua Pu, Jiaming Ma, Wenwen Li, Xiaochen Lai, Xiao Su, Haixia Yu, Dachao Li

This paper reports a flexible precise volume sensor with metal-on-polyimide (PI) electrodes to substitute for the peripheral ration pump of a microfluidic system, thus beneficial for integration and miniaturization. This in-channel volume sensor consists of multi-electrode pairs, and it can perform volume measurement of the fluid flowing through microchannels by testing the resistance variation of the electrode pairs, which makes the device possible to help automatically control the sample volume in the mixing and reacting processes inside a microfluidic chip without peripheral ration pumps. The electrode pairs of the sensor are fabricated on flexible PI surface directly by inkjet printing. Then, the electrodes with the PI substrate are transferred and sandwiched by a polydimethylsiloxane (PDMS) substrate layer and a PDMS channel layer to form the flexible precise volume sensor. This method overcomes the challenge of patterning metals on PDMS and the sandwiched PDMS–PI–PDMS structure is beneficial for integration with other PDMS-based microfluidic chips. The effects of electrode-tip shapes and numbers of the electrode pairs are also investigated. A novel calculating method is proposed to obtain more precise results when different numbers of electrode pairs are used in different situations. According to the experimental results, the more electrode pairs are used in the same spacing, the better measurement precision can be obtained. The volume sensor with optimized electrode-tip and multi-electrode pairs can detect the fluid volume in nanolitre scales with the relative error of < 0.8%. This work exhibits the potential to form a total lab-on-a-chip without peripheral ration pumps.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-13
Konstantinos Zografos, Simon J. Haward, Mónica S. N. Oliveira

In this study, we optimise two types of multi-stream configurations (a T-junction and a flow-focusing design) to generate a homogeneous extensional flow within a well-defined region. The former is used to generate a stagnation point flow allowing molecules to accumulate significant strain, which has been found very useful for performing elongational studies. The latter relies on the presence of opposing lateral streams to shape a main stream and generate a strong region of extension in which the shearing effects of fluid–wall interactions are reduced near the region of interest. The optimisations are performed in two (2D) and three dimensions (3D) under creeping flow conditions for Newtonian fluid flow. It is demonstrated that in contrast with the classical-shaped geometries, the optimised designs are able to generate a well-defined region of homogeneous extension. The operational limits of the obtained 3D optimised configurations are investigated in terms of Weissenberg number for both constant viscosity and shear-thinning viscoelastic fluids. Additionally, for the 3D optimised flow-focusing device, the operational limits are investigated in terms of increasing Reynolds number and for a range of velocity ratios between the opposing lateral streams and the main stream. For all obtained 3D optimised multi-stream configurations, we perform the experimental validation considering a Newtonian fluid flow. Our results show good agreement with the numerical study, reproducing the desired kinematics for which the designs are optimised.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-13
Zebing Mao, Kazuhiro Yoshida, Joon-wan Kim

The traditional power sources for generating droplets are bulky devices such as syringe pumps, constant pressure systems and so on, resulting in difficult integration with other microfluidic components. To overcome this limitation, we propose and develop a droplet generator with its power sources on a chip (22 × 21 × ~ 1 mm). The compact droplet generator consists of two ECF (electro-conjugate fluid) micropumps, a T-junction channel geometry made of SU-8, a water chamber and three I/O ports. In our methodology, the two ECF micropumps are used to pump the continuous phase fluid (oil) directly and the dispersed phase fluid (water) indirectly on a chip. ECF is a kind of functional and dielectric oil, which can generate a strong and active ECF jet when its corresponding electrodes are applied to high DC voltages. Our ECF micropump is composed of triangular prism and silt electrode pairs (TPSEs) and is able to control flow rates precisely on a chip. In our device, the water in oil droplet is formed by the T-junction geometry. Using MEMS technology, we successfully fabricate the droplet-generator-on-a-chip. Span 80 and dibutyl decanedioate (DBD, Tokyo Chemical Industry Co., Ltd) are used as the surfactant and one type of ECF, respectively. Prior to the characteristic experiments of the T-junction generator, we investigate viscosity, electrical conductivity and relative permittivity of the mixtures of DBD and Span 80 at different concentrations (0 wt%, 1 wt%, 3 wt% and 5 wt%). We also research the impact of the mixtures on the performance of ECF micropumps and the wettability of SU-8 fluidic channels. After that, we confirm the flow pattern diagrams of two-phase fluids, the generated droplet diameter and the droplet production rate for our droplet-generator. Therefore, our droplet generator powered by ECF micropumps can realize the droplet generation on a chip.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-08
Leslie Labarre, Daniele Vigolo

Foam stability often refers to the foam left to evolve with time in static conditions. However, in everyday life, foams are submitted to numerous deformations. A feature of foam stability is represented by the foam’s ability to resist to the deformation and to recover its initial properties after deformation. The technique developed here allows for a qualitative evaluation of the property of foam recovery after a deformation in a flow-focusing microfluidic device. The foam hysteretic behaviour was evaluated by introducing the analogous of a standard three-step test in which the recovery of viscosity is commonly studied over three deformation stages. The foam behaviour is analysed over an induced cycle of ascendant and descendant deformation at the wall, well controlled by varying the gas pressure for a constant liquid pressure. Thus, the recovery of the two-row foam pattern used as reference is studied after a high deformation phase corresponding to the bamboo pattern and the level of hysteresis is measured qualitatively. The samples investigated comprise a range of Newtonian aqueous solutions containing 5 cmc (critical micellar concentration) of sodium dodecyl sulphate (SDS). A retardation effect was observed leading to hysteresis caused by the increase in viscosity. A higher surface elasticity produced a smaller but non-negligible hysteresis due to an excess in elastic energy caused by the increase of the duration of the bubble rearrangements. The present study has gone some way towards enhancing our understanding of the mechanisms triggering or enhancing foam hysteresis in a microchannel. The findings will be of interest to many industrial processes where foams are submitted to a series of deformation steps along the process line from food industrial applications to biological systems.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-11-08
S. Melzig, F. Purr, T. Lorenz, Z. Yan, J. H. Finke, C. Schilde, A. Kwade, A. Dietzel

