Purpose of ReviewThere 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 FindingsIn 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.SummaryThe 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.

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.

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.

Ureteric stents are clinically deployed to retain ureteral patency in the presence of an obstruction of the ureter lumen. Despite the fact that multiple stent designs have been researched in recent years, encrustation and biofilm-associated infections remain significant complications of ureteral stenting, potentially leading to the functional failure of the stent. It has been suggested that “inactive” side-holes of stents may act as anchoring sites for encrusting crystals, as they are associated with low wall shear stress (WSS) levels. Obstruction of side-holes due to encrustation is particularly detrimental to the function of the stent, since holes provide a path for urine to by-pass the occlusion. Therefore, there is an unmet need to develop novel stents to reduce deposition of encrusting particles at side-holes. In this study, we employed a stent-on-chip microfluidic model of the stented and occluded ureter to investigate the effect of stent architecture on WSS distribution and encrustation over its surface. Variations in the stent geometry encompassed (i) the wall thickness and (ii) the shape of side-holes. Stent thickness was varied in the range 0.3-0.7 mm, while streamlined side-holes of triangular shape were evaluated (with a vertex angle in the range 45°-120°). Reducing the thickness of the stent increased WSS and thus reduced the encrustation rate at side-holes. A further improvement in performance was achieved by using side-holes with a triangular shape; notably, a 45° vertex angle showed superior performance compared to other angles investigated, resulting in a significant increase in WSS within “inactive” side-holes. In conclusion, combining the optimal stent thickness (0.3 mm) and hole vertex angle (45°) resulted in a ∼90% reduction in encrustation rate within side-holes, compared to a standard design. If translated to a full-scale ureteric stent, this optimised architecture has the potential for significantly increasing the stent lifetime while reducing clinical complications.

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.

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.

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

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 mm. 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.