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Inertial focusing microfluidics have gained significant momentum in the last decade for their ability to separate and filter mixtures of particles and cells based on size [1-3]. However, the most important feature is that the separation is passive, without the need for external forces. At the heart of inertial focusing is the balance between counteracting lift forces: shear and wallinduced lift. Shear-induced lift is a product of the curvature of the fluid flow and the rotation of the particle in the flow, while wall-induced lift is generated by the disturbance of the fluid by the particle near a wall. This phenomenon was first observed by Segre and Silberberg for the focusing of particles in a pipe, and was later extended to the focusing of cells and particle in rectangular channels [4]. Taking advantage of inertial focusing we explore particle capture utilizing an expanded channel microfluidics chip design. By expanding a small region of the straight channel microvortices form in the well, which allows for size selective trapping of particles.

Obstructions in airways result in significant alterations in ventilation distribution and consequently reduce the ventilation to perfusion ratio, affecting gas exchange. This study presents a lumped parameter-based model to quantify the spatial ventilation distribution using constructal theory. An extension of the existing theory is made for the conductive bronchial tree and is represented in matrix frame incorporated with airway admittances. The proposed lung admittance model has a greater advantage over the existing methodologies based on lung impedance, as it can be applicable for both fully and partially blocked regions. We proved the well-posedness of the problem, and the generated matrix is highly sparse in nature. A modified block decomposition method is implemented for symmetric and asymmetric trees of various obstructions [Formula: see text] to reduce the memory size. The asymmetry is considered in every left branch of the bronchial tree recursively, following the mathematical relations: [Formula: see text] and [Formula: see text], where L and D are the length, diameter of the jth branch at ith generation, respectively, for [Formula: see text]. It is observed that relative flow rate [Formula: see text] decreases exponentially with the generation index. In tidal breathing, the regional ventilation pattern is found to vary spatially instead of spatio-temporally. The comparison of our result with the clinical data is found to be accurate when 40% or more obstruction is considered in the proximal region (observed in asthma). Moreover, this predicts an increment of lung impedance by 6%, which can be used for further improvement of clinical observations.

Non-contact manipulation methods capable of trapping and transporting swimming bacteria can significantly aid in chemotaxis studies. However, high swimming speed makes the trapping of these organisms an inherently challenging task. We demonstrate that an optoelectric technique, rapid electrokinetic patterning (REP), can effectively trap and manipulate Enterobacter aerogenes bacteria swimming at velocities greater than 20 μm s(-1). REP uses electro-orientation, laser-induced AC electrothermal flow, and particle-electrode interactions for capturing these cells. In contrast to trapping non-swimming bacteria and inert microspheres, we observe that electro-orientation is critical to the trapping of the swimming cells, since unaligned bacteria can swim faster than the radially inward electrothermal flow and escape the trap. By assessing the cell membrane integrity, we study the effect of REP trapping conditions, including optical radiation, laser-induced heating, and the electric field on cell viability. When applied individually, the optical radiation and laser-induced heating have negligible effect on cells. At the standard REP trapping conditions fewer than 2% of cells have a compromised membrane after four minutes. To our knowledge this is the first study detailing the effect of REP trapping on cell viability. The presented results provide a clear guideline on selecting suitable REP parameters for trapping living bacteria.

The flow enhancement and convective heat transfer along with entropy generation analysis are studied numerically in a micro-slit with alternating hydrodynamic slip patches. The advances in molecular simulations and micro-scale experiments confirmed that the slip of fluid on the solid surfaces occurred at small scale flows and the traditional no-slip boundary conditions cannot be applicable for the flow simulation at the micro- and nano-scale. The coupled Poisson–Boltzmann–Navier–Stokes equations dealing with an external electric potential are involved for the flow enhancement and entropy generation analysis of non-Newtonian fluids in a micro-slit with periodic slips. From the finite volume simulation, it is observed that the drag force effect is very strong along the wall for the transportation and mixing of fluids. This effect is found to be minimized by imposing periodic hydrophobic slippage along the boundary. An additional pressure gradient is generated by imposing electrokinetic pumping, resulting in a higher velocity gradient in the flow direction in the presence of viscous dissipation and Joule heating effects. The results are predicted in terms of the flow enhancement factor (Ef) (which provides maximum species transport), the average heat transfer rate (Nu), and the average entropy generation due to fluid friction, heat transfer, and Joule heating effects. The advantages and disadvantages of utilizing slip conditions are discussed, which has large scale applications on drug delivery and DNA analysis and sequencing, since cell damage due to pumping will be minimized.

