Mohamed Abdelgawad

Droplet-Scale Estrogen Assays in Breast Tissue, Blood, and Serum

A digital electrode array, on which drops of solvent can be electronically manipulated, allows automated steroid extraction from tiny tissue samples for diagnosis or research. Extracting Estrogen from Small Samples Microfluidic devices, in which small samples are manipulated within narrow channels, have been profitably applied to clinical sample analysis and biomedical research. These devices have advantages over more standard analysis techniques because they require only limited amounts of reagents, a boon when reagents are expensive. In addition, microfluidic devices are easy to make and can handle multiple processes and multiple samples on a single platform, enabling automation and scale-up. In closely related digital microfluidic (DMF) devices, the usual channels through which liquids are pumped or electrically coaxed are replaced by arrays of flat electrodes. When an electrical potential is applied to an electrode, the surface becomes locally charged, such that the droplet moves to that region. When several electrodes are charged, one by one, droplets can be made to move across the surface (and dispense and mix) in a controlled fashion. To be moveable, liquids must be slightly conductive or have dipole moment > 1; fortunately, most liquids fall into this category. This DMF technology has now been harnessed by Mousa et al. for extraction of the steroid estradiol from very small tissue or blood samples for ultimate quantitation. Steroid hormones, which regulate essential reproductive and homeostatic functions in the human body, are routinely measured clinically in blood but not in tissue because of the large samples that would be required by current methods. Separation of steroids from other biological components is usually necessary for accurate measurements because these components often interfere with the assays. To enable measurement of estrogen in tissues or small samples of blood, Mousa et al. have used DMFs and built a device to extract estradiol from 1-μl samples. In their method, the biological sample is dried onto one of the electrodes and a lysing solvent is moved by application of electrical potential to the sample and dried. Then, a polar solvent moves to the sample, extracting soluble material, including steroids. The droplet containing the steroid (and other components) is then circulated within a pool of nonpolar solvent; many of the interfering compounds partition into the nonpolar liquid. The polar droplet, still containing the steroid, is moved out of the nonpolar solvent pool and dried on an electrode, ready for quantitation. For routine application, the extraction process will need to be linked to an automated measurement method. A convenient technique for measuring estrogen in small amounts of breast tissue or tumor, for example, would allow testing whether failure to respond to therapy with selective estrogen receptor modulators such as tamoxifen or aromatase inhibitors is a result of locally high estrogen concentrations in the tumor and whether breast cancer risk can be predicted by local estrogen concentrations. Further, androgen concentrations in the prostate could be measured to check their influences on cancer. Estrogen is a key hormone in human reproductive physiology, controlling ovulation and secondary sexual characteristics. In addition, it plays an important role in the pathogenesis of breast cancer. Indeed, estrogen receptor antagonists and aromatase inhibitors (which block estrogen biosynthesis) are primary drugs used for treatment and prevention in at-risk populations. Despite its importance, tissue concentrations of estrogen are not routinely measured because conventional techniques require large samples of biopsies for analysis. In response to this need, we have developed a digital microfluidic method and applied it to the extraction and quantification of estrogen in 1-microliter samples of breast tissue homogenate (as would be collected with fine-needle aspiration), as well as in whole blood and serum. This method may be broadly applicable to conditions requiring frequent analysis of hormones in clinical samples (for example, infertility and cancer).

MICROCHANNEL HEAT SINKS: AN OVERVIEW OF THE STATE-OF-THE-ART

Computers are rapidly becoming faster and more versatile, and as a result, high-powered integrated circuits have been produced in order to meet this need. However, these high-speed circuits are expected to generate heat fluxes that exceed the circuits allowable operating temperature, and so an innovative cooling device is needed to solve this problem. Microchannel heat sinks were introduced in the early 1980s to be used as a means of cooling integrated circuits. Since then, many studies have been conducted in the field of these microchannel heat sinks. Earlier research used mainly single-phase coolants in their heat sinks, but two-phase coolants are now the focus of more recent research. The purpose of this article is to present a state-of-the art literature review of the progress of research in the field of microchannel heat sinks. This literature will focus mainly on the most recent research, starting with the latter half of the 1990s.

Optimization of device geometry in single-plate digital microfluidics

Digital microfluidics is a popular tool for lab-on-a-chip applications and is typically implemented in one of two formats: single-plate (“open”) devices or two-plate (“closed”) devices. Single-plate devices have some advantages relative to the more common two-plate format such as faster mixing, the capacity to move larger volumes on a given footprint, and easier access to droplets for handling or optical detection. In contrast with the two-plate format, in which ground potential is generally supplied via a top electrode, in the single-plate format, many different geometries of ground wires/electrodes have been used. Until the present study, there has been no metric to determine which of these geometries is best suited for droplet actuation. Here, we present a combination of numerical simulations and experimental tests to compare six different single-plate designs. We applied finite element analysis, using the commercially available COMSOL software package to calculate the electrodynamic actuation forces i...

