The majority of microfluidic technologies for cell sorting and isolation involve bifurcating (e.g., Y- or T-shaped junction) microchannels to trap the cells of a specific type. However, the microfluidic trapping efficiency remains low, independently of whether the cells are separated by a passive or an active sorting method. Using a custom computational algorithm, we studied the migration of separated deformable cells in a Y-junction microchannel, with a bifurcation angle ranging from 30° to 180°. Single or two cells of initially spherical shape were considered under flow conditions corresponding to inertial microfluidics. Through the numerical simulation, we identified the effects of cell size, cytoplasmic viscoelasticity, cortical tension, flow rate, and bifurcation angle on the critical separation distance for cell trapping. The results of this study show that the trapping and isolation of blood cells, and circulating tumor cells in a Y-junction microchannel was most efficient and least dependent on the flow rate at the bifurcation angle of 120°. At this angle, the trapping efficiency for white blood cells and circulating tumor cells increased, respectively, by 46% and 43%, in comparison with the trapping efficiency at 60°. The efficiency to isolate invasive tumor cells from noninvasive ones increased by 32%. This numerical study provides important design criteria to optimize microfluidic technology for deformability-based cell sorting and isolation.

One of the promising approaches for high-throughput screening of cell mechanotype is microfluidic deformability cytometry (mDC) in which the apparent deformation index (DI) of the cells stretched by extensional flow at the stagnation point of a cross-slot microchannel is measured. The DI is subject to substantial measurement errors due to cell offset from the flow centerline and velocity fluctuations in inlet channels, leading to artificial widening of DI vs. cell size plots. Here, we simulated an mDC experiment using a custom computational algorithm for viscoelastic cell migration. Cell motion and deformation in a cross-slot channel was modeled for fixed or randomized values of cellular mechanical properties (diameter, shear elasticity, cortical tension) and initial cell placement, with or without sinusoidal fluctuations between the inlet velocities. Our numerical simulation indicates that mDC loses sensitivity to changes in shear elasticity when the offset distance exceeds 5 μm, and just 1% velocity fluctuation causes an 11.7% drop in the DI. The obtained relationships between the cell diameter, shear elasticity, and offset distance were used to establish a new measure of cell deformation, referred to as "Elongation Index" (EI). In the randomized study, the EI scatter plots were visibly separated for the low and high elasticity populations of cells, with a mean of 300 and 3,500 Pa, while the standard DI output was unable to distinguish between these two groups of cells. The successful suppression of the offset artefacts with a narrower data distribution was shown for the EI output of MCF-7 cells.

Embedded pillar microstructures are an efficient approach for controlling and sculpting shear flow in a microchannel but have not yet demonstrated to be effective for deformability-based cell separation and sorting. Although simple pillar configurations (lattice, line sequence) worked well for size-based separation of rigid particles, they had a low separation efficiency for circulating cells. The objective of this study was to optimize sequenced microstructures for the separation of deformable cells. This was achieved by numerical analysis of pairwise cell migration in a microchannel with multiple pillars, which size, longitudinal spacing, and lateral location, as well as the cell elasticity and size, varied. This study revealed two basic pillar configurations optimized for deformability-based separation: 1) 'duplet' that consists of two closely spaced pillars positioned far below the centerline and above the centerline halfway to the wall; and 2) 'triplet' composed of three widely-spaced pillars located below, above and at the centerline, respectively. The duplet configuration is well suited for deformable cell separation in short channels, while the triplet or a combination of duplets and triplets provides even better separation in long channels. These optimized pillar microstructures can dramatically improve microfluidic methods for sorting and isolation of blood and rare circulating tumor cells.

Objectives: Atherosclerotic plaque progression within the carotid artery is thought to be due to a combination of a proinflammatory state and various hemodynamic conditions, including wall shear stresses (WSS) and vascular strain. We aimed to create a computational model of the carotid artery from carotid noninvasive imaging scans to evaluate the effects of plaque composition and artery and plaque geometry by fluid dynamics.Methods: A computational model was created from an institutional database of patients who underwent carotid endarterectomy (CEA). Patients underwent duplex ultrasonography (DUS) and computed tomography angiography (CTA) of the carotid before intervention. CTA images were evaluated in a 3D imaging software for vessel and plaque geometry; plaque composition was based on Hounsfield units (HU) from CTA scans. The geometric data were then transported into a 3D processing software (ScanIP+FE), where a patient-specific computational mesh was created. This software allowed conversion of HU into mass density based on previously validated models. This mesh was then transferred to a Multiphysics software where a model was created from the mesh. The velocity curves, obtained from preoperative DUS of the common (CCA), internal (ICA) and external (ECA) carotid artery were used to set the inlet boundaries. Outlet and pressure boundaries were created to simulate the physiologic conditions of the carotid artery. In order to evaluate velocity streamlines by time, WSS, and volumetric strain along the carotid artery, the model was subjected to dynamic fully coupled, fluid-structure time-simulation through one cardiac cycle.Results: 3D geometry analysis reveals the different mass densities in the ICA plaque (Fig, A). Time-dependent analysis of an asymptomatic patient-specific computational model demonstrated increased velocities in the stenotic portion (Fig, B) and incremental increases in WSS along the ICA lesion. The highest WSS was located at the site of the greatest plaque burden (shoulder region of the ICA ; Fig, D). Volumetric strain was found to be lowest at the site of the greatest stenosis (Fig, C), related to the highest degree of calcification, due to less deformation and higher material density of the plaque.Conclusions: Time-dependent fluid simulations from this novel model add to previously validated results from prior computational models in biomedical engineering. The benefit of a patient-specific model creation has the potential to compare changes in WSS and shear strain at various points across individual carotid plaques. In the future, computational differences between asymptomatic and acutely symptomatic patients may reveal key patientspecific features indicative of plaque vulnerability.Objectives: Drug-coated balloons have been recently approved for clinical use in the U.S. The balloons make use of a burst release, but given that many patients with peripheral arterial disease have multiple lesions, a drug-coated balloon that allows for sustained drug delivery over several minutes could be adva...

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