Rapid electrokinetic patterning (REP) is an emerging optoelectric technique that takes advantage of laser-induced AC electrothermal flow and particle-electrode interactions to trap and translate particles. The electrothermal flow in REP is driven by the temperature rise induced by the laser absorption in the thin electrode layer. In previous REP applications 350-700 nm indium tin oxide (ITO) layers have been used as electrodes. In this study, we show that ITO is an inefficient electrode choice as more than 92% of the irradiated laser on the ITO electrodes is transmitted without absorption. Using theoretical, computational, and experimental approaches, we demonstrate that for a given laser power the temperature rise is controlled by both the electrode material and its thickness. A 25-nm thick Ti electrode creates an electrothermal flow of the same speed as a 700-nm thick ITO electrode while requiring only 14% of the laser power used by ITO. These results represent an important step in the design of low-cost portable REP systems by lowering the material cost and power consumption of the system.

Droplet microfluidics is enabling reactions at nano- and picoliter scale, resulting in faster and cheaper biological and chemical analyses. However, varying concentrations of samples on a drop-to-drop basis is still a challenging task in droplet microfluidics, primarily limited due to lack of control over individual droplets. In this paper, we report an on-chip microfluidic droplet dilution strategy using three-valve peristaltic pumps.

In this work, we discuss an optical method for measuring surface tension induced menisci. The principle of measurement is based upon the change in the background pattern produced by the curvature of the meniscus acting as a lens. We measure the meniscus profile over an inclined glass plate and utilize the measured meniscus for estimation of surface tension and refractive index.

Droplet microfluidics offers an effective way for compartmentalizing samples and reagents for various biological and/or biochemical assays. However, an active control over size and frequency of individual droplets is quite difficult to achieve with off-chip pumping mechanisms such as syringe pumps. In this article, we propose the use of programmable microfluidic architectural components for spatiotemporal droplet control. On-chip three-valve diaphragm pumps were used to drive both dispersed and carrier phases toward a microfluidic T-junction. Individual droplet sizes and spacings were varied by controlling the number of pump cycles for injection and break-off. Droplet generation frequency was modulated by adjusting valve actuation rate. Droplet sizes were quantified for various pump parameters to identify the parametric space for stable and reliable droplet generation. Complex droplet trains with variable drop sizes and spacing were created by programming the desired pump states. Combinatorial merging and mixing of two droplets in various volumetric ratios was performed in a divergent mixing geometry to demonstrate utility of this technology.

A simple optical setup is introduced here that is capable of improving the diffraction-limited angular resolution of a telescope at minimal cost to image quality. The system consists of, at minimum, an axicon and a convex lens located in the optical path of the telescope, which can increase the angular resolution by up to 38%. Analytical results for this resolution gain along with the Strehl ratio of this system are presented along with experimental results, which show a 30% improvement in single-acquisition image resolution with a Strehl ratio of 0.07, agreeing well with predicted values. With an ultrashallow axicon, large increases in Strehl ratio are possible, up to and beyond unity making higher angular resolution measurements possible with little cost to image quality or experimental complexity.

