Session Y01: Biological Fluid Dynamics: Medical Devices (11:30am - 12:15pm CST)

Mathematical model of a valve-controlled, gravity driven bioreactor for platelet production

Hospitals sometimes experience shortages of donor blood platelet supplies, motivating research into~\textit{in vitro}~production of platelets. We model a novel platelet bioreactor described in Shepherd et al.$^{\mathrm{1}}$~The bioreactor consists of an upper channel, a lower channel, and a cell-seeded porous collagen scaffold situated between the two. Flow is driven by gravity, and controlled by valves on the four inlets and outlets. The bioreactor is long relative to its width, a feature which we exploit to derive a lubrication reduction of unsteady Stokes flow coupled to Darcy. As the shear stress experienced by cells influences platelet production, we use our model to quantify the effect of varying pressure head and valve dynamics on shear stress. ~ 1:~Shepherd, J.H., Howard, D., Waller, A.K., Foster, H.R., Mueller, A., Moreau, T., Evans, A.L., Arumugam, M., Chalon, G.B., Vriend, E. and Davidenko, N., 2018. Structurally graduated collagen scaffolds applied to the ex vivo generation of platelets from human pluripotent stem cell-derived megakaryocytes: enhancing production and purity.~\textit{Biomaterials},~\textit{182}, pp.135-144.   

Dynamics of droplets on COVID-19 transmission via a soft wireless device and Particle Tracking Velocimetry

Fundamental understanding of droplet dynamics generated by various breathing activities and testing strategies for COVID-19 with widespread availability become critical components for containing the pandemic and preventing other droplet transmission diseases. To directly address needs in COVID-19 monitoring and investigation of droplet dynamics, simultaneous measurements are performed via a thin, flexible, wireless, wearable sensor that consists of a wide-bandwidth inertial measurement unit as well as a precision temperature sensing unit, and Particle Tracking Velocimetry (PTV). The flexible sensor mounts on the suprasternal notch for accurate recordings of the respiratory activity, and offers the advantage of non-invasive and continuous monitoring. PTV allows for the quantification of the size distribution of generated droplets and Lagrangian dynamics of individual droplet trajectories. We particularly focused on the frequency, intensity, and duration of several respiratory activities, such as coughing, talking, and laughing. The work provides a framework for ongoing clinical studies on actual patients at the Northwestern Memorial Hospital in Chicago and a crucial understanding of unusual infectious individuals, the so-called ``Superspreaders''.   

Shape optimisation for faster washout in recirculating flows

How to design an optimal biomedical device to minimise trapping of undesirable biological solutes/debris is a pertinent but complex question. We address this challenge, deriving particular motivation from \textit{ureteroscopy}, a minimally invasive surgical procedure for the removal of kidney stones by irrigating dust-like stone fragments with a saline solution. \\ We represent the renal pelvis as a 2D cavity and model fluid flow with the steady, incompressible Navier--Stokes equations. Within this modelling framework, the presence of vortices -- which arise as a result of flow symmetry breaking -- has previously been linked to long washout times of kidney stone dust; modelled via advection and diffusion of a passive tracer. \\ For a given flow field $\mathbf{u}$, vortices are characterised by regions where $\det\nabla\mathbf{u} > 0$. Thus, integrating a smooth form of $\max(0,\det\nabla\mathbf{u})$ over the domain provides an objective to minimise recirculation zones. We employ adjoint-based shape optimisation to identify ureteroscope tip geometries that reduce this objective. We show that a reduction in the vortex objective correlates with a reduction in washout time, and hence determine tip shapes which result in reduced washout times.   

Multiscale Mathematical Models for Tendon Tissue Engineering

Tendon tissue engineering aims to grow functional tendon in vitro. In bioreactor chambers, cells growing on a solid scaffold are fed with nutrient-rich media and stimulated by mechanical loads. The Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences is developing a Humanoid Robotic Bioreactor, where cells grow on a flexible fibrous scaffold actuated by a robotic shoulder. Tendon cells modulate their behaviour in response to shear stresses - experimentally, it is desirable to design robotic loading regimes that mimic physiological loads. The shear stresses are generated by flowing cell media; this flow induces deformation of the scaffold which in turn modulates the flow. Here, we capture this fluid-structure interaction using a homogenised model of fluid flow and scaffold deformation in a simplified bioreactor geometry. The homogenised model admits analytical solutions for a broad class of forces representing robotic loading. Given the solution to the microscale problem, we can determine microscale shear stresses at any point in the domain. In this presentation, we will outline the model derivation and discuss the experimental implications of model predictions.   