The production of functional particle systems is becoming increasingly important in many industries. In the early development of such products, there is often not a sufficient amount of educts available or the educts are expensive and/or toxic. For this purpose, lab-scale processes are used which often differ from the later production processes. Unfortunately, the processes have a direct impact on the product properties. That makes a subsequent transfer from the unconventional lab methods to the actual fabrication process necessary, which is often associated with problems. To avoid complex additional efforts in the development of new functional particle systems and, thus, shorten the time to market, a modular microfluidic spray dryer was developed. With our new microfluidic spray dryer made from glass, it is possible to produce droplet sizes and, thus, particle sizes similar to those of conventional spray dryers in the lab or even in the production but using only smallest quantities of starting materials (product volume flow rates down to 0.03 ml/min). During the development of the micro spray dryer, process and formulation parameters as well as various microchannel geometries were investigated to determine their influence on droplet formation and, thus, on product formation. The developed micro spray dryer can be operated with various formulations and material compositions, as the micro system is made of chemically inert material, is easy to clean, pressure-resistant and can be used in a wide range of pH values.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-10-29
Xin Min, Woo Soo Kim

Digital microfluidics (DMFs) show great potential in the fields of lab-on-a-chip applications for electro-chemical as well as biochemical sensing for decades. Various types of DMF devices have been demonstrated to improve their capabilities such as smaller device size for portability, higher reliability, and multi-purpose applications, etc. Among them, the electrowetting on dielectric (EWOD) is one of the most widely used mechanisms to manipulate droplets due to its good flexibility. On the other hand, the high-voltage application that required for EWOD-type DMF also limits the portability and dimension of the whole system. In this review, we discuss the DMFs which are powered by alternative sources other than electrical sources and evaluate their potential for future portable biochemical assays. Then, the demonstrations reported with the possibility beyond high voltage are discussed starting from lowering voltage requirement for EWODs to the unique methods using mechanical, optical, and energy harvesting to power DMF devices. Finally, the practical applications and prospective on the integrated multi-functional lab-on-a-chip applications are tackled.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-10-17
Tetsuro Tsuji, Yuki Matsumoto, Satoyuki Kawano

In this paper, we demonstrate nanoparticle flow control using an optical force in a confined nanospace. Using nanofabrication technologies, all-quartz-glass nanoslit channels with a sudden contraction are developed. Because the nanoslit height is comparable to the nanoparticle diameter, the motion of particles is restricted in the channel height direction, resulting in almost two-dimensional particle motion. The laser irradiates at the entrance of the sudden contraction channel, leading the trapped nanoparticles to form a cluster. As a result, the translocation of nanoparticles into the contraction channel is suppressed. Because the particle translocation restarts when the laser irradiation is stopped, we can control the nanoparticle flow into the contraction channel by switching the trapping and release of particles, realizing an intermittent flow of nanoparticles. Such a particle flow control technique in a confined nanospace is expected to improve the functions of nanofluidic devices by transporting a target material selectively to a desired location in the device.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-10-17
Di Li, Xingchen Shao, Joshua B. Bostwick, Xiangchun Xuan

Label-free separation of particles by an intrinsic property can be implemented in microfluidic devices through either an externally imposed field or an inherent flow-induced force. Among the latter type of passive techniques, elastic or elasto-inertial lift-based particle separation in non-Newtonian fluids has received a rapidly growing interest in the past decade. However, current demonstrations of particle separation in non-Newtonian fluids have all taken place in viscoelastic polymer or biological solutions. We demonstrate for the first time a continuous sheath-free separation of polystyrene particles in the flow of weakly elastic xanthan gum (XG) solution through a simple straight rectangular microchannel. This separation is fundamentally different from that in the flow of viscoelastic solutions. We explain the observed particle migrations in XG solutions using the competition of a strong wall-directed (because of the strong shear thinning effect) and a small center-directed (because of the weak elasticity effect) lateral force induced by normal stresses in a Poiseuille flow.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-10-16
Matheus J. T. Vargas, Michel Nieuwoudt, Rui Ming Yong, Frederique Vanholsbeeck, David E. Williams, M. Cather Simpson

Rapid, simple microchannel prototyping is critical for the development of modern microfluidic devices and platforms. Laser cutting (ablation) using a commercially available continuous wave (CW) CO2 laser followed by thermal bonding is one of the most common approaches for prototyping in thermoplastics such as polymethyl methacrylate (PMMA). However, this technique suffers from poorly controlled channel quality, inconsistent results from solvent-based post-processing, and inconsistency of thermal bonding. We have overcome these challenges through a systematic study of channel ablation in PMMA using a CW CO2 laser. A new solvent treatment approach results in clearly improved microchannel quality and processing consistency, with negligible residual solvent. Thermal bonding of the processed material showed fourfold increase in bonding strength with full retention of PMMA’s favourable optical clarity. As proof of concept, a high-quality three-layered microfluidic prototype is fabricated with this new method and its performance demonstrated.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2019-10-15
Erik S. Hamilton, Vahid Ganjalizadeh, Joel G. Wright, William G. Pitt, Holger Schmidt, Aaron R. Hawkins

3D hydrodynamic focusing was implemented with channel cross-section dimensions smaller than 10 μm. Microchannels were formed using sacrificial etching of two photoresist layers on a silicon wafer. The photoresist forms a plus-shaped prismatic focusing fluid junction which was coated with plasma-enhanced chemical-vapor-deposited oxide. Buffer fluid carried to the focusing junction envelopes an intersecting sample fluid, resulting in 3D focusing of the sample stream. The design requires four fluid ports and operates across a wide range of fluid velocities through pressure-driven flow. The focusing design was integrated with optical waveguides to interrogate fluorescing particles and confirm 3D focusing. Particle diffusion away from a focused stream was characterized.