For the last 50 years the state-of-the-art for studying electrophysiological activity of single cells has been based on an investigator using a single microprobe, and attempting to make relevant recordings, one cell at a time. Here we report the design, fabrication and characterization of a MEMS-based lab-on-a-chip system for measuring Ca 2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real-time multidimensional calcium flux patterns around 16 Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The 16 microfluidic cell holding pores are 150 μm × 150 μm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The in silico cell physiology lab is wire bonded onto a custom PCB for easy interface with a state-of-the-art data acquisition system. The electrodes are coated with a Ca 2+ ion-selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Characterization results have shown Nernst slopes of 30 mV/decade that were stable over a number of measurement cycles, and actual fern spore Ca 2+ measurements have been recorded with high repeatability and reproducibility. While this work is focused on technology to enable basic research on C. richardii spores, we anticipate that this type of cell electrophysiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique.

Rapid electrokinetic patterning (REP) is an emerging optoelectric technique that takes advantage of laser-induced AC electrothermal flow and particle-electrode interactions to trap and translate particles. The electrothermal flow in REP is driven by the temperature rise induced by the laser absorption in the thin electrode layer. In previous REP applications 350-700 nm indium tin oxide (ITO) layers have been used as electrodes. In this study, we show that ITO is an inefficient electrode choice as more than 92% of the irradiated laser on the ITO electrodes is transmitted without absorption. Using theoretical, computational, and experimental approaches, we demonstrate that for a given laser power the temperature rise is controlled by both the electrode material and its thickness. A 25-nm thick Ti electrode creates an electrothermal flow of the same speed as a 700-nm thick ITO electrode while requiring only 14% of the laser power used by ITO. These results represent an important step in the design of low-cost portable REP systems by lowering the material cost and power consumption of the system.

Illumination patterns are used to drive electrothermal flows for sorting and manipulating particulates for Lab-on-Chip applications. Plasmonics has been used to enhance the optical coupling.

By harnessing the photo-induced heating of a single plasmonic nanostructure and AC E-field in our research at the interface between plasmonics and optofluidics we demonstrate on-demand fluid flow control with unparalleled micron per second-scale velocities.

In this paper, we report the design, fabrication and characterization of an In Silico cell physiology biochip for measuring Ca2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real time multidimensional calcium flux patterns around sixteen Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The sixteen microfluidic cell holding pores are 150 by 150 µm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The In Silico cell physiology lab is wire bonded on to a custom PCB for easy interface with a state of the art data acquisition system. The electrodes are coated with a Ca2+ ion selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Initial characterization results have shown Nernst slopes of 30mv/decade that were stable over a number of measurement cycles. While this work is focused on technology to enable basic research on the Ceratopteris richardii spores, we anticipate that this type of cell physiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique. Future applications include detection of glucose, hormones such as plant auxin, as well as multiple analyte detection on the same chip.

This paper presents analytical derivations of the pressure distribution in straight and uniform rectangular microchannels in the slip flow regime and new experimental data in those channels. The flow is to be steady state, two-dimensional, isothermal, and to have negligible transverse velocities with a first order slip boundary condition. The measured pressure distributions of airflows are compared with newly derived analytical results. There is close agreement between the measurements and calculation by the slip flow formula. The dimensionless location of the maximum deviation from the linear pressure distribution is found analytically and compared with the measurements. This dimensionless location of the maximum deviation increases with the increasing pressure ratios in the slip flow regime. The effect of several parameters such as the channel aspect ratio and the Knudsen number on the locations of maximum deviation from linearity are investigated. The nonlinearity of the pressure distribution is also discussed.

This paper describes the fabrication and characterization of a microelectronic device for the electrical interrogation and impedance spectroscopy of biological species. Key features of the device include an all top-side processing for the formation of fluidic channels, planar fluidic interface ports, integrated metal electrodes for impedance measurements, and a glass cover sealing the non-planar topography of the chip using spin-on-glass as an intermediate bonding layer. The total fluidic path volume in the device is on the order of 30 nl. Flow fields in the closed chip were mapped by particle image velocimetry. Electrical impedance measurements of suspensions of the live microorganism Listeria innocua injected into the chip demonstrate an easy method for detecting the viability of a few bacterial cells. By-products of the bacterial metabolism modify the ionic strength of a low conductivity suspension medium, significantly altering its electrical characteristics.

