Microfluidics and Nanofluidics

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 field gradients, 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.

An integrated thermofluidic analysis of DNA hybridization, in the presence of combined electrokinetically and/or pressure-driven microchannel flows, is presented in this work. A comprehensive model is developed that combines bulk and surface transport of momentum, heat and solute with the pertinent hybridization kinetics, in a detailed manner. Results confirm that electrokinetic accumulation of DNA occurs within a few seconds or minutes, as compared to passive hybridization that could sometimes take several hours. Further, it is observed that by increasing the accumulation time, significantly higher concentration of DNA can be achieved at the capture probes. However, this eventually tends to attain a saturation state, due to a lesser probability of successful hybridization on account of a prior accumulation of target DNA molecules on the capture probe strands. While favorable pressure gradients augment DNA hybridization rates that are otherwise established by the electro-osmotic transport, adverse pressure gradients of comparable magnitude may turn out to be much less consequential in retarding the same. Such effects can be of potential significance in the designing of a microfluidic arrangement to achieve the fastest rate of DNA hybridization.

This study raises doubts about some fundamental ideas of electrostatics, namely the uniqueness theorems. The Poisson-Boltzmann equation (PBE) gives us very simple formula for charge density distribution (ρe) within fluids. Here we show that the old boundary conditions (BC), which are usually used to solve PBE, have serious defects. For example, Dirichlet condition (DC) assigns values to electrostatic potential (ψ) at different boundaries in an absolute sense i.e. without specifying any reference, which is meaningless and leads to violation of charge conservation principle. The Neumann condition (NC) assigns 'independent' values to ψ at different boundaries, whereas they are actually 'related' to each other through Poisson's equation in electrostatics (PES), which makes the solutions non-unique. We use BCs of mixed type to derive correct formula for ρe that addresses the above defects. A remarkable conclusion follows: the present physical interpretation of 'Debye length' (λD) as a screening length is incorrect.

We report a simple low-cost magnetic microfluidic device for magnetic bead separation and immobilisation. One dimensional arrays of localised high magnetic field gradients are constructed at the interfaces between regions magnetised with opposing polarities on the magnetic Fe 2 O 3 composite stripes of credit cards. The localised high magnetic field gradients are employed to trap magnetic beads on the surface of the magnetic stripe, without the need for external magnetic components. A magnetic card writer was used to deterministically pattern the magnetic stripes of credit cards to define arrays of magnetic reversals. The fabrication of the device is based on PDMS to credit card bonding of simple flow channels. Experimental results demonstrate that magnetic beads can be captured with efficiencies of 85 %, 67 % and 27 % at flow rates of 25 µlmin -1 , 50 µlmin -1 and 100 µlmin -1 respectively. The results show that the credit card-based magnetic separator might offer an efficient, simple, low-cost alternative to traditional microfluidic magnetic separators for applications such as immunomagnetic cell separation.

This paper introduces a passive degassing mechanism using textured surfaces to trap and transport bubbles, and then using hydrophobic porous membranes to vent out bubbles in a microfluidic system. The bubble trapping ability is achieved by creating nanostructures to promote bubble nucleation and coalescence on the sidewalls of KOH-etched concave pits in a silicon substrate. The substrate, which is bonded with a porous membrane, is placed in a liquid system with chemically generated CO 2 bubbles to examine the degassing ability. The results validate that the bubbles can be easily trapped on the surfaces with nanostructures, and then vented through the porous membrane. Our proposed approach possesses the advantage of simple fabrication, great structure robustness, and effective bubble trapping and removing abilities, which show their great potential as economic, passive means of preventing the gas byproducts from blocking surfaces and improving the efficiency of microfluidic systems during operations.

Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.

Thermoplastics are highly attractive substrate materials for microfluidic systems, with important benefits in the development of low cost disposable devices for a host of bioanalytical applications. While significant research activity has been directed towards the formation of microfluidic components in a wide range of thermoplastics, sealing of these components is required for the formation of enclosed microchannels and other microfluidic

Starting from the background of nanofluidics in other disciplines, this paper describes the present state of research in this field and discusses possible directions of development. Emphasis is put on the very diverse background of nanofluidics in biology, chemistry, physics and engineering and the valuable knowledge available in these disciplines. First, the forces that play a role on the nanoscale are discussed and then a summary is given of some different theoretical treatments. Subsequently, an overview is given of the different phenomena occurring on the nanoscale and their present applications. Finally, some possible future applications are discussed.