更新日期：2019-12-11
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2018-05-05
Diane N H Kim,Kevin T Kim,Carolyn Kim,Michael A Teitell,Thomas A Zangle

Microfluidic devices are widely used for biomedical applications based on microscopy or other optical detection methods. However, the materials commonly used for microfabrication typically have a high refractive index relative to water, which can create artifacts at device edges and limit applicability to applications requiring high precision imaging or morphological feature detection. Here we present a soft lithography method to fabricate microfluidic devices out of MY133-V2000, a UV-curable, fluorinated polymer with low refractive index that is close to that of water (n = 1.33). The primary challenge in the use of this material (and fluorinated materials in general) is the low adhesion of the fluorinated material; we present several alternative fabrication methods we have tested to improve inter-layer adhesion. The close match between the refractive index of this material and aqueous solutions commonly used in biomedical applications enables fluorescence imaging at microchannel or other microfabricated edges without distortion. The close match in refractive index also enables quantitative phase microscopy (QPM) imaging across the full width of microchannels without error-inducing artifacts for measurement of cell biomass. Overall, our results demonstrate the utility of low-refractive index microfluidics for biological applications requiring high precision optical imaging.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2012-10-01
Taotao Zhu,Rui Cheng,Sarah A Lee,Eashwar Rajaraman,Mark A Eiteman,Troy D Querec,Elizabeth R Unger,Leidong Mao

A new sorting scheme based on ferrofluid hydrodynamics (ferrohydrodynamics) was used to separate mixtures of particles and live cells simultaneously. Two species of cells, including Escherichia coli and Saccharomyces cerevisiae, as well as fluorescent polystyrene microparticles were studied for their sorting throughput and efficiency. Ferrofluids are stable magnetic nanoparticles suspensions. Under external magnetic fields, magnetic buoyancy forces exerted on particles and cells lead to size-dependent deflections from their laminar flow paths and result in spatial separation. We report the design, modeling, fabrication and characterization of the sorting device. This scheme is simple, low-cost and label-free compared to other existing techniques.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2008-01-01
Holger Schmidt,Aaron R Hawkins

We review recent developments and current status of liquid-core optical waveguides in optofluidics with emphasis on suitability for creating fully planar optofluidic labs-on-a-chip. In this first of two contributions, we give an overview of the different waveguide types that are being considered for effectively combining micro and nanofluidics with integrated optics. The large number of approaches is separated into conventional index-guided waveguides and more recent implementations using wave interference. The underlying principle for waveguiding and the current status are described for each type. We then focus on reviewing recent work on microfabricated liquid-core antiresonant reflecting optical (ARROW) waveguides, including the development of intersecting 2D waveguide networks and optical fluorescence and Raman detection with planar beam geometry. Single molecule detection capability and addition of electrical control for electrokinetic manipulation and analysis of single bioparticles are demonstrated. The demonstrated performance of liquid-core ARROWs is representative of the potential of integrated waveguides for on-chip detection with ultrahigh sensitivity, and points the way towards the next generation of high-performance, low-cost and portable biomedical instruments.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2016-10-21

This study is motivated by the development of a blood cell filtration device for removal of malaria-infected, parasitized red blood cells (pRBCs). The blood was modeled as a multi-component fluid using the computational fluid dynamics discrete element method (CFD-DEM), wherein plasma was treated as a Newtonian fluid and the red blood cells (RBCs) were modeled as soft-sphere solid particles which move under the influence of drag, collisions with other RBCs, and a magnetic force. The CFD-DEM model was first validated by a comparison with experimental data from Han et al. 2006 (Han and Frazier 2006) involving a microfluidic magnetophoretic separator for paramagnetic deoxygenated blood cells. The computational model was then applied to a parametric study of a parallel-plate separator having hematocrit of 40% with a 10% of the RBCs as pRBCs. Specifically, we investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest. Simulations compared the efficacy of various geometries upon the stratification efficiency of the pRBCs. For a channel with nominal height of 100 µm, the addition of an upstream constriction of 80% improved the proportion of pRBCs retained adjacent to the magnetic wall (separation efficiency) by almost 2 fold, from 26% to 49%. Further addition of a downstream diffuser reduced remixing, hence improved separation efficiency to 72%. The constriction introduced a greater pressure drop (from 17 to 495 Pa), which should be considered when scaling-up this design for a clinical-sized system. Overall, the advantages of this design include its ability to accommodate physiological hematocrit and high throughput - which is critical for clinical implementation as a blood-filtration system.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-04-01
Clara Mata,Ellen Longmire,David McKenna,Katie Glass,Allison Hubel

The motion of cells in a two-stream microfluidic device designed to extract cryoprotective agents from cell suspensions was tested under a range of conditions. Jurkat cells (lymphoblasts) in a 10% dimethylsulfoxide solution were driven in parallel with phosphate-buffered saline solution wash streams through single rectangular channel sections and multiple sections in series. The influence of cell-stream flow rate and cell volume fraction (CVF) on cell viability and recovery were examined. The channel depth was 500 lm, and average cell stream velocity within the channels was varied from 3.6 to8.5 mm/s corresponding with cell stream Reynolds numbers of 2.6-6.0. Cell viability measured at device outlets was high for all cases examined indicating no significant cell damage within the device. Downstream of a single stage, cell recoveries measured 90-100% for average cell stream velocities ≥6 mm/s and for CVFs up to 20%. Cell recovery downstream of multistage devices also measured 90-100% after a critical device population time. This time was found to be five times the average cell residence time within the device. The measured recovery values were significantly larger than those typically obtained using conventional cell washing methods.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2017-01-01
Michael Frank,Dimitris Drikakis

The aim of this research is to identify possible mechanisms that govern heat transport at a solid-liquid interface using molecular dynamics. The study reveals that, unlike its bulk analogue, a liquid in a nanochannel sustains long-lived collective vibrations, phonons, which propagate over longer timescales and distances. The larger phonon mean free path in nanochannels is attributed to the greater structural order of the liquid atoms and to the larger liquid relaxation time-the time in which the liquid structure remains unchanged and solid-like. For channels of height less than 10 σ , long-range phonons are the dominant means of heat transfer in the directions parallel to the channel walls. The present findings are in agreement with experiments, which have observed significantly increased liquid relaxation times for the same range of channel heights. Finally, it is argued that confinement introduces additional transverse modes of vibration that also contribute to the thermal conductivity enhancement.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2017-05-01
Zhixing Zhang,Panita Maturavongsadit,Junyi Shang,Jing Yan,Dachao Li,Qian Wang,Qiao Lin

