Three-Dimensional Reservoir-Based Dielectrophoresis (rDEP) for Enhanced Particle Enrichment.

Selective enrichment of target species is crucial for a wide variety of engineering systems for improved performance of subsequent processes. Dielectrophoresis (DEP) is a powerful electrokinetic method that can be used to focus, trap, concentrate, and separate a variety of species in a label-free manner. The commonly employed methods for DEP suffer from limitations such as electrode fouling and high susceptibility to Joule heating effects. Recently, our group has demonstrated DEP-based manipulations of particles and cells using a novel method of reservoir-based dielectrophoresis (rDEP) which exploits the naturally produced electric field gradients at the reservoir-microchannel junction. Although this method reasonably addresses the limitations mentioned above while maintaining a high simplicity of fabrication, all of our demonstrations so far have used a two-dimensional rDEP, which limits the performance of the devices. This work aims to improve their performance further by making the DEP three-dimensional. Through detailed experimental and numerical analysis, we demonstrate a six-fold increase in the enrichment performance of latex beads and a significant reduction in the power consumption for the new devices, which would allow a more reliable integration of the same into micro-total analysis systems.

Joule heating effects on electroosmotic entry flow.

Electroosmotic flow is the transport method of choice in microfluidic devices over traditional pressure-driven flow. To date, however, studies on electroosmotic flow have been almost entirely limited to inside microchannels. This work presents the first experimental study of Joule heating effects on electroosmotic fluid entry from the inlet reservoir (i.e., the well that supplies fluids and samples) to the microchannel in a polymer-based microfluidic chip. Electrothermal fluid circulations are observed at the reservoir-microchannel junction, which grow in size and strength with the increasing alternating current to direct current voltage ratio. Moreover, a 2D depth-averaged numerical model is developed to understand the effects of Joule heating on fluid temperature and flow fields in electrokinetic microfluidic chips. This model overcomes the problems encountered in previous unrealistic 2D and costly 3D models, and is able to predict the observed electroosmotic entry flow patterns with a good agreement.

Enhanced Throughput for Electrokinetic Manipulation of Particles and Cells in a Stacked Microfluidic Device.

Electrokinetic manipulation refers to the control of particle and cell motions using an electric field. It is an efficient technique for microfluidic applications with the ease of operation and integration. It, however, suffers from an intrinsic drawback of low throughput due to the linear dependence of the typically very low fluid permittivity. We demonstrate in this work a significantly enhanced throughput for electrokinetic manipulation of particles and cells by the use of multiple parallel microchannels in a two-layer stacked microfluidic device. The fabrication of this device is simple without the need of a precise alignment of the two layers. The number of layers and the number of microchannels in each layer can thus be further increased for a potentially high throughput electrokinetic particle and cell manipulations.

Outcomes of using omalizumab for more than 1 year in refractory chronic urticaria.

BACKGROUND: Because omalizumab was only recently approved for refractory chronic urticaria (CU), there are few studies that have evaluated patients using omalizumab for longer than 1 year. OBJECTIVE: To evaluate omalizumab's effectiveness, its feasibility in weaning, and its safety profile in patients with refractory CU who were on omalizumab for longer than 1 year. METHODS: A retrospective chart review was conducted of adults with well-defined refractory CU in the authors' clinic from October 2005 to January 2015 who responded to omalizumab and who had taken it for longer than 1 year. In addition to baseline characteristics, the duration, course, and adverse effects of omalizumab therapy were analyzed. RESULTS: Eight of 10 patients had complete resolution of symptoms after reaching their optimal regimen and had taken omalizumab for a median duration of 37 months (17-112 months). None of them required uptitration of dosage, an increase in frequency of dosage, or add-on therapy. Five of 8 patients, while being tapered, had recurrence of symptoms requiring the reuse of omalizumab. One successfully discontinued omalizumab, 1 was in the process of being weaned but did not experience a flare, and 1 had not attempted weaning. CONCLUSION: This study from the United States suggests that omalizumab is effective and safe in patients with refractory CU who use omalizumab for longer than 1 year. Periodic attempts at weaning patients with CU from omalizumab should be attempted because there could be a chance of spontaneous remission. This might be difficult because symptoms are likely to recur, but restarting omalizumab in these patients seems effective and safe.

Electrokinetic preconcentration of particles and cells in microfluidic reservoirs.

Preconcentrating samples of dilute particles or cells to a detectable level is required in many chemical, environmental and biomedical applications. A variety of force fields have thus far been demonstrated to capture and accumulate particles and cells in microfluidic devices, which, however, all take place within the region of microchannels and may potentially cause channel clogging. This work presents a new method for the electrokinetic preconcentration of 1 µm-diameter polystyrene particles and E. coli cells in a very-low-conductivity medium inside a microfluidic reservoir. The entire microchannel can hence be saved for a post-concentration analysis. This method exploits the strong recirculating flows of induced-charge electroosmosis to concentrate particles and cells near the corners of the reservoir-microchannel interface. Positive dielectrophoresis is found to also play a role when small microchannels are used at high electric fields. Such an in-reservoir electrokinetic preconcentration method can be easily implemented in a parallel mode to increase the flow throughput, which may potentially be used to preconcentrate bacterial pathogens in water.

An unexpected particle oscillation for electrophoresis in viscoelastic fluids through a microchannel constriction.