Bioprosthetic Aortic Valve Diameter and Thickness Are Directly Related to Leaflet Fluttering: Results from a Combined Experimental and Computational Modeling Study

Bioprosthetic heart valves (BHVs) are commonly used in surgical and percutaneous valve replacement, and surgical valves have been shown to have a time to reintervention of 10--15 years. Further, smaller-diameter surgical BHVs generally have higher-rates of prosthesis-patient mismatch than larger valves. Bioprosthetic aortic valves can flutter in systole, and fluttering is associated with fatigue and failure in natural and manufactured structures. The determinants of flutter in BHVs have not been well characterized, however, despite their potential to impact BHV durability. We use an experimental pulse duplicator platform and a computational model of this system to study the role of device geometry on BHV dynamics. We systematically characterize the impact of BHV diameter and leaflet thickness on fluttering dynamics. Ultimately, understanding the effects of device geometry on leaflet kinematics may lead to more durable valve replacements.   

Simulation of a Vacuum Helmet to Contain Pathogen-Bearing Droplets in Dental, Otolaryngologic, and Ophthalmologic Outpatient Interventions

Clinic encounters of dentists, otolaryngologists, and ophthalmologists inherently expose these specialists to an enhanced risk of SARS-CoV-2 infection, thus threatening them, their patients, and their practices. In this study, we propose and simulate a vacuum helmet used on patients to minimize transmission risk by containing droplets created through coughing. The helmet has an accessible face opening and a connected suction device to prevent droplets from exiting thought the face opening and contaminating the environment or clinical practitioners. We used CFD in conjunction with point-particle tracking to simulate droplet trajectories when a patient coughs while using this device. A wide range of particle diameters and unsteady flow conditions are considered in the simulations. The effectiveness of the proposed design in containing droplets is demonstrated.   

Noninvasive Central Blood Pressure Measurement Methodology Inspired From Tonometry and Oscillometric Principles.

Why does blood pressure measurement location influence patient prognosis? Blood pressure has a spatial and temporal dependence in the cardiovascular system. When forward propagating pressure waves reach reflections sites, they reflect backwards with patient specific intensity and shape. Superposition of forward and backward pressure waves is location and time dependent and directly influences blood pressure. In cardiology, blood pressure measurements are used as prognostic markers for heart health. Thus, the ideal outcome is determining pressure in the ascending aorta: central blood pressure. Yet, the clinical gold standard still assesses blood pressure in peripheral arteries. Clinicians have been using this measurement as a surrogate for central blood pressure, often obtaining limited cardiovascular information that can lead to incorrect clinical decisions. Central blood pressure measurement is seldom obtained due to measurement invasiveness and complexity. To address these limitations, we are proposing a noninvasive spatially dependent blood pressure measurement at the carotid artery. Our application combines tonometry and oscillometric sphygmomanometer principles with pulse wave analysis for patient specific carotid pressure measurements.   

Design, build and test of an in-house made ventilator system

The Covid-19 outbreak presented a serious challenge to the world healthcare. Its rapid spread overwhelmed the hospitals' capacity to efficiently contend with the increasing number of patients requiring immediate respiratory assistance. As the ventilators are relatively expensive (typically ranging from {\$}5,000 to {\$}50,000), and in case the healthcare capacity is outnumbered, the design of a cost-effective and a quick-home-made ventilator becomes crucial. This project represents an answer to this emergency. It is about the design, build and test of a ventilator which is affordable at low cost, easy to be operated, while meeting the essential requirements set by the Food and Drug Administration. The ventilator is composed of a valve to regulate and monitor the air pressure, a timer that controls a solenoid valve to provide pulsating air flow, a humidifier to add moisture to the air flow and a PEEP (Positive End of Expiratory Pressure) valve to maintain the pressure in human lung. An air compressor or a plant air serves the source for the air supply. A lung simulator is used to test the performance of the ventilator at different pulmonary compliance settings. The parameters including the air pressure, the inspiration time and the PEEP are fully controllable.   

Groundbreaking Self-Breathing Ventilator Investigation

With the rise in global devastation created by the COVID-19 pandemic, the world needs a cheap, simple, and disposable ventilator containing no moving parts. We computationally explore the intricacies of the world's smallest ventilator, the \textbf{HOPE inVent}. When connected to a modest motive gas source, this 3-D printed device will self-pulse and ventilate an unconscious patient or support the breathing of a conscious patient. Pulsations occur because of the well-known Coanda effect coupled with acoustic interactions and turbulent instabilities at various scales. Its efficacy is demonstrated, and the influence of several important geometric parameters is revealed.   