This paper presents a dielectric affinity microsensor that consists of an in situ prepared hydrogel attached to a pair of coplanar electrodes for dielectrically based affinity detection of glucose in subcutaneous tissue in continuous glucose monitoring applications. The hydrogel, incorporating N-3-acrylamidophenylboronic acid that recognizes glucose via affinity binding, is synthetically prepared on the electrodes via in situ gelation. When implanted in subcutaneous tissue, glucose molecules in interstitial fluid diffuse rapidly through the hydrogel and bind to the phenylboronic acid moieties. This induces a change in the hydrogel's permittivity and hence in the impedance between the electrodes, which can be measured to determine the glucose concentration. The in situ hydrogel preparation allows for a reduced hydrogel thickness (~10 μm) to enable the device to respond rapidly to glucose concentration changes in tissue, as well as covalent electrode attachment of the hydrogel to eliminate the need for semipermeable membranes that would otherwise be required to restrain the sensing material within the device. Meanwhile, the use of coplanar electrodes is amenable to the in situ preparation and facilitates glucose accessibility of the hydrogel, and combined with dielectrically based transduction, also eliminates mechanical moving parts often found in existing affinity glucose microsensors that can be fragile and complicated to fabricate. Testing of the device in phosphate-buffered saline at pH 7.4 and 37 °C has shown that at glucose concentrations ranging from 0 to 500 mg/dL, the hydrogel-based microsensor exhibits a rapid, repeatable, and reversible response. In particular, in the glucose concentration range of 40-100 mg/dL, which is of great clinical interest to monitoring normal and low blood sugar levels, the device response is approximately linear with a resolution of 0.32 mg/dL based on effective capacitance and 0.27 mg/dL based on effective resistance, respectively. Thus, the device holds the potential to enable reliable and accurate continuous monitoring of glucose in subcutaneous tissue.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2015-10-01
John P Hilton,Timothy Olsen,Jinho Kim,Jing Zhu,ThaiHuu Nguyen,Mihaela Barbu,Renjun Pei,Milan Stojanovic,Qiao Lin

This paper presents a microfluidic chip capable of isolating thermally sensitive protein-binding aptamer candidates. The chip makes use of bead-immobilized target molecules and DNA (deoxyribonucleic acid) sequences to enable a simplified chip design, in which affinity selection and PCR (polymerase chain reaction) amplification of target-binding sequences occur in temperature-controlled microchambers. Using pressure-driven flow, buffer containing single-stranded DNA molecules with randomized sequences is cycled through a series of affinity selection and PCR amplification steps on microbeads. Successive introduction of the sample to each chamber effects a process of competition whereby DNA strands with weak binding strength to target molecules are rejected in favor of strongly binding sequences. Using bead-based PCR, the amplification step was miniaturized and integrated with affinity selection, resulting in significant reductions in process time and reagent use. As a demonstration, temperature-dependent selection and amplification of single-stranded oligonucleotides that bind to human Immuno-globulin E (IgE) was performed in 4 h, a 20-fold reduction in process time as compared to conventional methods that would require approximately a week. Fluorescent binding assays then demonstrated that the desired temperature specificity was imparted to the aptamer candidates within just one round of selection, and within two rounds the aptamer candidates exhibited enhanced affinity toward IgE.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2018-01-01
David Stephenson,James R Kermode,Duncan A Lockerby

We present a scheme for accelerating hybrid continuum-atomistic models in multiscale fluidic systems by using Gaussian process regression as a surrogate model for computationally expensive molecular dynamics simulations. Using Gaussian process regression, we are able to accurately predict atomic-scale information purely by consideration of the macroscopic continuum-model inputs and outputs and judge on the fly whether the uncertainty of our prediction is at an acceptable level, else a new molecular simulation is performed to continually augment the database, which is never required to be complete. This provides a substantial improvement over the current generation of hybrid methods, which often require many similar atomistic simulations to be performed, discarding information after it is used once. We apply our hybrid scheme to nano-confined unsteady flow through a high-aspect-ratio converging-diverging channel, and make comparisons between the new scheme and full molecular dynamics simulations for a range of uncertainty thresholds and initial databases. For low thresholds, our hybrid solution is highly accurate-around that of thermal noise. As the uncertainty threshold is raised, the accuracy of our scheme decreases and the computational speed-up increases (relative to a full molecular simulation), enabling the compromise between accuracy and efficiency to be tuned. The speed-up of our hybrid solution ranges from an order of magnitude, with no initial database, to cases where an extensive initial database ensures no new MD simulations are required.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2018-01-01
Lyes Kahouadji,Emilia Nowak,Nina Kovalchuk,Jalel Chergui,Damir Juric,Seungwon Shin,Mark J H Simmons,Richard V Craster,Omar K Matar

The three-dimensional two-phase flow dynamics inside a microfluidic device of complex geometry is simulated using a parallel, hybrid front-tracking/level-set solver. The numerical framework employed circumvents numerous meshing issues normally associated with constructing complex geometries within typical computational fluid dynamics packages. The device considered in the present work is constructed via a module that defines solid objects by means of a static distance function. The construction combines primitive objects, such as a cylinder, a plane, and a torus, for instance, using simple geometrical operations. The numerical solutions predicted encompass dripping and jetting, and transitions in flow patterns are observed featuring the formation of drops, 'pancakes', plugs, and jets, over a wide range of flow rate ratios. We demonstrate the fact that vortex formation accompanies the development of certain flow patterns, and elucidate its role in their underlying mechanisms. Experimental visualisation with a high-speed imaging are also carried out. The numerical predictions are in excellent agreement with the experimental data.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2017-09-01
Amir Ghasemi,Hamed Amiri,Hossein Zare,Maryam Masroor,Akbar Hasanzadeh,Ali Beyzavi,Amir R Aref,Mahdi Karimi,Michael R Hamblin

