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.

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.

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 stents.

Fluid mechanical modeling of the upper urinary tract.

The upper urinary tract (UUT) consists of kidneys and ureters, and is an integral part of the human urogenital system. Yet malfunctioning and complications of the UUT can happen at all stages of life, attributed to reasons such as congenital anomalies, urinary tract infections, urolithiasis and urothelial cancers, all of which require urological interventions and significantly compromise patients' quality of life. Therefore, many models have been developed to address the relevant scientific and clinical challenges of the UUT. Of all approaches, fluid mechanical modeling serves a pivotal role and various methods have been employed to develop physiologically meaningful models. In this article, we provide an overview on the historical evolution of fluid mechanical models of UUT that utilize theoretical, computational, and experimental approaches. Descriptions of the physiological functionality of each component are also given and the mechanical characterizations associated with the UUT are provided. As such, it is our aim to offer a brief summary of the current knowledge of the subject, and provide a comprehensive introduction for engineers, scientists, and clinicians who are interested in the field of fluid mechanical modeling of UUT. This article is categorized under: Cancer > Biomedical Engineering Infectious Diseases > Biomedical Engineering Reproductive System Diseases > Biomedical Engineering.

Continuous-Flow Production of Liposomes with a Millireactor under Varying Fluidic Conditions.

Continuous-flow production of liposomes using microfluidic reactors has demonstrated advantages compared to batch methods, including greater control over liposome size and size distribution and reduced reliance on post-production processing steps. However, the use of microfluidic technology for the production of nanoscale vesicular systems (such as liposomes) has not been fully translated to industrial scale yet. This may be due to limitations of microfluidic-based reactors, such as low production rates, limited lifetimes, and high manufacturing costs. In this study, we investigated the potential of millimeter-scale flow reactors (or millireactors) with a serpentine-like architecture, as a scalable and cost-effective route to the production of nanoscale liposomes. The effects on liposome size of varying inlet flow rates, lipid type and concentration, storage conditions, and temperature were investigated. Liposome size (i.e., mean diameter) and size dispersity were characterised by dynamic light scattering (DLS); z-potential measurements and TEM imaging were also carried out on selected liposome batches. It was found that the lipid type and concentration, together with the inlet flow settings, had significant effects on the properties of the resultant liposome dispersion. Notably, the millifluidic reactor was able to generate liposomes with size and dispersity ranging from 54 to 272 nm, and from 0.04 to 0.52 respectively, at operating flow rates between 1 and 10 mL/min. Moreover, when compared to a batch ethanol-injection method, the millireactor generated liposomes with a more therapeutically relevant size and size dispersity.

Strategies to Improve Patient Outcomes and QOL: Current Complications of the Design and Placements of Ureteric Stents.

Ureteric stents have played a vital role in relieving urinary obstruction in many urological conditions. Although they are extremely successful, stents have been associated with complications and reduced patients' health-related quality of life (HRQoL). There are many factors that may affect the quality and longevity of stents. In this review, we have highlighted the journey and innovation of ureteric stents through the modern day. A literature review was conducted to identify relevant articles over the last 20 years. There is a plethora of evidence with various indications for the use of ureteral stents and how they affect QoL. There is still ongoing research to develop the ideal stent with reduced encrustation, one that resists infection and is also comfortable for the patients. Stents made from metal alloys, polymers and biodegradable materials have unique properties in their own right but also have certain deficiencies. These have been discussed along with an overview of newly developed stents. Certain pharmacological adjuncts have also been highlighted that may be useful to improve patient's tolerance to stents. In summary, this paper describes the features of the different types of stents and the problems that are frequently encountered, including effect on patients' HRQoL and financial burden to healthcare providers.

A Microfluidic-Based Investigation of Bacterial Attachment in Ureteral Stents.

Obstructions of the ureter lumen can originate from intrinsic or extrinsic factors, such as kidney stones, tumours, or strictures. These can affect the physiological flow of urine from the kidneys to the bladder, potentially causing infection, pain, and kidney failure. To overcome these complications, ureteral stents are often deployed clinically in order to temporarily re-establish urinary flow. Despite their clinical benefits, stents are prone to encrustation and biofilm formation that lead to reduced quality of life for patients; however, the mechanisms underlying the formation of crystalline biofilms in stents are not yet fully understood. In this study, we developed microfluidic-based devices replicating the urodynamic field within different configurations of an occluded and stented ureter. We employed computational fluid dynamic simulations to characterise the flow dynamic field within these models and investigated bacterial attachment (Pseudomonas fluorescens) by means of crystal violet staining and fluorescence microscopy. We identified the presence of hydrodynamic cavities in the vicinity of a ureteric occlusion, which were characterised by low levels of wall shear stress (WSS < 40 mPa), and observed that initiation of bacterial attachment occurred in these specific regions of the stented ureter. Notably, the bacterial coverage area was directly proportional to the number of cavities present in the model. Fluorescence microscopy confirmed that the number density of bacteria was greater within cavities (3 bacteria·mm-2) when compared to side-holes of the stent (1 bacterium·mm-2) or its luminal surface (0.12·bacteria mm-2). These findings informed the design of a novel technological solution against bacterial attachment, which reduces the extent of cavity flow and increases wall shear stress over the stent's surface.