Cyclic olefin polymers (COPs) are increasingly popular as substrate material for microfluidics. This is due to their promising properties, such as high chemical resistance, low water absorption, good optical transparency in the near UV range and ease of fabrication. COPs are commercially available from a range of manufacturers under various brand names (Apel, Arton, Topas, Zeonex and Zeonor). Some of these (Apel and Topas) are made from more than one kind of monomer and therefore also known as cyclic olefin copolymers (COCs). In order to structure these materials, a wide array of fabrication methods is available. Laser ablation and micromilling are direct structuring methods suitable for fast prototyping, whilst injection moulding, hot embossing and nanoimprint lithography are replication methods more appropriate for low-cost production. Using these fabrication methods, a multitude of chemical analysis techniques have already been implemented. These include microchip electrophoresis (MCE), chromatography, solid phase extraction (SPE), isoelectric focusing (IEF) and mass spectrometry (MS). Still much additional work is needed to characterise and utilise the full potential of COP materials. This is especially true within optofluidics, where COPs are still rarely used, despite their excellent optical properties. This review presents a detailed description of the properties of COPs, the available fabrication methods and several selected applications described in the literature.

Nanotubes and nanowires have sparked considerable interest in biosensing applications due to their exceptional charge transport properties and size compatibility with biomolecules. Among the various biosensing methodologies incorporating these nanostructured materials in their sensing platforms, liquid-gated field-effect transistors (LGFETs)-based device configurations outperform the conventional electrochemical measurements by their ability in providing label free, direct electronic read-out, and real-time detection. Together with integration of a microfluidic channel into the device architecture, nanotube- or nanowires-based LGFET biosensor have demonstrated promising potential toward the realization of truly field-deployable self-contained lab-on-chip devices, which aim to complement the existing lab-based methodologies. This review addresses the recent advances in microfluidic-integrated carbon nanotubes and inorganic nanowires-based LGFET biosensors inclusive of nanomaterials growth, device fabrication, sensing mechanisms, and interaction of biomolecules with nanotubes and nanowires. Design considerations, factors affecting sensing performance and sensitivity, amplification and multiplexing strategies are also detailed to provide a comprehensive understanding of present biosensors and future sensor systems development.

Nowadays, nanoparticles have been widely applied in liquids due to their great impact on the growth rate of heat transfer as well as the solutions for the problems raised from the use of particles larger than nano in various currents. Therefore, in this article, an attempt has been made to study the research carried out in the field of forced heat transfer of nanofluids inside channels and pipes. In this way, the authors are reviewing articles starting from 2018 for channels and 2017 for tubes/pipes. All the articles that are in the above category have been studied from different viewpoints. In this article, first, the type of flow and the relations used in this field are introduced and by comparing the published articles in terms of methodology, type and size of nanoparticles, volumetric ratios of nanoparticles, flow conditions, etc., so that the effect of these parameters can be studied on heat transfer. The following is a statistical study of articles in this field, which includes all articles published from the beginning to the present, which have dealt with this issue in theory, numerical and experimental. As a result, it becomes clear that the special geometric properties of channels and pipes, the insertion of obstacles in the flow path with special conditions and characteristics, as well as the boundary conditions defined in recent studies have considerable influence on the growth of heat transfer rate and the improvement of system efficiency.

Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.

Electrochemical techniques are widely used in microfluidic and nanofluidic devices because they are suitable for miniaturization, have better sensitivity compared to optical detection techniques, and their components can be reliably microfabricated. In addition to the detection and quantification of analytes, electrochemical techniques can be used to monitor processes such as biological cell death and protein/DNA separations/purifications. Such techniques are combined with micro-and nanofluidic devices with point-of-care (POC) applications in mind, where cost, footprint, ease of use, and independence from peripheral equipment are critical for a viable design. A large variety of electrode materials and device configurations have been employed to meet these requirements. This review introduces the reader to the major electrochemical techniques, materials, and fabrication methods for working and reference electrodes, and to surface modifications of electrodes to facilitate electrochemical measurements, in the context of micro-and nanofluidic devices. The continuing development of these techniques holds promise for the next-generation lab-on-a-chip devices, which can realize the goals of this technology such as POC clinical analysis.