Advanced nanomaterials such as carbon nano-tubes (CNTs) display unprecedented properties such as strength, electrical conductance, thermal stability, and intriguing optical properties. These properties of CNT allow construction of small microfluidic devices leading to miniaturization of analyses previously conducted on a laboratory bench. With dimensions of only millimeters to a few square centimeters, these devices are called lab-on-a-chip (LOC). A LOC device requires a multidisciplinary contribution from different fields and offers automation, portability, and high-throughput screening along with a significant reduction in reagent consumption. Today, CNT can play a vital role in many parts of a LOC such as membrane channels, sensors and channel walls. This review paper provides an overview of recent trends in the use of CNT in LOC devices and covers challenges and recent advances in the field. CNTs are also reviewed in terms of synthesis, integration techniques, functionalization and superhydrophobicity. In addition, the toxicity of these nanomaterials is reviewed as a major challenge and recent approaches addressing this issue are discussed.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2018-01-01
Bram Bet,Rumen Georgiev,William Uspal,Huseyin Burak Eral,René van Roij,Sela Samin

We combine theory and numerical calculations to accurately predict the motion of anisotropic particles in shallow microfluidic channels, in which the particles are strongly confined in the vertical direction. We formulate an effective quasi-two-dimensional description of the Stokes flow around the particle via the Brinkman equation, which can be solved in a time that is two orders of magnitude faster than the three-dimensional problem. The computational speedup enables us to calculate the full trajectories of particles in the channel. To validate our scheme, we study the motion of dumbbell-shaped particles that are produced in a microfluidic channel using 'continuous-flow lithography'. Contrary to what was reported in earlier work (Uspal et al. in Nat Commun 4:2666, 2013), we find that the reorientation time of a dumbbell particle in an external flow exhibits a minimum as a function of its disk size ratio. This finding is in excellent agreement with new experiments, thus confirming the predictive power of our scheme.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2018-01-01
Davide Caprini,Giorgia Sinibaldi,Luca Marino,Carlo Massimo Casciola

A novel design for the classical microfluidic device known as T-junction is proposed with the purpose of obtaining a simultaneous measurement of the in-plane velocity components in two orthogonal planes. A crucial feature of the proposed configuration is that all three velocity components are available along the intersection of the two planes. A dedicated optical set-up is developed to convey the two simultaneous views from the orthogonal planes into the sensor of a single camera, where a compound image is formed showing on either half one of the two views. A commercial micro-particle image velocimetry system is used to measure the velocity in the two planes. Feeding the T-junction with a liquid continuous phase and a dispersed gas phase, the velocity is measured by phase averaging along the bubble formation and break-up process showing the potentialities of the new design. The accuracy analysis shows that the error is dominated by a systematic component due to the thickness of the measurement slice. The error can be reduced by applying confocal microscopy to the present system with no further modifications so as to reduce the thickness of the measurement slab thereby reducing the error. Moreover, by sweeping the planes across the region of interest, a full three-dimensional reconstruction of the velocity field can be readily obtained. Finally, the simultaneous views offer the possibility to extract the principal curvatures of the bubble meniscus thereby providing access to the Laplace pressure.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2013-02-27
Ali Haider Dhanaliwala,Johnny L Chen,Shiying Wang,John A Hossack

Current microbubble-based ultrasound contrast agents are administered intravenously resulting in large losses of contrast agent, systemic distribution, and strict requirements for microbubble longevity and diameter size. Instead we propose in situ production of microbubbles directly within the vasculature to avoid these limitations. Flow focusing microfluidic devices (FFMDs) are a promising technology for enabling in situ production as they can produce microbubbles with precisely controlled diameters in real-time. While the microfluidic chips are small, the addition of inlets and interconnects to supply the gas and liquid phase greatly increases the footprint of these devices preventing the miniaturization of FFMDs to sizes compatible with medium and small vessels. To overcome this challenge, we introduce a new method for supplying the liquid (shell) phase to an FFMD that eliminates bulky interconnects. A pressurized liquid-filled chamber is coupled to the liquid inlets of an FFMD, which we term a flooded FFMD. The microbubble diameter and production rate of flooded FFMDs were measured optically over a range of gas pressures and liquid flow rates. The smallest FFMD manufactured measured 14.5 × 2.8 × 2.3 mm. A minimum microbubble diameter of 8.1 ± 0.3 μm was achieved at a production rate of 450,000 microbubbles/s (MB/s). This represents a significant improvement with respect to any previously reported result. The flooded design also simplifies parallelization and production rates of up to 670,000 MB/s were achieved using a parallelized version of the flooded FFMD. In addition, an intravascular ultrasound (IVUS) catheter was coupled to the flooded FFMD to produce an integrated ultrasound contrast imaging device. B-mode and IVUS images of microbubbles produced from a flooded FFMD in a gelatin phantom vessel were acquired to demonstrate the potential of in situ microbubble production and real-time imaging. Microbubble production rates of 222,000 MB/s from a flooded FFMD within the vessel lumen provided a 23 dB increase in B-mode contrast. Overall, the flooded design is a critical contribution towards the long- term goal of utilizing in situ produced microbubbles for contrast enhanced ultrasound imaging of, and drug delivery to, the vasculature.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2018-12-18
Chaojun Cheng,Ankitha Rajagopalan Nair,Raviraj Thakur,Gene Fridman

Various microfluidic architectures designed for in vivo and point-of-care diagnostic applications require larger channels, autonomous actuation, and portability. In this paper, we present a normally closed microvalve design capable of fully autonomous actuation for wide diameter microchannels (tens to hundreds of μm). We fabricated the multilayer plunger-membrane valve architecture using the silicone elastomer, poly-dimethylsiloxane (PDMS) and optimized it to reduce the force required to open the valve. A 50-μm Nitinol (NiTi) shape memory alloy wire is incorporated into the device and can operate the valve when actuated with 100-mA current delivered from a 3-V supply. We characterized the valve for its actuation kinetics using an electrochemical assay and tested its reliability at 1.5-s cycle duration for 1 million cycles during which we observed no operational degradation.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2007-07-19
Aaron R Hawkins,Holger Schmidt