Latest advancements in ureteral stent technology.

Urological diseases such as tumours, kidney stones, or strictures in the ureter can lead to a number of health consequences, including life-threatening complications. Ureteral stents have been widely used as a valid solution to restore compromised urological function. Despite their clinical success, stents are subject to failure due to encrustation and biofilm formation, potentially leading to urinary tract infection. The current review focuses on recent advancements in ureteral stent technology, which have been reported in recent scientific journals or patents. Web of Science and Google Scholar have been used as a search engine to perform this review, using the keywords "Ureteral + Stent + Design", "Ureteral + Stent + Material + Coating", "Ureteric + Stent" and "Ureteral + Stent". A significant proportion of technological developments has focused on innovating the stent design to overcome migration and urinary reflux, as well as investigating novel materials and coatings to prevent biofilm formation, such as poly(N,N-dimethylacrylamide) (PDMMA) and swellable polyethylene glycol diacrylate (PEGDA). Biodegradable ureteral stents (BUS) have also emerged as a new generation of endourological devices, overcoming the "forgotten stent syndrome" and reducing healthcare costs. Moreover, efforts have been made to develop pre-clinical test methods, both experimental and computational, which could be employed as a screening platform to inform the design of novel stent technologies.

Continuous flow production of size-controllable niosomes using a thermostatic microreactor.

The new roles of vesicular systems in advanced biomedical, analytical and food science applications demand novel preparation processes designed to reach the new standards. Particle size and monodispersity have become essential properties to control. In this work, key parameters, involved in a microfluidic reactor with hydrodynamic flow focusing, were investigated in order to quantify their effects on niosomes morphology. Particular attention was given to temperature, which is both a requirement to handle non-ionic surfactants with phase transition temperature above RT, and a tailoring variable for size and monodispersity control. With this aim, niosomes with two different sorbitan esters and cholesterol as stabilizer were formulated. High resolution and conventional 3D-printing technologies were employed for the fabrication of microfluidic reactor and thermostatic systems, since this additive technology has been essential for microfluidics development in terms of cost-effective and rapid prototyping. A customised device to control temperature and facilitate visualization of the process was developed, which can be easily coupled with commercial inverted microscopes. The results demonstrated the capability of microfluidic production of niosomes within the full range of non-ionic surfactants and membrane stabilizers.

Particle Accumulation in Ureteral Stents Is Governed by Fluid Dynamics: In Vitro Study Using a "Stent-on-Chip" Model.

OBJECTIVE: To investigate the correlation between fluid dynamic processes and deposition of encrusting particles in ureteral stents. MATERIALS AND METHODS: Microfluidic models (referred to as "stent-on-chip" or SOC) were developed to replicate relevant hydrodynamic regions of a stented ureter, including drainage holes and the cavity formed by a ureteral obstruction. Computational fluid dynamic simulations were performed to determine the wall shear stress (WSS) field over the solid surfaces of the model, and the computational flow field was validated experimentally. Artificial urine was conveyed through the SOCs to measure the temporal evolution of encrustation through optical microscopy. RESULTS: It was revealed that drainage holes located well downstream of the obstruction had almost stagnant flow and low WSS (average 0.01 Pa, at 1 mL/min), and thus suffered from higher encrustation rates. On the contrary, higher levels of WSS in holes proximal to the obstruction (average ∼0.04 Pa, at 1 mL/min) resulted in lower encrustation rates in these regions. The cavity located nearby the obstruction was characterized by high levels of encrustation, because of the low WSS (average 1.6 × 10-4 Pa, at 1 mL/min) and the presence of flow vortices. Increasing the drainage flow rate from 1 to 10 mL/min resulted in significantly lower deposition of encrusting crystals. CONCLUSION: This study demonstrated an inverse correlation between deposition of encrusting bodies and the local WSS in a stented ureter model. Critical regions with low WSS and susceptible to encrustation were identified, including "inactive" side holes (i.e., with minimal or absent flow exchange between stent and ureter) and the cavity formed by a ureteral occlusion. Findings from this study can open new avenues for improving the stent's design through fluid dynamic optimization.

Advances in Ureteral Stent Design and Materials.

