Session Q14: Biological Fluid Dynamics: Medical Devices I

Breath sensors that are self-powered by design

Piezoelectric materials are widely used to generate electric charge from mechanical deformation or vice versa. These strategies are increasingly common in implantable medical devices, where sensing must be done on small scales. In the case of a flow rate sensor, a sensor's energy harvesting rate could be mapped to that flow rate, making it "Self-Powered by Design (SPD)". Prior fluids-based SPD work has focused on turbulence-driven resonance and has been largely empirical. Here we explore sub-resonance SPD sensing via a case study of human breathing. We present a model of self-powered piezoelectric sensing/harvesting  and validate that model against experimental results. Our work offers a form of SPD sensing that scales down to micro- or nano-scales, where flows are locally laminar and wake-driven resonance is not an option, and offers a model-based roadmap for future SPD sensing solutions. We also use the model to theorize a new form of SPD sensing that can detect broadband flow information.   

Optimal Control of Phased-Array Ultrasound Transducer for Lithotripsy Using Input-Output Analysis

Burst-wave lithotripsy is a non-invasive treatment of kidney stones using short pulses of focused ultrasound. In this talk, we present the use of input-output analysis (a frequency domain approach) to optimize the design and control of a multi-element array transducer to optimize stone breakage. The analysis is based on a linear fluid-structure coupled system that maps the acoustic forcing from individual elements to the stress in a stone of assumed shape, size, and composition. We determine the optimal frequency and optimal distribution of the phase and amplitude across the aperture by maximizing a cost function that represents the strain energy in stone. The optimal parameters are obtained by applying a state-of-the-art, randomized singular value decomposition to the discrete linear operator. The results show that under the same input energy, carefully controlling the relative phase and amplitude between elements can increase strain energy (by 2-3 times in certain cases) compared to a uniform distribution. This suggests that stone fragmentation can be accelerated or performed with lower energy for safer treatment. The improvement is validated by combining high-fidelity simulations with high-speed camera images of crack formation in model stones from in-vitro experiments.   

Not Participating

Hemodialyzers are designed to replicate the function of the kidneys and filter a patient’s blood through a semi-permeable membrane. The clearance of unwanted chemical species, such as urea, depends on the membrane properties and the dialysate and blood flow rates. Here, we measured an Optiflux® F180 dialyzer (Fresenius Medical Care) using a Stemi 2000 Zeiss stereomicroscope and high precision calipers and found that it had approximately 12,600 hollow fibers, a dialyzer inner diameter of 49.53 mm, a hollow fiber inner diameter of 185 μm, a membrane thickness of 36 μm, and a dialyzer length of approximately 266 mm. The geometric complexity of the device precludes performing fully three-dimensional multiphysics simulations involving fluid mechanics and transport of species. Following Karniadakis et al. (Nature Reviews Physics, 2021), we used a physics-informed neural network to model the urea clearance in the model hemodialyzer. We enforced the continuity equation, the Navier-stokes equations and the advection-diffusion equation by training the network on additional information obtained with less computationally expensive results, including those obtained by reducing the number of hollow fibers, which were obtained from finite element analysis software. The neural network model successfully reproduced known clinical urea clearance rates and thus may serve as a useful tool for designing hemodialysis membranes and optimizing flow conditions for medical conditions such as acute kidney injury (AKI).    

Multi-layered and foam-gel composites as a Model for Needle Free Jet Injections

Needle-free jet injections is a growing area of research as an alternative to needle-and-syringe inoculations. To further study this area, it is crucial to understand the fluid dispersion inside the targeted tissue. Due to the cost and limited availability of skin a transparent in vitro model made to represent tissue layers is needed. Previous studies have used single-layer gel substrates with mechanical properties reminiscent of tissue layers. However, typical drug delivery target tissues (intradermal, subcutaneous, muscle) are each composed of a complex system of fibers and cells with differing mechanical properties. In this study we construct a multi-layered hydrogel with various concentrations to match the mechanical properties of each layer of tissue; This study explores both the transient dynamics and final shape of the fluid bolus from jet injection in such substrates. The results of our research involving multi-layered hydrogel are in better agreement with ex vivo dispersion patterns compared to the results obtained for single-layer gels. We also consider a novel substrate using gel-soaked sponges as a proxy for subcutaneous tissue.   

