Research
Cardiovascular flow and related biomechanics
Cardiovascular disease (CVD) is the leading global cause of death. However, modeling accurate biomechanics of cardiovascular system is still challenging since it needs to incorporate both fluid dynamics and valve structural mechanics. I developed a fully-coupled FSI model using smoothed particle hydrodynamics (SPH) to solve the blood flow and finite element (FE) model to capture the nonlinear structural response of a bioprosthetic heart valve (BHV). Comparative simulations were performed to investigate the impact of fluid-structure interaction (FSI) model versus pure-FE model. Only FSI model can capture the realistic leaflet dynamic deformation due to more accurate spatial and temporal loading conditions on the leaflets. For the first time, we found that the water-hammer effect induced by the fluid inertia during the valve closing phase could cause 13-28% higher stress on the leaflets, which is an important finding previously has been ignored in the valve design. The developed FSI model could serve as an effective tool to better assess valve dynamics and optimize the next generation BHV designs.
To extend previous research in a complex left heart (LH) model, we investigated the intraventricular blood flow and structural responses of the coupled aortic and mitral valves in a patient-specific left heart anatomy during the entire cardiac cycle. The complexity of this FSI model was reflected in many aspects, including anisotropic hyperelastic modeling of heart valves based on human material properties, native leaflet and left ventricle geometries segmented from computed tomography (CT) scans, and fully-coupled interaction between the valves and intraventricular blood flow. Comparison of FSI results with patient-specific echocardiography data demonstrates that our FSI model is able to quantitatively predict the leaflet kinematics and the large-scale intraventricular blood flow with a reasonable agreement. Moreover, compared to a simplified LV model without valves, the current FSI model demonstrated the coupling effect of two valves on hemodynamics. The proposed FSI framework has the potential to improve our understanding of cardiovascular physiology and to support medical professionals in clinical decision-making.
Despite transcatheter aortic valve replacement (TAVR) has been recently approved to treat for aortic stenosis in intermediate-risk patients, there remain several potential limitations that need to be minimized. Among them, paravalvular leak (PVL) is a frequent complication of TAVR associated with increased mortality. Currently, there is no effective method to preoperatively predict and prevent PVL. I developed a computational framework utilizing FE and computational fluid dynamics (CFD) to investigate the severity of PVL after TAVR. First, FE model was used to simulate a self-expandable CoreValve deployment into a patient-specific aortic root. Subsequently, CFD simulations were performed based on the post-TAVR geometries from FE simulations, and parametric investigation of the impact of TAV skirt shape, orientation and deployment height on PVL was conducted. The predicted PVL was in good agreement with the echo data. The parametric study provided useful insights to the TAV deployment strategies for individual patient and may facilitate next-generation TAV designs.
Impairment of coronary artery flow is a severe complication of transcatheter aortic valve (TAV) implantation, which can arise due to improper TAV positioning. However, little work has been done to quantify the effects of the TAV positioning on the coronary flow. We developed a realistic in vitro model of coronary artery flow and investigated the impact of TAV deployed orientations on coronary flow. The coronary hemodynamics was first replicated mathematically using a lumped parameter model with time-varying myocardial resistance. Based on the analytical model, two stepper motor controlled stopcock valves were integrated in a left heart simulator to represent the variable myocardial resistance in the experimental setup. The coronary flow and pressure waveforms obtained from the in vitro system were consistent with published data. The measured results demonstrated that TAV orientation does not have a significant impact on the coronary flow. The lumped parameter and experimental models presented may be used in the future to explore more complex TAV deployment scenarios or pathological coronary artery flow conditions.
Links to Related publications: Calderan et al., Artificial Organs, 2016; Mao et al., CVET, 2016; Caballero et al., CVET, 2016; Mao et al., PloS one, 2017; Eric et al., Artificial Organs, 2018
Particle/cell separation in microfluidics
Microfluidics deal with the behavior and manipulation of fluids in channels with dimensions of sub-millimeter scale. Sorting and separation of particles are key elements in many microfluidic processes. Previous studies focusing on spherical particles and droplets may not be applicable to the manipulation of compliant biological cells and synthetic capsules in microfluidic devices. First, we developed a numerical model combined the lattice Boltzmann method (LBM) for fluids and the mass-spring model for solids to study the dynamics of deformable capsules in microchannels. Inspired by this fundamental study, my collaboration with the Sulchek BioMEMS Lab turned out a new design of a microfluidic device for continuous, label-free cancer cell separation and detection by mechanical stiffness. We investigated the underlying mechanism of cell separation through numerical simulations, which were in good agreement with experimental results. This sorting method would greatly complement existing separation techniques, which are critical for detecting diseases such as cancers and sickle-cell anemia.
soft cell
stiff cell
We use computational modeling to design a hydrodynamic method for high-throughput separation of solid microparticles by size in microchannels. The rapid and high-resolution separation occurs due to a combination of two hydrodynamic effects: cross-stream inertial migration of particles and circulatory fluid flows created by periodic diagonal ridges protruding from opposite channel walls. This new continuous separation method operates in a wide range of Reynolds numbers, is insensitive to the magnitude of channel flow rate, and features simple design that can be readily integrated into microfluidic devices for massive sample analysis.