We report the results of a comparative study of microfluidic emulsification of liquids with different viscosities. Depending on the properties of the fluids and their rates of flow, emulsification occurred in the dripping and jetting regimes. We studied the characteristic features and typical dependence of the size and of the size distribution of droplets in each regime. For each liquid, we identified a range of hydrodynamic conditions promoting generation of highly monodisperse droplets. Viscosity played an important role in emulsification: highly viscous liquids were emulsified into larger droplets with lower polydispersity. Although it was not possible to provide a unified scaling for the volumes of the droplets, our results suggest that the break-up dynamics of the lower viscosity fluids resembles the rate-of-flow-controlled break-up, as reported earlier for the formation of bubbles in flow-focusing geometries [Garstecki P, Stone HA, Whitesides GM (2005) Phys Rev Lett 94:164501]. The results of this study can be helpful for a rationalized selection of liquids for the controlled formation of droplets with a predetermined size and with a narrow distribution of sizes.

The main challenge of mixing in microfluidic devices is that it is diffusion limited requiring meter long
channels for their completion. It was recognized that for faster mixing, additional local force that cause
transverse flow is required; for this purpose, passive mixers use obstacles and baffles and active mixers
supply external energy. This study concerns passive micro-mixing. In the past, improvement in mixing
efficiency has been sought through serpentine channels, very many obstacle arrangements, and a series
of baffles. The drawback of such complicated arrangements is that they are difficult to fabricate and if
implemented the pressure drop could be significant enough to cause stagnation. This led to our
hypothesis ‘Is it possible to design a single obstacle whose mixing efficiency is comparable to that due
to a collection of obstacles?’ We performed two dimensional numerical simulation of mixing flow in
a Y-microchannel with a single cylindrical obstacle and for various other configurations of multiple
cylindrical obstacles (linear, triangle, reverse triangle, square, rhombus, staggered asymmetric) as a
function of Reynolds number ranging between (1 - 300). We found that the mixing index (MI)
(efficiency) for a single cylindrical obstacle (70%) is nearly twice that of a square configuration (36%);
MI for a staggered arrangement of four cylindrical obstacles about the axis of the channel is even
higher (81%). Plots of local spatial variation of pressure and velocity, confirm the well-known role of
induced transverse pressure gradient in the wake of the obstacle causing transverse flows, and vortex
shedding, in mixing; Furthermore, we propose that a staggered arrangement of isobaric loops in the
region between the obstacle and the outlet, acts as virtual obstacles to aid mixing. Based on the above
inferences, we designed a new obstacle shaped like a tear-drop, such that the flow separates smoothly
at its leading edge to form vortices that can be made to act coherently to enhance mixing. We identified
two parameters to tune the mixing, viz, cone angle of the tear-drop and the axis angle with respect to
the flow axis: We found that a tear-drop with a cone angle of 750
and an axis angle of 600
displayed a
mixing index of 87%. To verify our proposal of staggered arrangement of isobaric loops causing
transverse flow we performed numerical simulation on a staggered arrangement of two perpendicular
baffles in a Y-channel by varying the inter-baffle distance. The results show that transverse flow
obtained through isobaric loops between the baffles are effectively used when greater spacing is
available between the second baffle and the outlet, as it allows the contour length of the interface
between the liquids to be stretched. We devised a new experimental protocol to measure the mixing
index to an accuracy of ±5% which included image processing routines; for a select configuration of
tear-drop and reverse triangle obstacle, experimentally obtained MI agrees with values from numerical
simulation. In the end, we report briefly our attempts to develop a passive electro-hydrodynamic mixer.

