The Ohio State University,
Keywords: magnetophoresis, microfluidics, CFD, blood detoxification
Summary:Magnetic beads have been extensively used in the last decades as a consequence of the advantages these smart and tailor-made materials present. One of their most important properties is their superparamagnetic characteristics as well as the possible functionalization to capture and separate target biomolecules. In fact, these materials have been successfully employed for capturing harmful pathogens from blood for a high number of clinical conditions. Once the capture of the pathogen is complete, the magnetic separation of the beads bound to these pathogens is required. Different microfluidic separators have been proposed for this process; however, continuous-flow devices are reported as the best candidates due to their multiple advantages. In continuous separators, the beads are magnetically separated from the bloodstream and collected into a co-flowing buffer solution when an external magnetic field provided by a magnet is applied. However, device design and process optimization, i.e. high bead recovery with minimum blood loss or dilution remain a substantial technological challenge. In this contribution, accurate fluidic and magnetic computational models are presented for magnetic particle separation in continuous-flow microfluidic bioseparators. The models take 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 co-flowing fluids are solved numerically, while the magnetic force on the beads is predicted using the analytical model developed by Dr. Ed Furlani (3). The models are demonstrated via application to prototype devices 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%. Moreover, the models were used to study critical details of the separation process, including the trajectories of individual particles, the time required for the separation, and the perturbation of the blood/buffer co-flows (i.e., instability of the blood/buffer interface). Overall, it is concluded that the modeling effort presented in this contribution enables understanding of the fundamental physical phenomena involved in the separation process, while offering an ideal parametric analysis and optimization platform, thereby facilitating the development of novel magnetophoretic microsystems not only for blood detoxification processes but also for many other biomedical applications that involve multiple confined liquid phases. Finally, I would like to express my most sincere gratitude to Dr. Ed Furlani for his invaluable contributions to this work, to whom I will be eternally grateful.