A 3D-printed microneedle array and reservoir for testing transdermal drug delivery

Currently available approaches for delivering pharmaceuticals and biologicals include oral administration, syringe injection, and delivery through a powered pump or patch. Oral administration is a very common approach that is used to deliver approximately 60% of small-molecule drugs, yet it is very difficult to use for the delivery of large-molecule substances due to their poor ability to cross the walls of the gastrointestinal (GI) tract intact. Syringe injection is likely to cause injection site reaction (pain), is inconvenient, and can be problematic because of the non-continuous nature of the delivery. And delivery with a pump, though continuous, requires a battery that is bulky and interferes with daily activity. Therefore, there is a need for transdermal patch drug delivery solutions that use microneedle arrays in order to alleviate the problems outlined above. Our objective for this study is to test transdermal flow characteristics of a custom-built, 3D-printed microneedle array enclosed in a reservoir using porcine skin samples ex vivo. During testing, the 3D-printed apparatus will be connected to the flow channel of a pre-fabricated microfluidic drug delivery device. A number of supracutaneous flow rates will be tested, while flow characteristics including subcutaneous flow rates and hydraulic resistances will be determined. We expect that our apparatus will be able to deliver fluid across the skin continuously and efficiently, and that subcutaneous flow characteristics will not differ significantly from the supracutaneous flow. As an integral component of a patch used for the delivery of drugs such as insulin in humans, the 3D-printed apparatus will be tested for flow characteristics in healthy human subjects and computationally optimized as the next future steps.    

Effects of elasticity on tissue growth in a tissue-engineering scaffold pore

Scaffolds engineered for use in tissue regeneration consist of multiple pores which are lined with cells, through which nutrient-rich culture medium flows. Nutrient solution circulates throughout the scaffold pores, promoting cellular proliferation. The proliferation process depends on several factors such as; scaffold geometry, the nutrient solution flow rate, the shear stress, and the elastic properties of the scaffold material. These factors greatly affect tissue growth rate. Recent studies focus on the first three factors, while in this work, we focus on the cellular growth rate in elastic scaffolds under constant flux of nutrients. As cells grow, the pore radius decreases, therefore, in order to sustain the nutrient flux, the inlet applied pressure at the top of the scaffold pore should be increased. This results in expansion of the elastic scaffold pore, which in turn influences the growth rate of cells. Under elastic conditions, the pore deformation allows further tissue growth beyond that of inelastic conditions. In this paper, our objectives are as follows: (i) develop a mathematical model for cell proliferation describing fluid dynamics, scaffold elasticity, and tissue growth; (ii) solve the models and then simulate the tissue proliferation process. The simulation can emulate real-life cell growth in a tissue engineering pore and offer a solution that reduces the numerical burdens. Our algorithm is demonstrated to be in agreement with experimental observations from literature.    

A better way to spray? – a model-based optimization of nasal spray use protocols

Drug delivery for viral infections, such as SARS-CoV-2, can be enhanced significantly by targeting the nasopharynx, which is the dominant initial infection site in the upper airway, for example by nasal sprays. However, under the standard protocol ("current use" or CU), the nozzle enters the nose almost vertically, resulting in suboptimal deposition of drug droplets at the nasopharynx. Using computational fluid dynamics (CFD) simulations in four anatomic nasal geometries, we propose an "improved use" (IU) protocol. It entails pointing the spray bottle at a shallower angle (almost horizontally), aiming slightly towards the cheeks. We have simulated the performance of this protocol for conically injected spray droplet sizes of 1–24 µm at two breathing rates: 15, 30 L/min. The lower flowrate is for resting breathing and follows a viscous-laminar model; the higher rate is turbulent and is tracked via Large Eddy Simulation. Experimentally-validated CFD results show that targeted delivery via IU outperforms CU by over 2 orders of magnitude, for both flowrates. Improved delivery by IU is robust to small changes in spray direction, underlining the practical utility of this simple change in administration protocol.   

Lubrication model of a valve-controlled, gravity-driven bioreactor

Hospitals sometimes experience shortages of donor blood platelet supplies, motivating research into in vitro production of platelets. We model a novel platelet bioreactor described in Shepherd et al. [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 Navier-Stokes flow coupled to Darcy. Models for two cases are considered: small amplitude valve oscillations, and order one amplitude valve oscillations. The former model is a systematic reduction; the latter incorporates a phenomenological approximation for the cross-sectional flow profile. As the shear stress experienced by cells influences platelet production, we use our model to quantify the effect of 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., Biomaterials, 182, pp.135-144. (2018)   

A novel capillary-based flow cell for flow cytometry

Flow cytometry is an analytical technique used in biomedical diagnostics, that measures properties of cells, micro-organisms and particles. Laser light is scattered from particles focused in a flowcell and collected by light sensors (photodiodes) where the intensity of the scattered light is a function of the scattering angle, refractive index of the particle and surrounding medium, wavelength of light and size and the shape of the particle. One of the critical parts of the cytometer is the flow cell where the particle stream is constrained into a tight region using hydrodynamic focusing. The conventional flow cells use thick quartz flow cells, they are expensive, therefore not suitable for instruments targeted for resource-constrained settings. We propose a low-cost sheath flow assembly design made of micro-tight ETFE adapters and an assembly of capillary tubes for passage of focused flow of particles. The entire flow cell assembly is a simplified version of a sheath flow cuvette design able to focus and accelerate a stream of particles in a narrow region probed by the incident laser. We show excellent agreement between size distribution obtained via direct imaging and those obtained from light scattering. With minor modifications, the device may be used for disease detection.