Integration and miniaturisation in electronics has undoubtedly revolutionised the modern world. In biotechnology, emerging lab-on-a-chip (LOC) methodologies promise all-integrated laboratory processes, to perform complete biochemical or medical synthesis and analysis encapsulated on small microchips. The integration of electrical, optical and physical sensors, and control devices, with fluid handling, is creating a new class of functional chip-based systems. Scaled down onto a chip, reagent and sample consumption is reduced, point-of-care or in-the-field usage is enabled through portability, costs are reduced, automation increases the ease of use, and favourable scaling laws can be exploited, such as improved fluid control. The capacity to manipulate single cells on-chip has applications across the life sciences, in biotechnology, pharmacology, medical diagnostics and drug discovery. This thesis explores multiple applications of optical manipulation within microfluidic chips. Used in combination with microfluidic systems, optics adds powerful functionalities to emerging LOC technologies. These include particle management such as immobilising, sorting, concentrating, and transportation of cell-sized objects, along with sensing, spectroscopic interrogation, and cell treatment. The work in this thesis brings several key applications of optical techniques for manipulating and porating cell-sized microscopic particles to within microfluidic chips. The fields of optical trapping, optical tweezers and optical sorting are reviewed in the context of lab-on-a-chip application, and the physics of the laminar fluid flow exhibited at this size scale is detailed. Microfluidic chip fabrication methods are presented, including a robust method for the introduction of optical fibres for laser beam delivery, which is demonstrated in a dual-beam optical trap chip and in optical chromatography using photonic crystal fibre. The use of a total internal reflection microscope objective lens is utilised in a novel demonstration of propelling particles within fluid flow. The size and refractive index dependency is modelled and experimentally characterised, before presenting continuous passive optical sorting of microparticles based on these intrinsic optical properties, in a microfluidic chip. Finally, a microfluidic system is utilised in the delivery of mammalian cells to a focused femtosecond laser beam for continuous, high throughput photoporation. The optical injection efficiency of inserting a fluorescent dye is determined and the cell viability is evaluated. This could form the basis for ultra-high throughput, efficient transfection of cells, with the advantages of single cell treatment and unrivalled viability using this optical technique.

In this paper, we present a new design of hollow, out-of-plane polymeric microneedle with cylindrical side-open holes for transdermal drug delivery (TDD) applications. A detailed literature review of existing designs and analysis work on microneedles is first presented to provide a comprehensive reference for researchers working on design and development of micro-electromechanical system (MEMS)-based microneedles and a source for those outside the field who wish to select the best available microneedle design for a specific drug delivery or biomedical application. Then, the performance of the proposed new design of microneedles is numerically characterized in terms of microneedle strength and flow rate at applied inlet pressures. All the previous designs of hollow microneedles have side-open holes in the lumen section with no integrated reservoir on the same chip. We have proposed a new design with side-open holes in the conical section to ensure drug delivery on skin insertion. Furthermore, the present design has an integrated drug reservoir on the back side of the microneedles. Since MEMS-based, hollow, side-open polymeric microneedles with integrated reservoir is a new research area, there is a notable lack of applicable mathematical models to analytically predict structural and fluid flow under various boundary conditions. That is why, finite element (FE) and computational fluid dynamic (CFD) analysis using ANSYS rather than analytical systems has been used to facilitate design optimization before fabrication. The analysis has involved simulation of structural and CFD analysis on three-dimensional model of microneedle array. The effect of axial and transverse loading on the microneedle during skin insertion is investigated in the stress analysis. The analysis predicts that the resultant stresses due to applied bending and axial loads are in the safe range below the yield strength of the material for the proposed design of the microneedles. In CFD analysis, fluid flow rate and pressure drop in the microneedles at applied inlet pressures are numerically and theoretically investigated. The CFD analysis predicts uniform flow through the microneedle array for each microneedle. Theoretical and numerical results for the flow rate and pressure drop are in close agreement with each other, thereby validating the CFD analysis. For the proposed design of microneedles, feasible fabrication techniques such as micro-hot embossing and ultraviolet excimer laser methods are proposed. The results of the present theoretical study provide valuable benchmark and prediction data to fabricate optimized designs of the polymeric, hollow microneedles, which can be successfully integrated with other microfluidic devices for TDD applications.

The interaction between ac electric fields and the induced charge in the double layer formed on top of electrodes generates steady motion of aqueous solutions. This phenomenon is termed ac electro-osmosis. Unidirectional fluid motion is obtained when the electrolyte is placed on top of an array of microelectrodes subjected to a travelling-wave potential. In this work, we analyse the generated fluid motion assuming that the electrodes are perfectly polarisable and making use of the nonlinear Gouy–Chapman model for the diffuse double layer. We approximate the applied potential at the level of the electrodes by a single-mode travelling wave. We present numerical and analytical solutions obtained in the weakly nonlinear regime and the results are discussed and related with previous experimental observations.

Spontaneous capillary flow (SCF) is a powerful method for moving fluids at the microscale. In modern biotechnology, composite channels-sometimes open-are increasingly used. The ability to predict the occurrence of a SCF is a necessity. In this work, using the Gibbs free energy, we derive a general condition for the establishment of SCF in any composite microchannel of constant cross section, i.e., a microchannel comprising different wall materials and even open parts. It is shown that SCF occurs when the Cassie angle is smaller than p/2 (h* \ p/2). For a homogeneous confined channel, this relation collapses to the well-known hydrophilic contact angle h \ p/2.