Transient numerical modelling of impact driven needle-free jet injectors

Instead of using a thin metal rod i.e., needle to puncture the skin, intradermal needle-free jet injectors (NFJI) use the liquid drug itself to pass the skin barrier. The impact driven NFJIs generate a high-speed liquid jet using an actuation sources such as compressed spring, pressurized air, or explosive charge. There are two phases of jet injection i.e., initial high-pressure impulse phase and constant jet speed injection phase. The high-pressure (10$^{\mathrm{6}}$ Pa) impulse can adversely affect needle-free jet injector components such as plastic cartridges/nozzles and reduce their lifespan. This high-pressure impulse can also cause cavitation and damage the drug sample or device slippage from the targeted delivery area. Transient simulations are performed to study the role of nozzle geometry and fluid rheology on system properties such as jet exit velocity, peak stagnation pressure. We observe that the peak stagnation pressure increases significantly with increasing fluid viscosity. By studying a range of nozzle geometries such as multi-tier tapers and asymmetric sigmoid contractions, we see that the power of actuation sources and nozzle geometry can be tailored to deliver drugs with different fluid viscosities in the intra-dermal region of skin.   

Simulating inhaled transport through bio-inspired pathways in mask filters

Without a COVID-19 vaccine or an antiviral therapeutic, face coverings will become a norm in our lives. Current masks/respirators were not designed for SARS-CoV-2. Their shielding ability from inhaling virus-laden droplets is accompanied by a significant loss in quality-of-life from low breathability. In this scenario, we took cues from the nasal airway shapes in animals with highly enhanced olfactory organs whose tortuous geometries, owing to re-circulating flow patterns therein, can efficiently trap particulates. We consider 4 different bio-inspired designs to serve as air-transmission passages in mask filters and have quantified the droplet capturing efficiency along the airway walls. At tested breathing rates of 15, 30, 55, and 85 L/min, the designs generally capture all droplets bigger than 5 $\mu$ and more than 95 percent of the droplets sized at 5 $\mu$. Capturing rates drop to 60-80 percent for 4-$\mu$ droplets, 15-30 percent for 3-$\mu$ droplets, and beyond that, the capturing efficiency decays exponentially. The simulations use steady-state laminar-viscous models for gentle breathing; RANS-based SST k-$\omega$ and LES schemes to track turbulent transport at higher inhalation rates. Finally, we extract the inlet-to-outlet pressure gradients to quantify for breathability.   

CO-AXL: Enhancing the injectability of high concentration drug formulations using co-axial lubrication

Subcutaneous injection of concentrated drug formulations via commercial syringes is currently limited by the high viscosity of such formulations. Current approaches to solve this problem face challenges such as high cost and manufacturing complexity. In this work, we present CO-AXL -- a double-barreled syringe that dramatically enhances the range of manually injectable viscosities compared to conventional syringes without a significant increase in price. The CO-AXL syringe utilizes a core annular flow, where the convection of the highly viscous formulation is facilitated by co-axial lubrication by a less viscous fluid, to reduce the hydrodynamic resistance of fluid flow in the needle. A phase diagram to achieve optimal lubrication is established, and the role of buoyancy based eccentricity in regulating the nominal pressure reduction is also examined. Up to a 7x reduction in injection force is experimentally achieved, demonstrating the promise of the technique to enhance the injectability of high concentration formulations and to create a pathway toward better patient health and lower treatment costs.   

Input-Output Analysis of Fluid-Structure Interaction to Optimize Stone Breakage in Lithotripsy

Burst-wave lithotripsy (BWL) is a non-invasive treatment of kidney stones using short pulses of focused ultrasound generated by a multi-element array medical transducer. In this work, we apply input-output analysis to optimize the design parameters of the transducer to optimize stone breakage. The frequency-domain analysis is based on a linear fluid-structure coupled system that maps the acoustic forcing from individual elements to the stress and strain in the stone. We maximize a cost function that represents the strain energy in the stone, and determine the forcing that gives rise to the maximum amplification. Specifically, the optimal forcing and the corresponding response are found through the singular value decomposition of the resolvent operator of the system. The result shows that under the same input energy, altering the amplitude and the phase of elements along the array can lead to an increase of strain energy (by 2-3 times in certain cases) compared to a uniform distribution. This indicates that the stone fragmentation could be accelerated or performed at a lower and hence safer level of energy. Results for optimizing other design parameters, including array geometry, focal distance and aperture, will also be presented.   

Vortex traps to capture particles with reduced pressure loss in respiratory masks.