Electrophoresis plays an important role in many applications, which, however, has so far been extensively studied in Newtonian fluids only. This work presents the first experimental investigation of particle electrophoresis in viscoelastic polyethylene oxide (PEO) solutions through a microchannel constriction under pure DC electric fields. An oscillatory particle motion is observed in the constriction region, which is distinctly different from the particle behavior in a polymer-free Newtonian fluid. This stream-wise particle oscillation continues until a sufficient number of particles form a chain to pass through the constriction completely. It is speculated that such an unexpected particle oscillating phenomenon is a consequence of the competition between electrokinetic force and viscoelastic force induced in the constriction. The electric field magnitude, particle size, and PEO concentration are all found to positively affect this viscoelasticity-related particle oscillation due to their respective influences on the two forces.

Microfluidic electrical sorting of particles based on shape in a spiral microchannel.

Shape is an intrinsic marker of cell cycle, an important factor for identifying a bioparticle, and also a useful indicator of cell state for disease diagnostics. Therefore, shape can be a specific marker in label-free particle and cell separation for various chemical and biological applications. We demonstrate in this work a continuous-flow electrical sorting of spherical and peanut-shaped particles of similar volumes in an asymmetric double-spiral microchannel. It exploits curvature-induced dielectrophoresis to focus particles to a tight stream in the first spiral without any sheath flow and subsequently displace them to shape-dependent flow paths in the second spiral without any external force. We also develop a numerical model to simulate and understand this shape-based particle sorting in spiral microchannels. The predicted particle trajectories agree qualitatively with the experimental observation.

Joule heating effects on reservoir-based dielectrophoresis.

Reservoir-based dielectrophoresis (rDEP) is a recently developed technique that exploits the inherent electric field gradients at a reservoir-microchannel junction to focus, trap, and sort particles. However, the locally amplified electric field at the junction is likely to induce significant Joule heating effects that are not considered in previous studies. This work investigates experimentally and numerically these effects on particle transport and control in rDEP processes in PDMS/PDMS microchips. It is found that Joule heating effects can reduce rDEP focusing considerably and may even disable rDEP trapping. This is caused by the fluid temperature rise at the reservoir-microchannel junction, which significantly increases the local particle velocity due to fluid flow and particle electrophoresis while has a weak impact on the particle velocity due to rDEP. The numerical predictions of particle stream width and electric current, which are the respective indicators of rDEP manipulation and fluid temperature, are demonstrated to both match the experimental measurements with a good accuracy.

Reservoir-based dielectrophoresis for microfluidic particle separation by charge.

The separation of particles from a complex mixture is important to a wide range of applications in industry, biology, medicine etc. This work demonstrates a microfluidic approach to separate similar-sized fluorescent and nonfluorescent particles based upon the difference in their surface charges inside a reservoir. Such a separation exploits the reservoir-based dielectrophoresis, which is induced by the inherent electric field gradient formed at the reservoir-microchannel junction, to isolate the trapped fluorescent particles within the reservoir from the streaming nonfluorescent particles. The effects of the DC field magnitude (or equivalently the electrokinetic flow magnitude) and the AC field frequency of DC-biased AC electric fields are investigated on particle separation. A numerical model is also developed to simulate the electrokinetic transport behaviors of the two types of particles. This demonstrated reservoir-based dielectrophoresis particle sorter can operate in parallel to increase the flow throughput. It is suitable for integration with other functional parts into lab-on-a-chip devices for diverse particle handling.

Numerical modeling of Joule heating effects in insulator-based dielectrophoresis microdevices.

Insulator-based DEP (iDEP) has been established as a powerful tool for manipulating particles in microfluidic devices. However, Joule heating may become an issue in iDEP microdevices due to the local amplification of electric field around the insulators. This results in an electrothermal force that can manifest itself in the flow field in the form of circulations, thus affecting the particle motion. We develop herein a transient, 3D, full-scale numerical model to study Joule heating and its effects on the coupled transport of charge, heat, and fluid in an iDEP device with a rectangular constriction microchannel. This model is validated by comparing the simulation results with the experimentally obtained fluid flow patterns and particle images that were reported in our recent works. It identifies a significant difference in the time scales of the electric, temperature, and flow fields in iDEP microdevices. It also predicts the locations of electrothermal flow circulations in different halves of the channel at the upstream and downstream of the constriction.

Microfluidic separation of live and dead yeast cells using reservoir-based dielectrophoresis.

Separating live and dead cells is critical to the diagnosis of early stage diseases and to the efficacy test of drug screening, etc. This work demonstrates a novel microfluidic approach to dielectrophoretic separation of yeast cells by viability. It exploits the cell dielectrophoresis that is induced by the inherent electric field gradient at the reservoir-microchannel junction to selectively trap dead yeast cells and continuously separate them from live ones right inside the reservoir. This approach is therefore termed reservoir-based dielectrophoresis (rDEP). It has unique advantages as compared to existing dielectrophoretic approaches such as the occupation of zero channel space and the elimination of any mechanical or electrical parts inside microchannels. Such an rDEP cell sorter can be readily integrated with other components into lab-on-a-chip devices for applications to biomedical diagnostics and therapeutics.

Hantavirus pulmonary syndrome.

Hantavirus pulmonary syndrome, also known as hantavirus cardiopulmonary syndrome, is a recently described infectious syndrome found throughout the Americas. Although infection is sporadic and uncommon compared with other atypical pneumonia syndromes, its high mortality rate warrants the maintenance of a high index of suspicion in rural settings. Because no specific therapies are available for the disease, prevention and early recognition play an important role in reducing mortality from the disease. This article reviews the nature of the viruses that cause hantavirus pulmonary syndrome, the epidemiology and ecology of disease transmission, and disease recognition, treatment, and prevention.