We review fabrication methods and common structures for optofluidic waveguides, defined as structures capable of optical confinement and transmission through fluid filled cores. Cited structures include those based on total internal reflection, metallic coatings, and interference based confinement. Configurations include optical fibers and waveguides fabricated on flat substrates (integrated waveguides). Some examples of optofluidic waveguides that are included in this review are Photonic Crystal Fibers (PCFs) and two-dimensional photonic crystal arrays, Bragg fibers and waveguides, and Anti Resonant Reflecting Optical Waveguides (ARROWs). An emphasis is placed on integrated ARROWs fabricated using a thin-film deposition process, which illustrates how optofluidic waveguides can be combined with other microfluidic elements in the creation of lab-on-a-chip devices.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2008-10-01
Yevgeniy Kalinin,Viatcheslav Berejnov,Robert E Thorne

Photolithographic micropatterning is used to achieve topographic rather than chemical control of the static shape and position of microdrops on solid substrates in a gaseous ambient. Micrometer cross-section, millimeter-diameter circular rings with steep sidewalls strongly and robustly pin contact lines of nanoliter to 100 microliter liquid drops, increasing the maximum stable drop volume and eliminating contact line motion due to transient accelerations. Physical and chemical processes involving two-phase transport within these drops are more reproducible, and automated image analysis of the evolving drop contents is greatly simplified. This technique has particular promise for high-throughput protein solution screening in structural genomics and drug discovery.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-10-19
Jeong Hoon Lee,Jongyoon Han

Here, we report a new method of concentration-enhanced binding kinetics for a rapid immunoassay screening test on a gold surface in a poly(dimethylsiloxane) (PDMS) microfluidic chip format. The use of alkylthiolate self-assembled monolayers on gold surfaces of a PDMS-glass microchip resulted in accelerated binding kinetics of Human chorionic gonadotropin (hCG) at an electrokinetic trapping zone. We used a PBS solution (buffer concentration ~ 150 mM), not a dibasic buffer system (~10 mM), for the dynamic preconcentrating operation and the preconcentration of cy3 labeled streptavidin onto biotinylated Au surface revealed that the binding kinetics of the protein were linearly proportional to the concentration profile of the preconcentration plug. We showed rapid detection of hCG in the clinical range with a shorten assay time of 10 min. Also, we demonstrated that the amount of sample needed were detection was decreased from ~4 mL to ~25 μL in the standard serum tests. The enhanced binding kinetics between hcG Ag-Ab via preconcentration showed good feasibility for use in a rapid immunoassay screening test.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-10-13
Dustin S Chang,Sean M Langelier,Ramsey I Zeitoun,Mark A Burns

Pressure-driven flow control systems are a critical component in many microfluidic devices. Compartmentalization of this functionality into a stand-alone module possessing a simple interface would allow reduction of the number of pneumatic interconnects required for fluidic control. Ideally, such a module would also be sufficiently compact for implementation in portable platforms. In our current work, we show the feasibility of using a modular array of Venturi pressure microregulators for coordinated droplet manipulation. The arrayed microregulators share a single pressure input and are capable of outputting electronically controlled pressures that can be independently set between ±1.3 kPa. Because the Venturi microregulator operates by thermal perturbation of a choked gas flow, this output range corresponds to a temperature variation between 20 and 95°C. Using the array, we demonstrate loading, splitting, merging, and independent movement of multiple droplets in a valveless microchannel network.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-10-12
Kan Liu,Yi-Chun Chen,Hsian-Rong Tseng,Clifton Kwang-Fu Shen,R Michael van Dam

Using liquid slugs as microreactors and microvessels enable precise control over the conditions of their contents on short-time scales for a wide variety of applications. Particularly for screening applications, there is a need for control of slug parameters such as size and composition. We describe a new microfluidic approach for creating slugs in air, each comprising a size and composition that can be selected individually for each slug. Two-component slugs are formed by first metering the desired volume of each reagent, merging the two volumes into an end-to-end slug, and propelling the slug to induce mixing. Volume control is achieved by a novel mechanism: two closed chambers on the chip are initially filled with air, and a valve in each is briefly opened to admit one of the reagents. The pressure of each reagent can be individually selected and determines the amount of air compression, and thus the amount of liquid that is admitted into each chamber. We describe the theory of operation, characterize the slug generation chip, and demonstrate the creation of slugs of different compositions. The use of microvalves in this approach enables robust operation with different liquids, and also enables one to work with extremely small samples, even down to a few slug volumes. The latter is important for applications involving precious reagents such as optimizing the reaction conditions for radiolabeling biological molecules as tracers for positron emission tomography. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10404-010-0617-0) contains supplementary material, which is available to authorized users.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-10-12
Daniele Malleo,J Tanner Nevill,Luke P Lee,Hywel Morgan

A device for continuous differential impedance analysis of single cells held by a hydrodynamic cell trapping is presented. Measurements are accomplished by recording the current from two closely-situated electrode pairs, one empty (reference) and one containing a cell. We demonstrate time-dependent measurement of single cell impedance produced in response to dynamic chemical perturbations. First, the system is used to assay the response of HeLa cells to the effects of the surfactant Tween, which reduces the impedance of the trapped cells in a concentration dependent way and is interpreted as gradual lysis of the cell membrane. Second, the effects of the bacterial pore-forming toxin, Streptolysin-O are measured: a transient exponential decay in the impedance is recorded as the cell membrane becomes increasingly permeable. The decay time constant is inversely proportional to toxin concentration (482, 150, and 30 s for 0.1, 1, and 10 kU/ml, respectively). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10404-009-0534-2) contains supplementary material, which is available to authorized users.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-08-10
Lawrence A Sasso,Akif Undar,Jeffrey D Zahn