Molecular dynamics (MD) simulation is a powerful tool to investigate the nanoscale fluid flow. In this article, we review the methods and the applications of MD simulation in liquid flows in nanochannels. For pressuredriven flows, we focus on the fundamental research and the rationality of the model hypotheses. For electrokineticdriven flows and the thermal-driven flows, we concentrate on the principle of generating liquid motion. The slip boundary condition is one of the marked differences between the macro-and micro-scale flows and the nanoscale flows. In this article, we review the parameters controlling the degree of boundary slip and the new findings. MD simulation is based on the Newton's second law to simulate the particles' interactions and consists of several important processing methods, such as the thermal wall model, the cut-off radius, and the initial condition. Therefore, we also reviewed the recent improvement in these key methods to make the MD simulation more rational and efficient. Finally, we summarized the important discoveries in this research field and proposed some worthwhile future research directions.

Gas transport in micropores/nanopores deviates from classical continuum calculations due to nonequilibrium in gas dynamics. In such a case, transport can be classified by the Knudsen number (Kn) as the ratio of gas mean free path and characteristic flow diameter. The wellknown Klinkenberg correction and its successors estimate deviation from existing permeability values as a function of Kn through a vast number of modeling attempts. However, the nonequilibrium in a porous system cannot be simply modeled using the classical definition of the Kn number calculated from Darcy’s definition of the pore size or hydraulic diameter. Instead, a proper flow dimension should consider pore connectivity in order to characterize the rarefaction level. This study performs a wide range of pore-level analysis of gas dynamics with different porosities, pore sizes, and pore throat sizes at different Kn values in the slip flow regime. First, intrinsic permeability values were calculated without any rarefaction effect and an extended Kozeny-Carman model was developed by formulating the Kozeny-Carman constant by porosity and pore to throat size ratio. Permeability increased by increasing the porosity and decreasing the pore to throat size ratio. Next, velocity slip was applied on pore surfaces to calculate apparent permeability values. Permeability increased by increasing Kn at different rates depending on the pore parameters. While the characterization by the Kn value calculated with pore height or hydraulic diameter did not display unified behavior, relating permeability values with the Kn number calculated from the equivalent height definition created a general characterization based on the porosity independent from the pore to throat size ratio. Next, we extended the Klinkenberg equation by calculating unknown Klinkenberg coefficients which were found as a simple first order function of porosity regardless of the corresponding pore connectivity. The extended model as a combination of Kozeny-Carman for intrinsic permeability and Klinkenberg for apparent permeability correction yielded successful results.

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.

An acoustically activated micropump is fabricated and demonstrated using a single step lithography process and an off-chip acoustic energy source. Using angled lateral cavities with trapped air bubbles, acoustic energy is used to oscillate the liquid-air interface to create a fluidic driving force. The angled lateral cavity design allows for fluid rectification from the first-order pulsatile flow of the oscillating bubbles. The fluid rectification is achieved through the asymmetrical flow produced by the oscillating interface generating fluid flow away from the lateral cavity interface. Simulation and experimental results are used to develop a pumping mechanism that is capable of driving fluid at pressures of 350 Pa. This pumping system is then integrated into a stand-alone battery operated system to drive fluid from one chip to another.

This paper presents the first downscaling of electro membrane extraction (EME) to a chip format. The voltage-controlled extraction for sample preparation on microfluidic devices has several advantages such as selective extraction removing the high ionic strength of biological samples, preconcentration, fast kinetics with exact control of the beginning, and termination of the extraction. The device comprises a 25 lm thick porous polypropylene membrane bonded in-between two polymethyl methacrylate (PMMA) substrates with channel structures toward the membrane. The supported liquid membrane (SLM) was created by locally filling the pores of the membrane with 2-nitrophenyl octyl ether (NPOE). The sample solution, containing five basic model analytes in 10 mM HCl or urine was pumped through the 50 lm deep donor channel on one side of the membrane. With 15 V applied across the membrane, the protonated basic drugs were selectively extracted from the flowing sample solution, into the organic phase SLM, and further into just 7 ll of 10 mM HCl, serving as acceptor solution. Subsequently, the acceptor solution was analyzed by capillary electrophoresis. The electro membrane chip was highly efficient and even with flow rates resulting in the sample being in contact with the SLM for less than 4 s (3 ll min -1 ), 20-60% of the amount of the respective drugs in the sample was extracted. The large span in recovery was dependent on the physical properties of the drug substances compared to the SLM, and the individual drug substances were extracted with a RSD in the recovery of less than 5%.

