The timely detection and diagnosis of diseases and accurate monitoring of specific genetic conditions require rapid and accurate separation, sorting, and direction of target cell types toward a sensor device surface. In that regard, cellular manipulation, separation, and sorting are progressively finding application potential within various bioassay applications such as medical disease diagnosis, pathogen detection, and medical testing. The aim of this paper is to present the design and development of a simple traveling wave ferro-microfluidic device and system rig purposed for the potential manipulation and magnetophoretic separation of cells in water-based ferrofluids. This paper details in full: (1) a method for tailoring cobalt ferrite nanoparticles for specific diameter size ranges (10–20 nm), (2) the development of a ferro-microfluidic device for potentially separating cells and magnetic nanoparticles, (3) the development of a water-based ferrofluid with magnetic nanoparticles and non-magnetic microparticles, and (4) the design and development of a system rig for producing the electric field within the ferro-microfluidic channel device for magnetizing and manipulating nonmagnetic particles in the ferro-microfluidic channel. The results reported in this work demonstrate a proof of concept for magnetophoretic manipulation and separation of magnetic and non-magnetic particles in a simple ferro-microfluidic device. This work is a design and proof-of-concept study. The design reported in this model is an improvement over existing magnetic excitation microfluidic system designs in that heat is efficiently removed from the circuit board to allow a range of input currents and frequencies to manipulate non-magnetic particles. Although this work did not analyze the separation of cells from magnetic particles, the results demonstrate that non-magnetic (surrogates for cellular materials) and magnetic entities can be separated and, in some cases, continuously pushed through the channel based on amperage, size, frequency, and electrode spacing. The results reported in this work establish that the developed ferro-microfluidic device may potentially be used as an effective platform for microparticle and cellular manipulation and sorting.
This paper outlines results for a mathematical drug transport model developed for simulating the transport of a hydrophobic drug in a drug eluting stented coronary arterial vessel wall. The mathematical drug transport model incorporates the diffusion equation with a two species (free and bound drug) reversible equilibrium reaction source term to account for tissue binding. The model is solved by an explicit 2-D finite difference method for discretizing and solving the free and bound convection equations with anisotropic vascular drug diffusivities. The relative reaction rates control the interconversion of drug between the free and bound states. Results include provide a glance at the relative distribution of the two drug forms in a two-dimensional model of the arterial vessel wall. The model also reveals how a single species drug delivery model cannot accurately predict the distribution of bound drug.
Cell counting and sorting is a vital step in the purification process within the area of biomedical research. It has been widely reported and accepted that the use of hydrodynamic focusing in conjunction with the application of a dielectrophoretic (DEP) force allows efficient separation of biological entities such as platelets from red blood cell (RBC) samples due to their size difference. This paper presents computational results of a multiphysics simulation modelling study on evaluating continuous separation of RBCs and platelets in a microfluidic device design with saw-tooth profile electrodes via DEP. The theoretical cell particle trajectory, particle cell counting, and particle separation distance study results reported in this work were predicted using COMSOL v6.0 Multiphysics simulation software. To validate the numerical model used in this work for the reported device design, we first developed a simple y-channel microfluidic device with square “in fluid” electrodes similar to the design reported previously in other works. We then compared the obtained simulation results for the simple y-channel device with the square in fluid electrodes to the reported experimental work done on this simple design which resulted in 98% agreement. The design reported in this work is an improvement over existing designs in that it can perform rapid separation of RBCs (estimated 99% purification) and platelets in a total time of 6–7 s at a minimum voltage setting of 1 V and at a minimum frequency of 1 Hz. The threshold for efficient separation of cells ends at 1000 kHz for a 1 V setting. The saw-tooth electrode profile appears to be an improvement over existing designs in that the sharp corners reduced the required horizontal distance needed for separation to occur and contributed to a non-uniform DEP electric field. The results of this simulation study further suggest that this DEP separation technique may potentially be applied to improve the efficiency of separation processes of biological sample scenarios and simultaneously increase the accuracy of diagnostic processes via cell counting and sorting.
This paper presents the development of a computational model for analyzing the magnetic field, particle dynamics, and capture efficiency of magnetic and non-magnetic microparticles in a ferro-magnetic microfluidic system. This computational model demonstrates a proof-of-concept of a method for greatly enhancing magnetic bio-separation in microfluidic systems using an array of conductive elements arranged in quadrature. In contrast to previous works, our approach theoretically uses a microfluidic device with an electronic chip platform consisting of integrated copper electrodes that carry currents to generate programmable magnetic field gradients locally. In practice, alternating currents would be applied to the electrodes in quadrature to create a periodic magnetic field pattern that travels along the length of the microchannel. This work is a phase 1 study that analyzes particle dynamics in a static magnetic field. The model, which is described in more detail in the methods section, combines a Eulerian-Lagrangian and two-way particle-fluid coupling CFD analysis with closed-form magnetic field analysis that be used to predict magnetic separation considering dominant magnetic and hydrodynamic forces similar to our previous work in magnetic drug targeting. The result of this analysis show that the proposed magnetic capture configuration provides substantially enhanced particle capture efficiency relative to conventional systems.
This paper presents the theory and development, validation, and results of a transient computational multi-physics model for analyzing the magnetic field, particle dynamics, and capture efficiency of magnetic and non-magnetic (e.g., Red Blood Cells and E. Coli bacteria) microparticles in a travelling wave ferro-magnetic microfluidic device. This computational model demonstrates proof-of-concept of a method for greatly enhancing magnetic bio-separation in ferro-microfluidic systems using an array of copper conductive elements arranged in quadrature to create a periodic potential energy landscape. In contrast to previous works, our approach theoretically uses a microfluidic device with an electronic chip platform consisting of integrated copper electrodes that carry currents to generate programmable magnetic field gradients locally. Alternating currents are applied to the electrodes in quadrature (using a 90° phase change from the neighboring electrode) to create a periodic magnetic field pattern that travels along the length of the microchannel. Our previous work evaluated magnetic and non-magnetic particles in a static magnetic field within the same channel geometry. This work is a phase 2 study that expands on the previous work and analyzes the dynamics of magnetic and non-magnetic entities characterized by material magnetic susceptibility in a transient magnetic field. This is an improvement over our previous work. The model, which is described in more detail in the methods section, combines a Eulerian-Lagrangian and two-way particle-fluid coupling CFD analysis with closed-form magnetic field analysis that is used to predict magnetic separation considering dominant magnetic and hydrodynamic forces similar to our previous works in magnetic drug targeting. The model was also validated with an experimental low frequency stationary flow study on separating non-magnetic latex fluorescent particles in a water based ferrofluid. The results from the experimental study and the developed model demonstrates that the proposed device may potentially be used as an effective platform for microparticle and cellular manipulation and sorting. The developed multi-physics model could potentially be used as a design optimization tool for traveling wave ferro-microfluidic devices.
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