This article presents a microfluidic device which integrates autonomous serial immunofluorocytometry binding reactions of cytometric beads with fluorescence detection and quantification in a continuous flow environment. The microdevice assay is intended to alleviate the extensive benchwork and large sample volumes used when conducting traditional immunoassays, without requiring complex external controls. The technology is based on the miniaturization and automation of the serial processing steps of an antigen sandwich immunoassay, with integrated fluorescence detection using paramagnetic microbeads. The continuous flow design may enable temporal tracking of time-varying protein concentrations in a continuously infused sample for clinical applications, specifically for monitoring inflammation marker proteins in blood produced during cardiac surgeries involving cardiopulmonary bypass (CPB) procedures. The device operation was first validated via a single incubation device which measured the concentration of a fluorescently labeled biotin molecule using streptavidin-coated paramagnetic cytometric beads. Subsequently, a dual incubation device was tested with samples of the anaphylatoxin complement protein C3a, and was shown to be capable of differentiating between samples at typical systemic concentrations of the protein (1-5 mug/ml), with very low sample usage (<6 mul/h). It is believed that this continuous flow, automated microimmunosensor technology will be a platform for high sample rate immunoassays capable of tracking and more thoroughly characterizing the systemic inflammation process, and may aid in the development of better treatment options for systemic inflammation during and after CPB.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-05-18
Liang Li,Qiang Fu,Christopher A Kors,Lance Stewart,Peter Nollert,Philip D Laible,Rustem F Ismagilov

This paper presents a plug-based microfluidic system to dispense nanoliter-volume plugs of Lipidic Cubic Phase (LCP) material and subsequently merge the LCP plugs with aqueous plugs. This system was validated by crystallizing membrane proteins in lipidic mesophases, including LCP. This system allows for accurate dispensing of LCP material in nanoliter volumes, prevents inadvertent phase transitions that may occur due to dehydration by enclosing LCP in plugs, and is compatible with the traditional method of forming LCP material using a membrane protein sample, as shown by the successful crystallization of bacteriorhodopsin from Halobacterium salinarum. Conditions for the formation of LCP plugs were characterized and presented in a phase diagram. This system was also implemented using two different methods of introducing the membrane protein: 1) the traditional method of generating the LCP material using a membrane protein sample and 2) Post LCP-formation Incorporation (PLI), which involves making LCP material without protein, adding the membrane protein sample externally to the LCP material, and allowing the protein to diffuse into the LCP material or into other lipidic mesophases that may result from phase transitions. Crystals of bacterial photosynthetic reaction centers from Rhodobacter sphaeroides and Blastochloris viridis were obtained using PLI. The plug-based, LCP-assisted microfluidic system, combined with the PLI method for introducing membrane protein into LCP, should be useful for minimizing consumption of samples and broadening the screening of parameter space in membrane protein crystallization.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-04-02
Ieong Wong,Chih-Ming Ho

Fast advancements of microfabrication processes in past two decades have reached to a fairly matured stage that we can manufacture a wide range of microfluidic devices. At present, the main challenge is the control of nanoscale properties on the surface of lab-on-a-chip to satisfy the need for biomedical applications. For example, poly(dimethylsiloxane) (PDMS) is a commonly used material for microfluidic circuitry, yet the hydrophobic nature of PDMS surface suffers serious nonspecific protein adsorption. Thus the current major efforts are focused on surface molecular property treatments for satisfying specific needs in handling macro functional molecules. Reviewing surface modifications of all types of materials used in microfluidics will be too broad. This review will only summarize recent advances in nonbiofouling PDMS surface modification strategies applicable to microfluidic technology and classify them into two main categories: (1) physical approach including physisorption of charged or amphiphilic polymers and copolymers, as well as (2) chemical approach including self assembled monolayer and thick polymer coating. Pros and cons of a collection of available yet fully exploited surface modification methods are briefly compared among subcategories.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-03-31
Joong Yull Park,Mina Morgan,Aaron N Sachs,Julia Samorezov,Ryan Teller,Ye Shen,Kenneth J Pienta,Shuichi Takayama

Conventional cell trapping methods using microwells with small dimensions (10-20 μm) are useful for examining the instantaneous cell response to reagents; however, such wells have insufficient space for longer duration screening tests that require observation of cell attachment and division. Here we describe a flow method that enables single cell trapping in microwells with dimensions of 50 μm, a size sufficient to allow attachment and division of captured cells. Among various geometries tested, triangular microwells were found to be most efficient for single cell trapping while providing ample space for cells to grow and spread. An important trapping mechanism is the formation of fluid streamlines inside, rather than over, the microwells. A strong flow recirculation occurs in the triangular microwell so that it efficiently catches cells. Once a cell is captured, the cell presence in the microwell changes the flow pattern, thereby preventing trapping of other cells. About 62% of microwells were filled with single cells after a 20 min loading procedure. Human prostate cancer cells (PC3) were used for validation of our system.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-02-04
Xiayan Wang,Chang Cheng,Shili Wang,Shaorong Liu

Electroosmotic pumping is receiving increasing attention in recent years owing to the rapid development in micro total analytical systems. Compared with other micropumps, electroosmotic pumps (EOPs) offer a number of advantages such as creation of constant pulse-free flows and elimination of moving parts. The flow rates and pumping pressures of EOPs matches well with micro analysis systems. The common materials and fabrication technologies make it readily integrateable with lab-on-a-chip devices. This paper reviews the recent progress on EOP fabrications and applications in order to promote the awareness of EOPs to researchers interested in using micro- and nano-fluidic devices. The pros and cons of EOPs are also discussed, which helps these researchers in designing and constructing their micro platforms.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2008-09-23
David Erickson,Sudeep Mandal,Allen H J Yang,Bernardo Cordovez

Next generation biosensor platforms will require significant improvements in sensitivity, specificity and parallelity in order to meet the future needs of a variety of fields ranging from in vitro medical diagnostics, pharmaceutical discovery and pathogen detection. Nano-biosensors, which exploit some fundamental nanoscopic effect in order to detect a specific biomolecular interaction, have now been developed to a point where it is possible to determine in what cases their inherent advantages over traditional techniques (such as nucleic acid microarrays) more than offset the added complexity and cost involved constructing and assembling the devices. In this paper we will review the state of the art in nanoscale biosensor technologies, focusing primarily on optofluidic type devices but also covering those which exploit fundamental mechanical and electrical transduction mechanisms. A detailed overview of next generation requirements is presented yielding a series of metrics (namely limit of detection, multiplexibility, measurement limitations, and ease of fabrication/assembly) against which the various technologies are evaluated. Concluding remarks regarding the likely technological impact of some of the promising technologies are also provided.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2014-01-21
Yi Wang,Hongjun Song,Kapil Pant