Applicability of two kinds of computational-fluid-dynamics method adopting Cahn-Hilliard (CH) and Allen-Cahn (AC)-type diffuse-interface advection equations based on a phase-field model (PFM) is examined to simulation of motions of microscopic incompressible two-phase fluid on solid surface. A capillarity-driven gas-liquid motion in rectangular channel is simulated by use of a PFM method for solving Navier-Stokes (NS) equations and a CH equation, whereas an immiscible liquid-liquid flow in a microchannel with T-junction and square cross section is simulated by use of another PFM method proposed in this study, which adopts a lattice-Boltzmann method based on fictitious particles kinematics as numerical scheme for solving NS equations and an AC equation that is modified to improve volume-of-fluid conservation. The major findings are as follows: (1) effect of capillary force on the dynamic two-phase fluid system with a high density ratio is well predicted for cross-sectional aspect ratio of the channel = 1 and 2; (2) mono-dispersed slug flow pattern transition is reproduced in good agreement with experimental observations in terms of variation in length and interval of droplets as increasing their volumetric flow rates at a constant flow rate ratio = 1. These results prove that the PFM methods can be used for analyzing two-phase fluid motions in various microfluidic devices and micro fabrication processes.

We demonstrate a microfluidic continuous-flow protein separation process in which silica-coated superparamagnetic nanoparticles interact preferentially with hemoglobin in a mixture with bovine serum albumin, and the resulting hemoglobin-nanoparticle aggregates are recovered online using magnetophoresis. We present detailed modeling and analysis of this process yielding quantitative estimates of the recovery of both proteins, validated by experiments. While several previous studies utilize an average particle size in modeling magnetophoretic particle trajectories or process design, in this study we emphasize the importance of accounting for particle size distributions in calculating particle recovery, and therefore in estimating separation efficiency. We combine experimentally measured size distributions of protein-nanoparticle aggregates with simulations of particle trajectories and provide a simple analytical method to calculate the efficiency of separation at various flow speeds, which fully accounts for heterogeneity in particle sizes. Our method can potentially be used for affinity based biomolecular separations at both analytical and preparative scales by exploiting well-established techniques to functionalize nanoparticle surfaces with selective ligands. Further, the modeling methodology presented here may be applied to provide better estimates of particle recovery in a broad range of magnetophoretic separation processes involving heterogeneity in particle sizes.

This article presents the mixing performance of bio-mimetic cilia in a circular microchamber that is compatible with microwell plates. The mixing performance is characterized and compared with those of both diffusionand vibration-induced mixers. To represent the mixing performance, the 90% mixing time, which was the time span for 90% mixing completion, was measured by analyzing the mixing process of black ink with water. The cilia mixer reduced the 90% mixing time by 8.0-and 1.4 times compared with those of the diffusion-and vibration mixers, respectively. In addition, the coefficient of variation of the 90% mixing time for the cilia mixer was reduced by 3.1and 2.8 times compared with those of the diffusion-and vibration mixers, respectively. The experimental mixing performance was validated by numerical analysis. The simulations showed that the cilia mixer could significantly reduce the coefficient of variation because the convective flows generated by the cilia rapidly increased the surface area of the ink and thus rapidly decreased the variations in the initial mixing conditions.

A B S T R A C T Soft assemblies obtained following the Layer-by-Layer (LbL) approach are accounted among the most interesting systems for designing biomaterials and drug delivery platforms. This is due to the extraordinary versatility and flexibility offered by the LbL method, allowing for the fabrication of supramolecular multifunctional materials using a wide range of building blocks through different types of interactions (electrostatic, hydrogen bonds, acid-base or coordination interactions, or even covalent bonds). This provides the bases for the building of materials with different sizes, shapes, compositions and morphologies, gathering important possibilities for tuning and controlling the physico-chemical properties of the assembled materials with precision in the nanometer scale, and consequently creating important perspective for the application of these multifunctional materials as cargo systems in many areas of technological interest. This review studies different physico – chemical aspects associated with the assembly of supramolecular materials by the LbL method, paying special attention to the description of these aspects playing a central role in the application of these materials as cargo platforms for encapsulation and release of active compounds.