Here we present an optical measurement technique and image analysis process capable of tracking particles in three dimensions with a single point of view. In addition to single view 3D-PTV, the optical system is capable of tracking individual particles even at particle-particle spacings that are closer then the diffraction limit of the base imaging system. The measurement system, termed Bessel Beam Microscopy (BBM), functions as an attachment for a microscope that fits between the microscope base and camera. The addition of the BBM attachment transforms the point spread function (PSF) of the microscope allowing two unique functions: single image superresolution imaging, and the extraction of three dimension location information of particles without calibration. The result is a fluid characterization tool with unique capabilities for velocimetry and characterization of the dynamics of dense fluid-particle suspensions.

We have recently developed a novel colloidal particle manipulation technique that we call Rapid Electrokinetic Patterning (REP) capable of dynamically manipulating colloids as small as 50 nm. Article not available.

Due to the relevance of capillary flows for industrial applications, the dynamics of menisci have been extensively investigated. Contrary to the meniscus velocity, the flow pattern near the meniscus is rather unexplored. The main focus of this study is the visualization of the flow field near the fast moving meniscus with micro particle image velocimetry (μPIV). Therefore an invasive flow of ethanol in a vertical cylindrical glass tube is investigated. The entrance of the tube is located inside a reservoir with a rising liquid surface. Especially near the tube entrance the flow is high dynamical (ca. 120 mm/s) which necessitates high temporal resolution measurement techniques. Flow field measurements at several positions in flow direction have been conducted to compare the meniscus shape and the flow fields near the three phase contact line. The flow pattern near the meniscus is extremely complex. While the typical Hagen-Poiseuille profile with no radial velocity component is to be found far from the meniscus, the flow near the meniscus cannot be a convex velocity profile. As a matter of fact the meniscus movement is characterized by adsorption of the liquid near the wall and liquid transport from the middle of the flow to the three phase contact line. This special flow pattern has been examined. Furthermore it was found that the shape of the meniscus varies over the whole invasion of the tube. The curvature of the meniscus and therefore the contact angle between solid and liquid are getting smaller over the infiltration length which has influence on the capillary force. Measurements near the entrance of the tube show an acceleration of the liquid column until it reaches a certain speed and after that a deceleration. To determine the velocity of the raising meniscus, global measurements of the whole tube have been performed.Copyright © 2008 by ASME

In this paper we demonstrate opto-electrothermal pumping in a very simple setup consisting primarily of parallel electrodes and explore the characteristics of such flows with different optical intensity patterns. For our parallel electrode configuration setup, ITO-coated electrodes were used to generate electric fields. The optical illumination system uses a laser beam (continuous wave, 1,064 nm). The experiments are analyzed in terms of existing analytical models for electrothermal flows. Microvortices created using the electric field and focused laser beam resembles a sink/source type flow with the laser spot as the center of the sink/source. The flow velocity is characterized as a function of the AC signal frequency and the strength of electric field. At larger frequencies (f > 1 MHz), the velocity of the vortices decreases and around f > 5 MHz, Brownian motion dominates fluid flow. The line illumination is created by holographically stretching the point illumination. The line is about 28 μm in length. Result of this experiment is determined by means of visualization only. The creation of these vortices can not only be used to create microfluidic pumps but also also show immense promise as microfluidic mixers without utilizaing any invasive components.

