Computational simulation of the flow dynamic field in a porous ureteric stent

Ureteric stents are employed clinically to manage urinary obstructions or other pathological conditions. Stents made of porous and biodegradable materials have gained increasing interest, because of their excellent biocompatibility and the potential for overcoming the so-called ‘forgotten stent syndrome’. However, there is very limited characterisation of their flow dynamic performance. In this study, a CFD model of the occluded and unoccluded urinary tract was developed to investigate the urinary flow dynamics in the presence of a porous ureteric stent. With increasing the permeability of the porous material (i.e., from 10−18 to 10−10 m2) both the total mass flow rate through the ureter and the average fluid velocity within the stent increased. In the unoccluded ureter, the total mass flow rate increased of 7.7% when a porous stent with permeability of 10−10 m2 was employed instead of an unporous stent. Drainage performance further improved in the presence of a ureteral occlusion, with the porous stent resulting in 10.2% greater mass flow rate compared to the unporous stent. Findings from this study provide fundamental insights into the flow performance of porous ureteric stents, with potential utility in the development pipeline of these medical devices. Graphical abstrac

Rapid and mask-less laser-processing technique for the fabrication of microstructures in polydimethylsiloxane

We report a rapid laser-based method for structuring polydimethylsiloxane (PDMS) on the micron-scale. This mask-less method uses a digital multi-mirror device as a spatial light modulator to produce a given spatial intensity pattern to create arbitrarily shaped structures via either ablation or multi-photon photo-polymerisation in a master substrate, which is subsequently used to cast the complementary patterns in PDMS. This patterned PDMS mould was then used for micro-contact printing of ink and biological molecules

Flow Dynamics in Stented Ureter

Urinary flow is governed by the principles of fluid mechanics. Urodynamic studies have revealed the fundamental kinematics and dynamics of urinary flow in various physiological and pathological conditions, which are cornerstones for future development of diagnostic knowledge and innovative devices. There are three primary approaches to study the fluid mechanical characteristics of urinary flow: reduced order, computational, and experimental methods. Reduced-order methods exploit the disparate length scales inherent in the system to reveal the key dominant physics. Computational models can simulate fully three-dimensional, time-dependent flows in physiologically-inspired anatomical domains. Finally, experimental models provide an excellent counterpart to reduced and computational models by providing physical tests under various physiological and pathological conditions. While the interdisciplinary approaches to date have provided a wealth of insight into the fluid mechanical properties of the stented ureter, the next challenge is to develop new theoretical, computational and experimental models to capture the complex interplay between the fluid dynamics in stented ureters and biofilm/encrustation growth. Such studies will (1) enable identification of clinically relevant scenarios to improve patients’ treatment, and (2) provide physical guidelines for next-generation stent design

Early biofilm and streamer formation is mediated by wall shear stress and surface wettability: A multifactorial microfluidic study

Biofilms are intricate communities of microorganisms encapsulated within a self-produced matrix of extra-polymeric substances (EPS), creating complex three-dimensional structures allowing for liquid and nutrient transport through them. These aggregations offer constituent microorganisms enhanced protection from environmental stimuli—like fluid flow—and are also associated with higher resistance to antimicrobial compounds, providing a persistent cause of concern in numerous sectors like the marine (biofouling and aquaculture), medical (infections and antimicrobial resistance), dentistry (plaque on teeth), food safety, as well as causing energy loss and corrosion. Recent studies have demonstrated that biofilms interact with microplastics, often influencing their pathway to higher trophic levels. Previous research has shown that initial bacterial attachment is affected by surface properties. Using a microfluidic flow cell, we have investigated the relationship between both wall shear stress (τw) and surface properties (surface wettability) upon biofilm formation of two species (Cobetia marina and Pseudomonas aeruginosa). We investigated biofilm development on low-density polyethylene (LDPE) membranes, Permanox® slides, and glass slides, using nucleic acid staining and end-point confocal laser scanning microscopy. The results show that flow conditions affect biomass, maximum thickness, and surface area of biofilms, with higher τw (5.6 Pa) resulting in thinner biofilms than lower τw (0.2 Pa). In addition, we observed differences in biofilm development across the surfaces tested, with LDPE typically demonstrating more overall biofilm in comparison to Permanox® and glass. Moreover, we demonstrate the formation of biofilm streamers under laminar flow conditions within straight micro-channels

The accumulation of particles in ureteric stents is mediated by flow dynamics: Full-scale computational and experimental modeling of the occluded and unoccluded ureter

Ureteric stents are clinically deployed to restore urinary drainage in the presence of ureteric occlusions. They consist of a hollow tube with multiple side-holes that enhance urinary drainage. The stent surface is often subject to encrustation (induced by crystals-forming bacteria such as Proteus mirabilis) or particle accumulation, which may compromise stent's drainage performance. Limited research has, however, been conducted to evaluate the relationship between flow dynamics and accumulation of crystals in stents. Here, we employed a full-scale architecture of the urinary system to computationally investigate the flow performance of a ureteric stent and experimentally determine the level of particle accumulation over the stent surface. Particular attention was given to side-holes, as they play a pivotal role in enhancing urinary drainage. Results demonstrated that there exists an inverse correlation between wall shear stress (WSS) and crystal accumulation at side-holes. Specifically, side-holes with greater WSS levels were those characterized by inter-compartmental fluid exchange between the stent and ureter. These “active” side-holes were located either nearby ureteric obstructions or at regions characterized by a physiological constriction of the ureter. Results also revealed that the majority of side-holes (>60%) suffer from low WSS levels and are, thus, prone to crystals accumulation. Moreover, side-holes located toward the proximal region of the ureter presented lower WSS levels compared to more distal ones, thus suffering from greater particle accumulation. Overall, findings corroborate the role of WSS in modulating the localization and extent of particle accumulation in ureteric stent