Biosensors based on nanotechnology are rapidly developing and are becoming widespread in the biomedical field and analytical chemistry. For these nanobiosensors to reach their potential, they must be integrated with appropriate packaging techniques, which are usually based on nano/microfluidics. In this review we provide a summary of the latest developments in nanobiosensors with a focus on label-based (fluorescence and nanoparticle) and label-free methods (surface plasmon resonance, micro/nanocantilever, nanowires, and nanopores). An overview on how these sensors interface with nano/microfluidics is then presented and the latest papers in the area summarized.

The literature includes a variety of analytical and semi-analytical models to describe squeeze-film damping in MEMS perforated structures. Even if many of them have been validated by means of numerical simulations, nobody seems to have discussed about the accuracy of numerical approaches in this field. In the present paper, we apply both the main analytical models and a commercial finite element software, COMSOL Multiphysics, to solve a good number of squeeze-film problems. They refer to some cases, which were experimentally investigated during the past by different authors. The tested structures are rigid rectangular plates fabricated with different material, different perforation ratio (i.e., the ratio of the hole side to the holes pitch) and different number of perforations. We compare both the analytical and the numerical results with the available experimental data, in order to have an overview about their effectiveness. Numerical simulations offer in all the considered cases valuable agreement with experiments.

A solvent vapor treatment was applied to femtosecond-laser-ablated microchannels in PMMA to selectively restore the original hydrophilic wetting behavior of the pristine surface. The hydrophobic surface of the microchannels from the submicron porosity induced by ablation becomes smoother and more transparent after the treatment. This simple and low-cost method, together with suitable masking, can produce wettability patterns that may be exploited to develop passive microfluidic elements such as valves and mixers.

In this contribution, a versatile, inexpensive and compact paper-based microfluidic biosensor was developed to detect heavy metals in food products. The underlying principle was based on sensing of ammonia (NH3) released during ureasecatalyzed hydrolysis of urea. At the presence of heavy metals, the amount of NH3 produced diminished due to inhibition of urease enzyme. Therefore, the concentration of target heavy metals could be indirectly determined from NH3, qualitatively, semi-quantitatively or quantitatively. Hydrophobic barriers of functional areas the sensor were fabricated by paraffin-dipping method. Urease enzyme was physically immobilized onto the sensor and phenol red was used for qualitative and semi-quantitative detection of heavy metal via image analysis. The sensor was also integrated into an electrochemical system using simple screenprinted electrodes. In the current study, Cu ++ was used as a model heavy metal for testing performance of the sensor. Qualitative results showed that a strong contrast between safe and unsafe sample, which was critical for the practical applicability of the sensor. Relationship between color intensity and Cu ++ concentration was characterized by a R 2 of 0.98 and the linear range covered Cu ++ concentrations from 0.01 -1 ppm. Detection limit was estimated to be 0.018 ppm which was well below standard limit established by WHO and EC for Cu ++ .

In this experimental study, the effects on twophase flow dynamics in a microfluidic snake channel due to periodic forcing were considered. Time series analysis was exploited to investigate on the obtained bubbles' flow considering two aspects: the role of driven frequency through Fourier analysis and the nonlinear behavior through the evaluation of d-infinite and Largest Lyapunov exponent. Phase diagrams summarize the results: the two nonlinear parameters are plotted versus the air fraction and the frequency of the input flow rates. The identified relation maps allow the classification of the flow dynamics, opening the way for the control of bubble flow through signal analysis.

Electroporation or electropermeabilization is one of the most powerful biological techniques in cell studies. Applying the high voltage electric field in vicinity of the cells can generate nanopores in cell membrane. Varying with the intensity and the duration of these applied electric field, the created nanopores can be temporary (reversible electroporation) or permanent (irreversible electroporation). Reversible electroporation is usually conducted to insert biological samples into the cells. Cells are also electroporated irreversibly to release their intercellular contents for further biological investigations. In comparison with the conventional electroporation devices, microfluidic (microscale) electroporation devices have some advantages such as higher cell viability rate, high transfection efficiency, lower sample contamination, and smaller Joule heating effect. In this article, the latest advancement in microfluidic cell electroporation is reviewed. First, the underlying theory of membrane permeabilization is reviewed and the leading analytical studies on the cell electroporation are presented. Following that, different experimental methods are compared. Finally, some suggestions are proposed for the future studies.