With the rapid spread of the Coronavirus Disease 2019 (COVID-19) worldwide, highly-protective respirator masks play an important role in mitigating the likelihood of contagion and spreading. A central challenge on the design of effective masks is the capture of sufficiently small droplets with reduced pressure loss penalty. Using vortex traps with convoluted geometries or tortuous passages (passive strategy) and thermophoresis action (active strategy), we designed a series of mask filters that aim to enhance particle trapping requiring a relatively low-pressure gradient. Here, we will describe laboratory experiments on the passive strategy with selected filter geometries at various Reynolds and Stokes numbers. Three-dimensional Particle tracking velocimetry was used to characterize the Lagrangian dynamics of a large number of particles with different sizes in the vicinity of the filters, which was linked to the pressure gradient across the tortuous passages. We will also point out results from simulations and fundamental insights from the characterization of animal nasal cavities.   

Assessing Hemodynamics in the Ascending Aorta due to Surgical Anastomosis and Flow Modulation of Left Ventricular Assist Device.

A Left Ventricular Assist Device (LVAD) is a surgically implantable blood pump that supports the circulatory function of the left ventricle. LVADs are widely used as bridge-to-transplant as well as destination therapy for advanced heart failure patients. However, LVAD therapy is commonly associated with complications such as pump thrombosis, ischemic stroke, and gastrointestinal bleeding. These complications are intimately related to the altered state of hemodynamics induced by LVAD pump flow and outflow cannula anastomosis. Our objective in this study is to quantify the flow features in the vicinity of the anastomosis by systematic variation of LVAD cannula angle and pump flow pulsatile modulation using 3D computational hemodynamics simulations. We use patient computed tomography images to create an aorta model and virtually implant an LVAD outflow cannula in 9 different orientations. A constant flow, and low and high levels of pulsatile flow modulation are considered for each model. We identify variations in flow velocity, normalized helicity and wall shear stress patterns as a function of mentioned key parameters and compare our observations to flow in normal aorta without LVAD support. Insights from these observations can enable improved LVAD therapy decision making.   

Interchangeable filter characterization for COVID-19 protection

We have proposed a novel interchangeable filter for masks to curb the spread of respiratory viruses. The multi-layer filter holds novelty in its layers: layer A – hydrophobic & lipophobic layer (using nano-engineered, halogen-free, super omni-phobic coatings), layer B – DLC coated copper layer, and layer C – which is a non-woven layer. The varying fiber arrangement of layer C along with the droplet resistant layer A, and pathogen fighting layer B, makes it an efficient filter in comparison to N-95 and surgical masks, as suggested from our preliminary experimental results. We have characterized the filter through experiments and simulations, where the experiments include flow visualization of the saliva particle flow, and measurements using optical particle counter in order to determine the qualitative and quantitative efficiency of the filter. We measured the pressure drop vs velocity across the filter, used for determining the viscous and inertia resistance coefficients, crucial in verification of the simulations and pressure drop across filter. We used ANSYS FLUENT discrete phase model to simulate the flow through the filter and modeled filter as porous media. This helps us shed light on how the proposed filter can prevent and inactivate the nanoscale pathogens.   

Pufferfish: Developing a rapidly scalable full-feature ventilator for COVID-19 patients with ARDS

We describe a rapidly scalable open-source full-feature ICU ventilator designed for COVID-19 patients with ARDS. Pufferfish was designed in a consortium effort with multiple universities and industrial partners to address ventilator shortages, including accounting for uncertainties in the supply chains of parts commonly used in traditional ventilators to enable distributed manufacturing. Pufferfish supports all common modes of ventilation including both volume and pressure control modes, with component cost of the system to be around $500. We will discuss control strategies for pneumatics circuit utilized. More broadly, we will discuss the context of distributed development of medical devices rapidly in regulatory framework. See www.pez-globo.org for details.   

Modified Full-Face Snorkel Masks as Reusable Personal Protective Equipment for Hospital Personnel

In the spring of 2020, an international coalition created a reusable PPE solution for healthcare workers, in response to the global supply chain collapse of N95 respirators triggered by the SARS-CoV-2 pandemic. The device, "Pneumask", consists of a modified full-face snorkel mask, adapted to interface with FDA or NIOSH-rated inline respiratory filters. This project involved the characterization of fluid flow through the device with industry-standard CFD tools (STAR-CCM+) to evaluate CO2 species transport, one-way valve performance, fit testing, filter characterization, and the clinical evaluation of the device. On each of these fronts, our conclusions on the performance of Pneumask were cautiously optimistic, for use as a stop-gap alternative to disposable N95 respirators. The design was distributed at scale, with thousands of units deployed domestically, and tens of thousands in use internationally. This deeply collaborative team project demonstrates an applied example of how our modern understanding of fluid mechanics can be used to save lives in times of human crisis.