Flow phenomena are of great importance in the study of biological systems: both natural organisms and biomedical devices. Although scientists and engineers have an excellent understanding of transport processes at large length scales, the study of transport processes at cellular length scales and smaller is just beginning. Considering the importance of biological activities at and below the cellular level (see also this volume, Part III, chapter 2.1, by Huang, Sultan, and Ingber), it is critical to understand the microfluidic environment in which these processes occur and how we can manipulate them. Recent strides in micrometer- and nanometer-scale diagnostic techniques have allowed exploration of flow phenomena at length scales comparable to single cells, and even smaller. One of the most useful means of manipulating fluids and suspended species such as cells, DNA, and viruses is with electric fields. Electrokinetic phenomena are important at micron length scales, and can be used to manipulate fluid and particle motion in microfluidic devices. This chapter will briefly review the various methods of electrokinetic fluid and particle manipulation, then review the recently developed microfluidic diagnostic processes available for assessing flow behavior at micron length scales, and finally discuss in detail advances in electrothermal and dielectrophoretic fluid and particle manipulation.

The current work deals with numerical simulation of optical trap systems at time scales varying from very small to very large. This analysis is important to understand the effects of different forces acting on the optically trapped particle. The significance of inertia forces are also evaluated at these time scales. A novel method of computing diffusion coefficient from the simulated values is proposed. It has been shown that the computed values of the diffusion coefficient are an exact match to the theoretical results.Copyright © 2007 by ASME

Trans-cellular calcium currents play a central role in the establishment of polarity in differentiating cells. Typically these currents are measured and studied experimentally using ion selective glass microelectrodes. We have recently developed an in silico cell electrophysiology lab-on-a-chip device with the specific science objectives of measuring these transcellular calcium currents in an advanced throughput format. The device consists of 16 pyramidal pores on a silicon substrate with four Ag/AgCl electrodes leading into each pore on the four poles. An SU-8 layer is used as the structural and insulating layer and a calcium ion selective membrane is used to impart ion selectivity to the Ag/AgCl electrodes. In this paper we demonstrate the utility of the cell electrophysiology biochip in measuring these transcellular calcium currents from single cells using the model biological system Ceratopteris richardii. We monitored these fern spores during germination and pharmacologically inhibited biophysical calcium transport. These results demonstrate the utility and versatility of the in silico cell electrophysiology biochip. While this version of the biochip was engineered to fulfill the specific science objectives of measuring trans-cellular calcium currents from Ceratopteris fern spores, the chip can easily be modified for a variety of biomedical and pharmacological applications. Future

Biological agent detection has captured the attention of many researchers over the last few years. The present research explores the possibility of directly measuring the diffusion coefficients of sub-micron particles as a means of pathogen detection. At a constant temperature, the diffusion coefficient is simply a function of the drag on the particle. If the particles are functionalized with antibodies against a specific analyte and introduced into a sample containing that analyte, binding of the analyte with the particles will increase the particles' hydrodynamic drag. This results in a decrease in diffusion, which is measured by a particle tracking algorithm. The reduction in diffusion is correlated with the amount of analyte present. Sensitivity to experimental conditions is also explored and it is shown that alternate methods like optical traps provide an even better technique for biological agent detection.Copyright © 2006 by ASME

Experimental visualizations of the 3D convection patterns generated near an evaporating meniscus in a capillary tube are presented. Epi-fluorescent micro-particle image velocimetry (μPIV) using a two-cavity frequency doubled ND-YAG laser as the illumination source is employed to map the small-scale spatial flow fields near the meniscus. Methanol seeded with 0.5 μm polystyrene fluorescent particles is used as the experimental fluid. These fluorescent particles absorb light from the laser beam (λabs~542 nm, green) and emit a longer wavelength light ((λem~612 nm, red). Images obtained at a specified time delay (~20 ms) were interrogated to obtain vector flow fields.Copyright © 2006 by ASME

Recently a new μPIV interrogation algorithm has been proposed in which the interrogation window size is reduced to a single pixel. Such small interrogation window sizes are possible using correlation averaging to increase the effective particle concentration to levels required for correlation analysis to succeed. The random error exhibits the expected behavior of decreasing roughly in proportion to N−1/2 while the bias error exhibits unexpected peak-locking behavior with zero bias error at integer and half integer pixel displacements and maximal errors at one-quarter and three-quarter pixel displacements. Accompanying experiments show the potential of this technique but have not yet been sufficiently refined to confirm this unexpected bias error behavior.Copyright © 2005 by ASME

Mixing characteristics in a 2D serpentine micro-channel were studied experimentally to understand the role of Dean vortices in enhancing mixing. Mixing plane deformation was visualized at Reynolds numbers ranging from 1 to 200 with the corresponding Dean numbers ranging from 1 to 205. The 2D serpentine micro-channel was found to be a poor mixer for Re100. This study will have a significant impact on the understanding of transport properties of flows in similar geometries.

