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.
Abstract. Optical coherence tomography images of human thoracic aorta from aneurysms reveal elastin disorders and smooth muscle cell alterations when visualizing the media layer of the aortic wall. These disorders can be employed as indicators for wall degradation and, therefore, become a hallmark for diagnosis of risk of aneurysm under intraoperative conditions. Two approaches are followed to evaluate this risk: the analysis of the reflectivity decay along the penetration depth and the textural analysis of a two-dimensional spatial distribution of the aortic wall backscattering. Both techniques require preprocessing stages for the identification of the air-sample interface and for the segmentation of the media layer. Results show that the alterations in the media layer of the aortic wall are better highlighted when the textural approach is considered and also agree with a semiquantitative histopathological grading that assesses the degree of wall degradation. The correlation of the co-occurrence matrix attains a sensitivity of 0.906 and specificity of 0.864 when aneurysm automatic diagnosis is evaluated with a receiver operating characteristic curve. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Degradation of the wall of human ascending thoracic aorta has been assessed through Optical Coherence Tomography (OCT). OCT images of the media layer of the aortic wall exhibit micro-structure degradation in case of diseased aortas from aneurysmal vessels. The OCT indicator of degradation depends on the dimension of areas of the media layer where backscattered reflectivity becomes smaller due to a disorder on the morphology of elastin, collagen and smooth muscle cells (SMCs). Efficient pre-processing of the OCT images is required to accurately extract the dimension of degraded areas after an optimized thresholding procedure. OCT results have been validated against conventional histological analysis. The OCT qualitative assessment has achieved a pair sensitivity-specificity of 100%-91.6% in low-high degradation discrimination when a threshold of 4965.88µm 2 is selected. This threshold suggests to have physiological meaning. The OCT quantitative evaluation of degradation achieves a correlation of 0.736 between the OCT indicator and the histological score. This in-vitro study can be transferred to the clinical scenario to provide an intraoperative assessment tool to guide cardiovascular surgeons in open repair interventions.
Prototyping hyperspectral imaging devices in current biomedical optics research requires taking into consideration various issues regarding optics, imaging, and instrumentation. In summary, an ideal imaging system should only be limited by exposure time, but there will be technological limitations (e.g., actuator delay and backlash, network delays, or embedded CPU speed) that should be considered, modeled, and optimized. This can be achieved by constructing a multiparametric model for the imaging system in question. The article describes a rotating-mirror scanning hyperspectral imaging device, its multiparametric model, as well as design and calibration protocols used to achieve its optimal performance. The main objective of the manuscript is to describe the device and review this imaging modality, while showcasing technical caveats, models and benchmarks, in an attempt to simplify and standardize specifications, as well as to incentivize prototyping similar future designs.
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