Hydrodynamic focusing of an elastic capsule in stokes flow: An exploratory numerical study

We study numerically the motion of an elastic capsule in a simple microfluidic device, a sheath flow focuser, designed to align (or focus) particles at the center of a microchannel. The geometry of the device is given, while the flow conditions are varied, and the outflux is constant. The efficiency is expressed in terms of the distance required to achieve focusing and the functioning is characterized by the deformations and stresses undergone by the capsule membrane. Calculations are performed for a ‘stiff’ and ‘soft’ capsule, corresponding to a capillary number equal to Ca = 0.05 and Ca = 0.3 based on the outflow rate. We report that as the sheath flow is increased the focusing efficiency grows and plateaus beyond a certain threshold, displaying a drop in the efficiency gain. Differently, the deformations and stresses undergone by the capsule membrane grow for the entire range of the flow parameters considered. This should be kept in mind if the stresses exerted on the membrane have to be minimized or need to be below certain characteristic thresholds typical of the specific application considered. Especially large initial offsets and stiff capsules benefit from focusing

Performance of a thrombectomy device for aspiration of thrombus with various sizes based on a computational fluid dynamic modelling

It is important to thoroughly remove the thrombus within the course of aspiration thrombectomy; otherwise, it may lead to further embolization. The performance of the aspiration thrombectomy device with a generic geometry is studied through the computational approach. In order to model the thrombus aspiration, a real left coronary artery is chosen while thrombi with various sizes are located at the bifurcation area of the coronary artery and, depending on the size of the thrombus, it is stretched toward the side branches. The thrombus occupies the artery resembling the blood current obstruction in the coronary vessel similar to the situation that leads to heart attack. It is concluded that the aspiration ability of the thrombectomy device is not linked to the thrombus size; it is rather linked to the aspiration pressure and thrombus age (organized versus fresh thrombus). However, the aspiration time period correlates to the thrombus size. The minimum applicable aspiration pressure is also investigated in this study

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A[subscript 3] adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.National Cancer Institute (U.S.) (Grant R33 CA174550-01)National Cancer Institute (U.S.) (Grant R21 CA140096)Italian Ministry of HealthCharles Stark Draper Laboratory (Fellowship

Automatic segmentation of optical coherence tomography pullbacks of coronary arteries treated with bioresorbable vascular scaffolds: Application to hemodynamics modeling

Automatic algorithms for stent struts segmentation in optical coherence tomography (OCT) images of coronary arteries have been developed over the years, particularly with application on metallic stents. The aim of this study is three-fold: (1) to develop and to validate a segmentation algorithm for the detection of both lumen contours and polymeric bioresorbable scaffold struts from 8-bit OCT images, (2) to develop a method for automatic OCT pullback quality assessment, and (3) to demonstrate the applicability of the segmentation algorithm for the creation of patient-specific stented coronary artery for local hemodynamics analysis

A framework for computational fluid dynamic analyses of patient-specific stented coronary arteries from optical coherence tomography images

The clinical challenge of percutaneous coronary interventions (PCI) is highly dependent on the recognition of the coronary anatomy of each individual. The classic imaging modality used for PCI is angiography, but advanced imaging techniques that are routinely performed during PCI, like optical coherence tomography (OCT), may provide detailed knowledge of the pre-intervention vessel anatomy as well as the post-procedural assessment of the specific stent-to-vessel interactions. Computational fluid dynamics (CFD) is an emerging investigational tool in the setting of optimization of PCI results. In this study, an OCT-based reconstruction method was developed for the execution of CFD simulations of patient-specific coronary artery models which include the actual geometry of the implanted stent. The method was applied to a rigid phantom resembling a stented segment of the left anterior descending coronary artery. The segmentation algorithm was validated against manual segmentation. A strong correlation was found between automatic and manual segmentation of lumen in terms of area values. Similarity indices resulted >96% for the lumen segmentation and >77% for the stent strut segmentation. The 3D reconstruction achieved for the stented phantom was also assessed with the geometry provided by X-ray computed micro tomography scan, used as ground truth, and showed the incidence of distortion from catheter-based imaging techniques. The 3D reconstruction was successfully used to perform CFD analyses, demonstrating a great potential for patient-specific investigations. In conclusion, OCT may represent a reliable source for patient-specific CFD analyses which may be optimized using dedicated automatic segmentation algorithms

A computational and experimental study inside microfluidic systems: the role of shear stress and flow recirculation in cell docking

Abstract In this paper, microfluidic devices containing microwells that enabled cell docking were investigated. We theoretically assessed the effect of geometry on recirculation areas and wall shear stress patterns within microwells and studied the relationship between the computational predictions and experimental cell docking. We used microchannels with 150 μm diameter microwells that had either 20 or 80 μm thickness. Flow within 80 μm deep microwells was subject to extensive recirculation areas and low shear stresses (<0.5 mPa) near the well base; whilst these were only presented within a 10 μm peripheral ring in 20 μm thick microwells. We also experimentally demonstrated that cell docking was significantly higher (p<0.01) in 80 μm thick microwells as compared to 20 μm thick microwells. Finally, a computational tool which correlated physical and geometrical parameters of microwells with their fluid dynamic environment was developed and was also experimentally confirmed

Simulation of stent deployment in a realistic human coronary artery

Background: The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis. Methods: 3D reconstruction of a mildly stenosed coronary artery was carried out based on a combination of biplane angiography and intravascular ultrasound. Finite element method computations were performed to sim

A multiscale model for the study of cardiac biomechanics in single-ventricle surgeries: A clinical case

Complex congenital heart disease characterized by the underdevelopment of one ventricular chamber (single ventricle (SV) circulation) is normally treated with a three-stage surgical repair. This study aims at developing a multiscale computational framework able to couple a patient-specific three-dimensional finite-element model of the SV to a patient-specific lumped parameter (LP) model of thewhole circulation, in a closed-loop fashion. A sequential approach was carried out: (i) cardiocirculatory parameters were estimated by using a fully LP model; (ii) ventricular material parameters and unloaded geometry were identified by means of the stand-alone, three-dimensional model of the SV; and (iii) the three-dimensional model of SV was coupled to the LP model of the circulation, thus closing the loop and creating a multiscale model. Once the patient-specific multiscale model was set using pre-operative clinical data, the virtual surgery was performed, and the post-operative conditions were simulated. This approach allows the analysis of local information on ventricular function aswell as global parameters of the cardiovascular system. This methodology is generally applicable to patients suffering from SV disease for surgical planning at different stages of treatment. As an example, a clinical case from stage 1 to stage 2 is considered here