PURPOSE OF REVIEW: There are three technological parameters that play a key role on the performance of an ideal stent. These are its material, design and surface coating. This article highlights some fundamental developments that took place in these three areas of stent's technology, in order to contribute to the identification of an ideal stent. RECENT FINDINGS: In addition to technological developments concerning stent's material, design and surface coating, the flow dynamic performance of stents has recently attracted increasing attention. Notably, it has been postulated that the local flow field in a stent is correlated with the deposition of crystals and microorganisms. These findings could potentially revolutionise future stent's designs, and complement developments made on materials and coatings. The most relevant changes in materials, designs and surface coatings of ureteric stents are reviewed in this article. These are described in the context of a specific cause of stent's failure they aim to address, with a particular focus on encrustation and biofilm formation.

Easy-to-perform and cost-effective fabrication of continuous-flow reactors and their application for nanomaterials synthesis.

The translation of continuous-flow microreactor technology to the industrial environment has been limited by cost and complexity of the fabrication procedures and the requirement for specialised infrastructure. In the present study, we have developed a significantly more cost-effective and easy-to-perform fabrication method for the generation of optically transparent, continuous-flow reactors. The method combines 3D printing of master moulds with sealing of the PDMS channels' replica using a pressure-sensitive adhesive tape. Morphological characterisation of the 3D printed moulds was performed and reactors were fabricated with an approximately square-shaped cross-section of 1 mm2. Notably, they were tested for operation over a wide range of volumetric flow rates, up to 20 ml/min. Moreover, the fabrication time (i.e., from design to the finished product) was <1 day, at an average material cost of ∼£5. The flow reactors have been applied to the production of both inorganic nanoparticles (silver nanospheres) and organic vesicular systems (liposomes), and their performance compared with reactors produced using more laborious fabrication methods. Numerical simulations were performed to characterise the transport of fluids and chemical species within the devices. The developed fabrication method is suitable for scaled-up fabrication of continuous-flow reactors, with potential for application in biotechnology and nanomedicine.

Engineering solutions to ureteral stents: material, coating and design.

INTRODUCTION: An ideal stent would offer simple insertion and removal with no discomfort and/or migration, it would have no biofilm formation or encrustation and would also maintain the patient's quality of life. MATERIAL AND METHODS: In this mini-review, we outlined the engineering developments related to stent material, design and coating. RESULTS: There have been a wide variety of in-vitro, model-based, animal-based and clinical studies using a range of commercial and non-commercial stents. Ureteric stents have evolved since their first usage with a wider range of stent design, material and coating available for laboratory and clinical use. CONCLUSIONS: While engineering innovations have led to the evolution of stents, more work needs to be done to address the issues relating to stent encrustation and biofilm formation.

Analysis of the Diffusion Process by pH Indicator in Microfluidic Chips for Liposome Production.

In recent years, the development of nano- and micro-particles has attracted considerable interest from researchers and enterprises, because of the potential utility of such particles as drug delivery vehicles. Amongst the different techniques employed for the production of nanoparticles, microfluidic-based methods have proven to be the most effective for controlling particle size and dispersity, and for achieving high encapsulation efficiency of bioactive compounds. In this study, we specifically focus on the production of liposomes, spherical vesicles formed by a lipid bilayer encapsulating an aqueous core. The formation of liposomes in microfluidic devices is often governed by diffusive mass transfer of chemical species at the liquid interface between a solvent (i.e., alcohol) and a non-solvent (i.e., water). In this work, we developed a new approach for the analysis of mixing processes within microfluidic devices. The method relies on the use of a pH indicator, and we demonstrate its utility by characterizing the transfer of ethanol and water within two different microfluidic architectures. Our approach represents an effective route to experimentally characterize diffusion and advection processes governing the formation of vesicular/micellar systems in microfluidics, and can also be employed to validate the results of numerical modelling.

Tuning the chemiluminescence of a luminol flow using plasmonic nanoparticles.

We have discovered a strong increase in the intensity of the chemiluminescence of a luminol flow and a dramatic modification of its spectral shape in the presence of metallic nanoparticles. We observed that pumping gold and silver nanoparticles into a microfluidic device fabricated in polydimethylsiloxane prolongs the glow time of luminol. We have demonstrated that the intensity of chemiluminescence in the presence of nanospheres depends on the position along the microfluidic serpentine channel. We show that the enhancement factors can be controlled by the nanoparticle size and material. Spectrally, the emission peak of luminol overlaps with the absorption band of the nanospheres, which maximizes the effect of confined plasmons on the optical density of states in the vicinity of the luminol emission peak. These observations, interpreted in terms of the Purcell effect mediated by nano-plasmons, form an essential step toward the development of microfluidic chips with gain media. Practical implementation of the discovered effect will include improving the detection limits of chemiluminescence for forensic science, research in biology and chemistry, and a number of commercial applications.