A rigid spherical particle translating at small tube Reynolds number in a shearing flow experiences lateral migration due to small inertia and wall effect. In a suspension flow of sufficiently small particles, Brownian motion is another factor. In this work, we investigate this migration phenomenon of Brownian particles in a pressure-driven flow for a range of particle volume fractions (φ) much less than 0.01. The flow velocity is varied, which results in bulk Peclet number (Pe) ranging over four orders of magnitude. Both the velocity and the particle distributions were measured. It has been found that when Pe is smaller than 1000, particles migrate away from the channel wall, and that the particle concentration in regions remote from the wall (more than 10 particle diameters) is nearly uniform; When Pe increases beyond 1000, particles move toward a preferred position with the migration effect becoming progressively stronger as Pe increases.Copyright © 2004 by ASME

Particle image velocimetry (PIV), a technique commonly used at macroscopic length scales to measure velocity fields of particle-seeded flows, is adapted to measure velocity fields in microfluidic MEMS devices, where micron-scale spatial resolution is critical. Adapting PIV to the microscopic level presents a number of challenges, including visualizing tracer particles that are smaller than the wavelength of light and minimizing errors due to the Brownian motion of the tracer particles. High numerical aperture video microscopy is used to record the faint signals from fluorescent 300 nm particles. Innovative ensemble averaging and adaptive spatial shifting algorithms are used to extract maximal information from the recorded images. The PIV technique is used to measure a low Reynolds number Hele-Shaw flow around an 8 μm human red blood cell. The velocity vector field presented has a maximal spatial resolution of 3.2 × 3.2 × 1.5 μm.

Self-assembly of micron sized and smaller particles has previously been demonstrated using biologically inspired events such as DNA hybridization and interactions of ligands and receptors. In order to implement these techniques to create practical electronic devices, a quantitative measure of the amount of substance attached to the device surface just prior to the final assembly is essential. In the present investigation, this crucial quantity was investigated from the electrophoretic mobility of particles, which was ascertained by examining their motion under applied electric fields ranging from 0 to 1 V/mm. Sequential CCD camera images processed with custom software enabled calculation of particle velocities during their viscous motion in an inexpensive electrophoresis chamber filled with a low-conductivity buffer solution. A linear fit through the velocity vs. electric field data points yielded the electrophoretic mobility, which was utilized in the Stokes equation to calculate the net amount of charge present on each device. For 5.44 micron carboxyl-coated polystyrene beads, this method indicated a charge of 2.69e-15 C per particle. The manufacturer of the beads, Spherotech corporation, quoted 6.37e-11 C as the expected charge. The more than three orders of magnitude discrepancy is at least partially attributable to the electrophoretic retardation and relaxation effects of small electrolyte ions in the buffer solution. The method was also applied to silicon islands in the shape of a cone frustum with similar dimensions to the beads. A mercapto-ethane-sulfonate monolayer, attached via thiol bonds to the gold-coated surface of the islands, provided the charge. The amount of charge on an island was calculated to average 2.48e-15 C, corresponding to a density of 3.82e10 mercapto-ethane-sulfonate groups per square centimeter of Au surface.

The photo-induced collective heating enabled by a plasmonic nanoantenna array is for the first time harnessed for rapid concentration, manipulation and sorting of particles, with high throughput. This work could find application in biosensing, and surface enhanced spectroscopies.