Microfluidics and Nanofluidics

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.

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.

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.

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.

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.

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.

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.

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.