In nature, biological and synthetic particles are normally non-spherical. Therefore, I extended my work to the dynamics of spheroid particles in a flow. Although the rotation of spheroids in shear flows has been widely studied, a comprehensive understanding of the combined effect of fluid and particle inertia on the orientation of spheroids with different aspect ratios is yet to be established. Our numerical study filled the gap and systematically investigated the complex dynamics of spheroids in a shear flow, which deviates from Jeffery’s orbits due to the inertial effect. The results and techniques used in this study can be applied for designing microfluidic devices for separation of non-spherical particles. Indeed, collaborated with the Dr. Di Carlo's Lab at UCLA, we explored that this high-throughput shape-based separation can be applied to a large range of particle sized and types, including artificially made 3-µm particles as well as bioparticles such as yeast
Micromixing
Micromixing is a key technology to fields such as pharmaceutical industry, analytical chemistry, biochemical analysis, and high-throughput synthesis since it reduces the quantity of agents involved in the chemical and/or biochemical processes. My research in this field expanded the understanding of rapid mixing and facilitated the design of two active micromixers. One of the design is to utilize pulsating square waves introduced at the entrances of a simple T-type mixer. This process significantly increases the interface area of fluids allowing them to reach a uniform mixing rapidly. Key parameters, such as the Reynolds number, the Strouhal number, and the amplitude of pulsatile wave and their compounding effect on the mixing efficiency were thoroughly investigated. Collaborated with Dr. Peter Hesketh at Georgia Tech, we devised a novel mixing method by the manipulation of magnetic beads. Previous electromagnetic micromixers are limited to the manipulation of a small number of magnetic beads due to Joule heating. Our device overcame this limitation by using soft magnetic patterns on the microchannel wall to control the motion of a large amount of super-paramagnetic beads. Through CFD and magnetic field modeling, I deduced the best mixing parameters for achieving the most effective mixing.
Links to Related publications: Mao et al., Int. J. Heat Mass Transfer, 2009; Owen et al., Micromachines, 2013
Thermocapillary flows
Thermocapillary flow or Marangoni convection is the mass transfer along an interface between two fluids due to surface tension gradient induced by the temperature difference. For open microfluidic devices, free-surface flows can be actuated by thermocapillary convection. We performed CFD simulations (the volume-of-fluid method) and the long-wave theory (collaborated with Dr. Alexander Oron at Technion) to study the thermocapillary flow arising in a thin liquid film on a non-uniform heated solid substrate. An efficient fluid pumping mechanism was discovered. In a similar scenario, when the Marangoni number exceeds the threshold value, the film breaks into a series of drops with minuscule fluid bridges connecting each of them. By increasing the wave frequency, the bridges thicken and allow fluid to transfer between the drops. Both of these studies revealed new free-surface flow techniques in microfluidics and provided engineers with more tools in the design.
Links to Related publications: Mao et al., Phys. Fluids, 2013; Frumkin et al., Phys. Fluids, 2014
Aerodynamics of eyelashes
While it is known that eyelashes serve as protection and prevent eye infections, the correct physical explanation has been unknown. Collaborated with the Dr. Hu’s Biolocomotion Lab at Georgia Tech, we performed a study on the aerodynamic characteristic of eyelashes using physical experiments in a wind tunnel and numerical simulations. We found that eyelashes diverted airflows, thereby acting as a passive dust controlling system for eyes. Most mammal eyelashes are the optimum length since any longer eyelashes would funnel particles into eyes. In a separate study, I applied similar techniques to the ocular hairs found on insects. Just like mammal eyelashes, insect ocular hairs were proven to have an optimal ratio, with hair length equaling their spacing. This study revealed that an array of hairs reduces surface airflow by 90%, effectively creating a shield of stagnant air for a flying insect. These studies not only elucidated the long mysterious function of eyelashes, but also shed light on a new perspective of the dust cleaning system.
streamlines without eyelashes
streamlines with long eyelashes
Links to Related publications: Amador et al., J R Soc Interface, 2015; Amador et al., Eur. Phys. J, 2015