This paper presents a Krylov subspace projection-based Reduced Order Model (ROM) for whole microfluidic chip thermal analysis, including conjugate heat transfer. Two key steps in the reduced order modeling procedure are described in detail, including (1) the acquisition of a 3D full-scale computational model in the state-space form to capture the dynamic thermal behavior of the entire microfluidic chip; and (2) the model order reduction using the Block Arnoldi algorithm to markedly lower the dimension of the full-scale model. Case studies using practically relevant thermal microfluidic chip are undertaken to establish the capability and to evaluate the computational performance of the reduced order modeling technique. The ROM is compared against the full-scale model and exhibits good agreement in spatiotemporal thermal profiles (<0.5% relative error in pertinent time scales) and over three orders-of-magnitude acceleration in computational speed. The salient model reusability and real-time simulation capability renders it amenable for operational optimization and in-line thermal control and management of microfluidic systems and devices.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2014-01-18
Ahmed M Amin,Raviraj Thakur,Seth Madren,Han-Sheng Chuang,Mithuna Thottethodi,T N Vijaykumar,Steven T Wereley,Stephen C Jacobson

Current lab-on-a-chip (LoC) devices are assay-specific and are custom-built for each single experiment. Performing an experiment requires scientists or engineers to go through the time-consuming process of designing, fabricating, and testing a chip before conducting the actual experiment. This prolonged cycle can take months to complete, increasing effort and cost and reducing productivity. Similarly, minor modifications to an assay protocol re-incur the overheads of the design cycle. In this paper, we develop a multi-purpose, software-programmableLab-on-a-Chip (SPLoC), where the user simply writes or downloads a program for each experiment. We describe the components necessary to realize the SPLoC, which include a high-level programming language, an abstract instruction set, a runtime and control system, and a microfluidic device. We describe two key features of our high-level language compiler, and describe a novel variable-volume variable-ratio mixer. Finally, we demonstrate our SPLoC on four diverse, real-world assays.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2013-11-19
Xinyu Zhang,Raghuram Dhumpa,Michael G Roper

Stimulation of cells with temporal waveforms can be used to observe the frequency-dependent nature of cellular responses. The ability to produce and maintain the temporal waveforms in spite of the broadening processes that occur as the wave travels through the microfluidic system is critical for observing dynamic behaviors. Broadening of waves in microfluidic channels has been examined, but the effect that large-volume cell chambers have on the waves has not. In this report, a sinusoidal glucose wave delivered to a 1 mm diameter cell chamber using various microfluidic channel structures was simulated by finite element analysis with the goal of minimizing the broadening of the waveform in the chamber and maximizing the homogeneity of the concentration in the chamber at any given time. Simulation results indicated that increasing the flow rate was the most effective means to achieve these goals, but at a given volumetric flow rate, geometries that deliver the waveform to multiple regions in the chamber while maintaining a high linear velocity produced sufficient results. A 4-inlet geometry with a 220 μm channel width gave the best result in the simulation and was used to deliver glucose waveforms to a population of pancreatic islets of Langerhans. The result was a stronger and more robust synchronization of the islet population as compared to when a non-optimized chamber was used. This general strategy will be useful in other microfluidic systems examining the frequency-dependence nature of cellular behavior.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2013-11-05
Jian Zhou,Susan Kasper,Ian Papautsky

Inertial microfluidics has been attracting considerable interest for size-based separation of particles and cells. The inertial forces can be manipulated by expanding the microchannel geometry, leading to formation of microvortices which selectively isolate and trap particles or cells from a mixture. In this work, we aim to enhance our understanding of particle trapping in such microvortices by developing a model of selective particle trapping. Design and operational parameters including flow conditions, size of the trapping region, and target particle concentration are explored to elucidate their influence on trapping behavior. Our results show that the size dependence of trapping is characterized by a threshold Reynolds number, which governs the selective entry of particles into microvortices from the main flow. We show that concentration enhancement on the order of 100,000× and isolation of targets at concentrations in the 1/mL is possible. Ultimately, the insights gained from our systematic investigation suggest optimization solutions that enhance device performance (efficiency, size selectivity, and yield) and are applicable to selective isolation and trapping of large rare cells as well as other applications.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2013-08-13
Xuefei Sun,Keqi Tang,Richard D Smith,Ryan T Kelly

We present an integrated droplet-on-demand microfluidic platform for dispensing, mixing, incubating, extracting and analyzing by mass spectrometry pico- to nanoliter-sized droplets. All of the functional components are successfully integrated for the first time into a monolithic microdevice. Droplet generation is accomplished using computer-controlled pneumatic valves. Controlled actuation of valves for different aqueous streams enables accurate dosing and rapid mixing of reagents within droplets in either the droplet generation area or in a region of widening channel cross-section. Following incubation, which takes place as droplets travel in the oil stream, the droplet contents are extracted to an aqueous channel for subsequent ionization at an integrated nanoelectrospray emitter. Using the integrated platform, rapid enzymatic digestions of a model protein were carried out in droplets and detected on-line by nanoelectrospray ionization mass spectrometry.

更新日期：2019-11-01
• Microfluid. Nanofluid. (IF 2.437) Pub Date : 2010-10-01
Amy L McPherson,Glenn M Walker

A microfluidic device using on-chip passive pumping was characterized for use as a particle counter. Flow occurred due to a Young-Laplace pressure gradient between two 1.2 mm diameter inlets and a 4 mm diameter reservoir when 0.5μ L fluid droplets were applied to the inlets using a micropipette. Polystyrene particles (10μm diameter) were enumerated using the resistive pulse technique. Particle counts using passive pumping were within 13% of counts from a device using syringe pumping. All pumping methods produced particle counts that were within 16% of those obtained with a hemocytometer. The effect of intermediate wash steps on particle counts within the passive pumping device was determined. Zero, one, or two wash droplets were loaded after the first of two sample droplets. No statistical difference was detected in the mean particle counts among the loading patterns (p > 0.05). Hydrodynamic focusing using passive pumping was also demonstrated.

更新日期：2019-11-01
Contents have been reproduced by permission of the publishers.

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