Nanoparticle-enhanced chemiluminescence in micro-flow injection analysis

Chemiluminescence (CL) detection for biomedical analysis has the principal advantage that no optical source is required so that instrumentation is simple and background radiation is minimised, resulting in high sensitivity. CL has been exploited in a wide range of chemical and biochemical measurements such as enzyme-linked immunoassays (ELISA), DNA sequencing, and for the analysis of biomedical, food and environmental samples [1]. CL is ideally suited to microfluidic flow-injection analysis (µFIA), due to the precise temporal and space control of sample/reagent aliquots [2]. However, while CL is a sensitive technique, the ultrasmall volumes employed in µFIA lead to low emitted power, so that signal enhancement methods are required to achieve suitable detection limits. Gold and silver nanoparticles (GNPs and SNPs) may provide enhancement of optical signals due to collective oscillation of conduction electrons excited by the electromagnetic field or due to catalysis [3,4]. In this study, CL of luminol was investigated in a microflow chip with a serpentine channel of width 600 µm, depth 75 µm and length 150 mm formed in polydimethylsiloxane (PDMS) by moulding over a 3D printed master

Mechanisms of encrustation within ureteral stents

Ureteric obstructions due to intrinsic or extrinsic causes (e.g., stones, tumours, and fibrosis) can impair urine flow, resulting in pain, urinary tract infection, and kidney damage. Ureteral stenting is one of the most effective and least invasive clinical procedures for restoring urine drainage in the occluded ureter. A ureteric stent is a hollow tube with side-holes, which allows the urine to bypass the source of obstruction. Despite their clinical success, stents often suffer from failures and side effects that impact on both patient’s quality of life and costs for national health services. One of the most common complications is encrustation of the stent’s surface caused by calcifications, and particularly of side-holes, which are essential for maintaining urine drainage. Despite efforts have been devoted to develop novel materials and stent coatings; encrustation still remains a major complication. Few studies have however suggested that flow dynamics can potentially govern formation and deposition of encrusting crystals; however, improvements to the flow performance of stents are hindered by a lack of quantitative correlation between flow and encrustation processes. This study aims to develop a novel ureteric stent architecture, which flow performance is designed to reduce encrustation rates. In a first step of the study, a correlation between flow metrics – specifically wall shear stress (WSS) - and the accumulation of encrusting particles in stents was investigated. For this purpose, microfluidic-based models of the occluded and stented ureter (referred to as ‘stent-on-chip’ models) were developed, replicating the complexity of the WSS field at key hydrodynamic regions of interest (such as side-holes of the stent and the cavity formed by a ureteric occlusion). Using this model, a robust and inverse correlation between WSS and size/growth rate of encrusting deposits was demonstrated. Critical regions suffering from low WSS, and thus prone to faster encrustation, were also identified. These included holes that did not experience flow exchange between the stent and the ureter (referred to as ‘inactive’ holes), and the occluded cavity. The presence of these critical regions was also verified at a full-scale, both experimentally and numerically, to further validate the ability of microfluidic-based models to replicate relevant flow domains of a stented ureter. Stent-on-chip models were then employed as a technology platform to screen the effect of changing different architectural features of the stent. Changes to the thickness and shape of the side-holes were investigated, with a focus on those alterations that could be easily implemented within industrial constraints. A novel stent design, combining optimal thickness and a triangular hole shape, was developed; it showed significantly lower encrustation rates when compared to a standard stent design. Finally, a fabrication method was developed and validated for fabricating triangular side holes on a commercial ureteric stent. The developed stent design and fabrication method are easy-to-implement and thus the novel stent prototype can be potentially employed as an adjuvant approach to existing material and surface coatings against encrustation. Future pre-clinical investigations are required to evaluate the potential clinical benefit of the proposed stent design

Microfluidic system for chemiluminescence characterisation

Microfluidic technology (generally lab-on-a-chip) has been focused area of research since 90s and the main goal of this technology is to develop different chemical and biological techniques. It is quicker than the correspondent traditional techniques and consumes small volumes of material. One of the important functions in micro scale fluidic channels is mixing that its characteristics affected by scale because the viscous forces are more than inertial forces in this range of dimensions that provides laminar flow inside the channel; in this scale the mixing is defined by diffusion rather than turbulence.This dissertation presents the design of a microfluidic device and employing a combination of rapid prototype technology with polydimethylsiloxane (PDMS) for the fabrication. After the fabrication, chemiluminescence phenomenon is tested inside the device and the resultant images from the charge-coupled-device (CCD) camera are analysed using numerical analysis and image processing. Two sets of tests are performed for characterising the chemiluminescence in fabricated device. Preliminary tests to check the device and the chemicals’ behaviour and the actual test. In order to find the limit of detection, which is obtained as lower than 4 x 10-6 g of the dominant chemical (luminol) concentration in 100 ml of the solution, depends upon different parameters such as flow rate and the concentration of luminol are checked. The effect of the flow rate and the concentration on the maximum value and the decay length of the light intensity along the fluidic missing channels are then discussed. In the final part of the project, nanoparticles are used to improve the intensity of the light in the channel in order to improve the limit of detection of the system