Due to the low Reynolds number associated with microscale fluid flow, it is difficult to rapidly and homogenously mix two fluids. In this letter, we report a fast and homogenized mixing device through the use of a bubble-based microfluidic structure. This micromixing device worked by trapping air bubbles within the predesigned grooves on the sidewalls of the channel. When acoustically driven, the membranes (liquid/air interfaces) of these trapped bubbles started to oscillate. The bubble oscillation resulted in a microstreaming phenomenonstrong pressure and velocity fluctuations in the bulk liquid, thus giving rise to fast and homogenized mixing of two side-by-side flowing fluids. The performance of the mixer was characterized by mixing deionized water and ink at different flow rates. The mixing time was measured to be as small as 120 ms.

In this paper we present electro-osmotic (EO) flow within a more traditional fluid mechanics framework. Specifically, the modified Bernoulli equation (viz. the energy equation, the mechanical energy equation, the pipe flow equation, etc.) is shown to be applicable to EO flows if an electrical potential energy term is also included. The form of the loss term in the modified Bernoulli equation is unaffected by the presence of an electric field; i.e., the loss term still represents the effect of wall shear stress, which can be represented via a friction factor. We show that that the friction factor for pure EO flow (no applied pressure gradient) varies inversely with the Reynolds number based on the Debeye length of the electric double layer. Expressions for friction factor for combined laminar pressure-driven and EO flow are also given. These are shown to be functions of Reynolds number and geometry, as well as the relative strength of the applied electric field to the applied pressure gradient.

The investigation of human disease mechanisms is difficult due to the heterogeneity in gene expression and the physiological state of cells in a given population. In comparison to bulk cell measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. In this review, we describe the recent advances in single-cell technologies and their applications in single-cell manipulation, diagnosis, and therapeutics development.

Electrosprays routinely create sub-micron droplets containing functional molecules and show promise as a drop-on-demand dispensing method in the life sciences and materials processing. To precisely eject minute liquid volumes electrosprays must be turned on for milliseconds or less in the cone-jet or high-frequency pulsation mode. This work reports sequential phenomena which occur when electrosprays are triggered by sudden voltage steps. For low voltages the electrospray enters the pulsation mode but the pulsation frequency increases towards an asymptote, which increases with voltage. For higher voltages the asymptotic frequency is above a critical value and the electrospray switches to the cone-jet mode; after this the ejection rate increases until finally reaching a steady state. The total delay involves these phenomena plus the delay in forming a liquid cone; the latter depends strongly on both the initial and final voltage. The final electric field that must be applied is smaller when the electric field the liquid is subjected to initially is small-it is proposed that the inertia of a dynamically forming cone plays a role in lowering the voltage needed.

The aim of this work is to study the pore blocking by the use of microfluidic devices (microseparators) and numerical simulation approaches. The microseparators are made in PDMS and are constituted of an array of microchannels 20 lm wide with three types of structure: straight microchannels, connected microchannels (or aligned square pillars) and staggered square pillars in order to mimic merely the complexity of the flow encountered in filters or membranes (tortuosity, connectivity between pores). Direct observation with video microscopy of filtrations of 5 lm latex particles has been performed to examine the capture of particles. The results show a piling up of particles within the porous media leading to a clogging. The capture efficiency remains low (\0.1 %). In the case of filtration in the forest of pillars, the capture is faster and arises mainly between the pillars. The increase in tortuosity in the microseparator leads then to a rise of the clogging. It must be caused by the increase in critical trajectories leading to the capture of particles on the PDMS walls. At the same time, numerical simulations of filtration in parallel with microchannels have been performed in the same flow conditions with GeoDict software. The different kind of experimental deposit structure can be simulated, but there is still inaccuracy in the description of the accumulation kinetics. These discrepancies are probably due to the lack of accuracy to depict particle/particle colloidal interactions in simulations and the fact that re-suspension of particles after capture is not well described.

The present work aims at studying the nonlinear breakup mechanism for Taylor bubble formation in a microfluidic flow-focusing device by using a high-speed digital camera. Experiments were carried out in a square microchannel with cross section of 600 9 600 lm. During the nonlinear collapse process, the variation of the minimum radius of bubble neck (r 0) with the remaining time until pinch-off (s) can be scaled by a power-law relationship: r 0 / s a : Due to the interface rearrangement around the neck, the nonlinear collapse process can be divided into two distinct stages: liquid squeezing collapse stage and free pinch-off stage. In the liquid squeezing collapse stage, the neck collapses under the constriction of the liquid flow and the exponent a approaches to 0.33 with the increase in the liquid flow rate Q l. In the free pinch-off stage, the value of a is close to the theoretical value of 0.50 derived from the Rayleigh-Plesset equation and is independent of Q l .