A Model for Predicting Magnetic Targeting of Multifunctional Particles in the Microvasculature

A mathematical model is presented for predicting magnetic targeting of multifunctional carrier particles that are designed to deliver therapeutic agents to malignant tissue in vivo. These particles consist of a nonmagnetic core material that contains embedded magnetic nanoparticles and therapeutic agents such as photodynamic sensitizers. For in vivo therapy, the particles are injected into the vascular system upstream from malignant tissue, and captured at the tumor using an applied magnetic field. The applied field couples to the magnetic nanoparticles inside the carrier particle and produces a force that attracts the particle to the tumor. In noninvasive therapy the applied field is produced by a permanent magnet positioned outside the body. In this paper a mathematical model is developed for predicting noninvasive magnetic targeting of therapeutic carrier particles in the microvasculature. The model takes into account the dominant magnetic and fluidic forces on the particles and leads to an analytical expression for predicting their trajectory. An analytical expression is also derived for predicting the volume fraction of embedded magnetic nanoparticles required to ensure capture of the carrier particle at the tumor. The model enables rapid parametric analysis of magnetic targeting as a function of key variables including the size of the carrier particle, the properties and volume fraction of the embedded magnetic nanoparticles, the properties of the magnet, the microvessel, the hematocrit of the blood and its flow rate.Comment: To appear in Journal of Magnetism and Magnetic Material

Free-space Excitation of Resonant Cavities formed from Cloaking Metamaterial

We propose a new class of resonant electromagnetic structures, and study their response to free-space illumination. The structures consist of partial cylindrical shells that have cloaking material properties proposed by Pendry et al. These metamaterial shells have apertures that allow the propagation of incident irradiation into an interior resonant cavity. We use full wave time-harmonic analysis to study the field distribution inside the cavity, and show that an analogue of Whispering Gallery Modes (WGMs) can be efficiently excited via free-space illumination.Comment: to appear J. Modern Optic

Electromagnetic Enhancement in Lossy Optical Transition Metamaterials

We investigate the effect of anomalous field enhancement in metamaterials where the effective refractive index gradually changes from positive to negative values, i.e. transition metamaterials. We demonstrate that considerable field enhancement can be achieved in lossy optical transition metamaterials that have electromagnetic material properties obtained from experimental data. The field enhancement factor is found to be polarization-dependent and largely determined by the material parameters and the width of the transition layer

Computational modeling and fluorescence microscopy characterization of a two-phase magnetophoretic microsystem for continuous-flow blood detoxification

Magnetic beads can be functionalized to capture and separate target pathogens from blood for extracorporeal detoxification. The beads can be magnetically separated from a blood stream and collected into a coflowing buffer solution using a two-phase liquid-liquid continuous-flow microfluidic device in the presence of an external field. However, device design and process optimization, i.e. high bead recovery with minimum blood loss or dilution remain a substantial technological challenge. We introduce a CFD-based Eulerian-Lagrangian computational model that enables the rational design and optimization of such systems. The model takes into account dominant magnetic and hydrodynamic forces on the beads as well as coupled bead-fluid interactions. Fluid flow (Navier-Stokes equations) and mass transfer (Fick's law) between the coflowing fluids are solved numerically, while the magnetic force on the beads is predicted using analytical methods. The model is demonstrated via application to a prototype device and used to predict key performance metrics; degree of bead separation, flow patterns, and mass transfer, i.e. blood diffusion to the buffer phase. The impact of different process variables and parameters-flow rates, bead and magnet dimensions and fluid viscosities-on both bead recovery and blood loss or dilution is quantified for the first time. The performance of the prototype device is characterized using fluorescence microscopy and the experimental results are found to match theoretical predictions within an absolute error of 15%. While the model is demonstrated here for analysis of a detoxification device, it can be readily adapted to a broad range of magnetically-enabled microfluidic applications, e.g. bioseparation, sorting and sensing

Numerical analysis of bead magnetophoresis from flowing blood in a continuous-flow microchannel: implications to the bead-fluid interactions

In this work, we report a numerical flow-focused study of bead magnetophoresis inside a continuous-flow microchannel in order to provide a detailed analysis of bead motion and its effect on fluid flow. The numerical model involves a Lagrangian approach and predicts the bead separation from blood and their collection into a flowing buffer by the application of a magnetic field generated by a permanent magnet. The following scenarios are modelled: (i) one-way coupling wherein momentum is transferred from the fluid to beads, which are treated as point particles, (ii) two-way coupling wherein the beads are treated as point particles and momentum is transferred from the bead to the fluid and vice versa, and (iii) two-way coupling taking into account the effects of bead volume in fluid displacement. The results indicate that although there is little difference in the bead trajectories for the three scenarios, there is significant variation in the flow fields, especially when high magnetic forces are applied on the beads. Therefore, an accurate full flow-focused model that takes into account the effects of the bead motion and volume on the flow field should be solved when high magnetic forces are employed. Nonetheless, when the beads are subjected to medium or low magnetic forces, computationally inexpensive models can be safely employed to model magnetophoresis.Financial support from the Spanish Ministry of Economy and Competitiveness under the projects CTQ2015-72364-EXP and CTQ2015-66078-R (MINECO/FEDER) is gratefully acknowledged. Jenifer Gómez-Pastora also thanks the FPI postgraduate research grant (BES-2013-064415). Edward P. Furlani gratefully acknowledges fnancial support from the U.S. National Science Foundation, through Award CBET-1337860

Aqueous ferrofluid of magnetite nanoparticles: Fluores- cence labeling and magnetophoretic control

A method is presented for the preparation of a biocompatible ferrofluid containing dye-functionalized magnetite nanoparticles that can serve as fluorescent markers. This method entails the surface functionalization of magnetite nanoparticles using citric acid to produce a stable aqueous dispersion and the subsequent binding of fluorescent dyes to the surface of the particles. Several ferrofluid samples were prepared and characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), BET surface area analysis, transmission electron microscopy (TEM), and SQUID magnetometry. In addition, confocal fluorescence microscopy was used to study the response of the fluorescent nanoparticles to an applied magnetic field and their uptake by cells in vitro. Results are presented on the distribution of particle sizes, the fluorescent and magnetic properties of the nanoparticles, and the nature of their surface bonds. Biocompatible ferrofluids with fluorescent nanoparticles enable optical tracking of basic processes at the cellular level combined with magnetophoretic manipulation and should be of substantial value to researchers engaged in both fundamental and applied biomedical research

Analysis of an Electrostatic MEMS Squeeze-film Drop Ejector

We present an analysis of an electrostatic drop-on-demand MEMS fluid ejector. The ejector consists of a microfluidic chamber with a piston that is suspended a few microns beneath a nozzle plate. A drop is ejected when a voltage is applied between the orifice plate and the piston. This produces an electrostatic force that moves the piston towards the nozzle. The moving piston generates a squeeze-film pressure distribution that causes drop ejection. We discuss the operating physics of the ejector and present a lumped-element model for predicting its performance. We calibrate the model using coupled structural-fluidic CFD analysis

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Abstract: We present a study of an optofluidic biosensor. The sensor operates in a transmission mode wherein detection is based on a shift in the transmission spectrum caused by the contrast in refractive index between the carrier fluid and the target biomaterial. We study the behavior of the sensor using 2D full-wave electromagnetic analysis, and perform parametric studies of sensitivity as a function of key device parameters