TRANSIENT BEHAVIOR OF THE VISCOUS MICROPUMP

In the present study, the transient performance of the viscous micropump will be investigated numerically. The viscous micropumps operation depends mainly on viscous forces and can operate in any situation where viscous forces are dominant. All the micropump calculations are reported in nondimensional quantities, which allows for the prediction of the micropump performance, regardless of the dimensions or the fluid that is used. The effect of the microchannel height, rotor eccentricity, Reynolds number, and pump load on the transient performance of the viscous micropump has been studied in detail. The steady state performance was compared with the available experimental data and was found to be in a very good agreement. The rotor eccentricity was determined to be the parameter that affected the transient performance of the micropump the most significantly. This work provides a foundation for future research on the subject of fluid phenomena in viscous micropumps.

Electrical power free, low dead volume, pressure-driven pumping for microfluidic applications.

This paper presents a simple-to-construct, low dead volume pump capable of generating a wide range of positive and negative pressures for microfluidic applications. The pump generates pressure or vacuum by changing the volume of air confined inside a syringe and is able to generate pressures between -95 and +300 kPa with a resolution as high as 1 Pa. Different from syringe pumps and electrokinetic pumping, which are capable of controlling flow rates only, our pump can be used to generate constant flow rates or constant pressures, which are required for certain applications such as the aspiration of biological cells for biophysical characterization. Compared to syringe pumps, the new pump has almost zero dead volume and does not exhibit pulsatile flows. Additionally, the system does not require electrical power and is cost effective (∼

Digital Microfluidic Processing of Mammalian Embryos for Vitrification

100). To demonstrate the capabilities of the pump, we used it to aspirate osteoblasts (MC3T3-E1 cells) and to determine Youngs modulus of the cells, to generate a concentration gradient, and to produce variable-sized droplets in microchannels using hydrodynamic focusing.

Numerical Investigation of Multistage Viscous Micropump Configurations

Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

Repulsion-based model for contact angle saturation in electrowetting

The viscous micropump consists of a cylinder placed eccentrically inside a microchannel, where the rotor axis is perpendicular to the channel axis. When the cylinder rotates, a net force is transferred to the fluid because of the unequal shear stresses on the upper and lower surfaces of the rotor. Consequently, this causes the surrounding fluid in the channel to displace toward the microchannel outlet. The simplicity of the viscous micropump renders it ideal for micropumping; however, previous studies have shown that its performance is still less than what is required for various applications. The performance of the viscous micropump, in terms of flow rate and pressure capabilities, may be enhanced by implementing more than one rotor into the configuration either horizontally or vertically oriented relative to each other. This is analogous to connecting multiple pumps in parallel or in series. The present study will numerically investigate the performance of various configurations of the viscous micropumps with multiple rotors, namely, the dual-horizontal rotor, triple-horizontal rotor, symmetrical dual-vertical rotor, and eight-shaped dual-vertical rotor. The development of drag-and-lift forces with time, as well as the viscous resisting torque on the cylinders were studied. In addition, the corresponding drag, lift, and moment coefficients were calculated. The flow pattern and pressure distribution on the cylinders’ surfaces are also included in the study. Results show that the symmetrical dual-vertical rotor configuration yields the best efficiency and generates the highest flow rate. The steady-state performance of the single-stage micropump was compared to the available experimental and numerical data and found to be in very good agreement. This work provides a foundation for future research on the subject of fluid phenomena in viscous micropumps.

Automated vitrification of mammalian embryos on a digital microfluidic device

We introduce a new model for contact angle saturation phenomenon in electrowetting on dielectric systems. This new model attributes contact angle saturation to repulsion between trapped charges on the cap and base surfaces of the droplet in the vicinity of the three-phase contact line, which prevents these surfaces from converging during contact angle reduction. This repulsion-based saturation is similar to repulsion between charges accumulated on the surfaces of conducting droplets which causes the well known Coulombic fission and Taylor cone formation phenomena. In our model, both the droplet and dielectric coating were treated as lossy dielectric media (i.e., having finite electrical conductivities and permittivities) contrary to the more common assumption of a perfectly conducting droplet and perfectly insulating dielectric. We used theoretical analysis and numerical simulations to find actual charge distribution on droplet surface, calculate repulsion energy, and minimize energy of the total system as a function of droplet contact angle. Resulting saturation curves were in good agreement with previously reported experimental results. We used this proposed model to predict effect of changing liquid properties, such as electrical conductivity, and system parameters, such as thickness of the dielectric layer, on the saturation angle, which also matched experimental results.

Partially filled electrodes for digital microfluidic devices

This paper presents the development of a digital microfluidic device to achieve automated sample preparation for the vitrification of mammalian embryos for clinical in vitro fertilization (IVF) applications. Individual micro droplets manipulated on a digital microfluidic device were used as micro-vessels to transport a single embryo through a complete vitrification procedure. The device showed cell survival and development rates of 77% and 90%, respectively, which are comparable to the control groups that were manually processed.