Search results
Found 30896 matches for
Life under flow: A novel microfluidic device for the assessment of anti-biofilm technologies.
In the current study, we have developed and fabricated a novel lab-on-a-chip device for the investigation of biofilm responses, such as attachment kinetics and initial biofilm formation, to different hydrodynamic conditions. The microfluidic flow channels are designed using computational fluid dynamic simulations so as to have a pre-defined, homogeneous wall shear stress in the channels, ranging from 0.03 to 4.30 Pa, which are relevant to in-service conditions on a ship hull, as well as other man-made marine platforms. Temporal variations of biofilm formation in the microfluidic device were assessed using time-lapse microscopy, nucleic acid staining, and confocal laser scanning microscopy (CLSM). Differences in attachment kinetics were observed with increasing shear stress, i.e., with increasing shear stress there appeared to be a delay in bacterial attachment, i.e., at 55, 120, 150, and 155 min for 0.03, 0.60, 2.15, and 4.30 Pa, respectively. CLSM confirmed marked variations in colony architecture, i.e.,: (i) lower shear stresses resulted in biofilms with distinctive morphologies mainly characterised by mushroom-like structures, interstitial channels, and internal voids, and (ii) for the higher shear stresses compact clusters with large interspaces between them were formed. The key advantage of the developed microfluidic device is the combination of three architectural features in one device, i.e., an open-system design, channel replication, and multiple fully developed shear stresses.
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.
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.
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.
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.
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.
An artificial model for studying fluid dynamics in the obstructed and stented ureter.
Fluid dynamics in the obstructed and stented ureter represents a non-trivial subject of investigation since, after stent placement, the urine can flow either through the stent lumen or in the extra-luminal space located between the stent wall and the ureteric inner wall. Fluid dynamic investigations can help understanding the phenomena behind stent failure (e.g. stent occlusions due to bacterial colonization and encrustations), which may cause kidney damage due to the associated high pressures generated in the renal pelvis. In this work a microfluidic-based transparent device (ureter model, UM) has been developed to simulate the fluid dynamic environment in a stented ureter. UM geometry has been designed from measurements on pig ureters. Pressure in the renal pelvis compartment has been measured against three variables: fluid viscosity (μ), volumetric flow rate (Q) and level of obstruction (OB%). The measurements allowed a quantification of the critical combination of μ, Q and OB% values which may lead to critical pressure levels in the kidney. Moreover, an example showing the possibility of applying particle image velocimetry (PIV) technology to the developed microfluidic device is provided.
An experimental and computational study of the hydrodynamics of high-velocity water microdrops for interproximal tooth cleaning.
The flow field and local hydrodynamics of high-velocity water microdrops impacting the interproximal (IP) space of typodont teeth were studied experimentally and computationally. Fourteen-day old Streptococcus mutans biofilms in the IP space were treated by a prototype AirFloss delivering 115 µL of water at a maximum exit-velocity of 60 ms(-1) in a 33-ms burst. Using high-speed imaging, footage was generated showing the details of the burst, and demonstrating the removal mechanism of the biofilms. Footage was also generated to characterize the viscoelastic behavior of the biofilms when impacted by an air-only burst, which was compared to the water burst. Image analysis demonstrated the importance of fluid forces on the removal pattern of interdental biofilms. X-ray micro-Computed Tomography (µ-CT) was used to obtain 3D images of the typodont and the IP spaces. Computational Fluid Dynamics (CFD) simulations were performed to study the effect of changing the nozzle position and design on the hydrodynamics within the IP space. Results confirmed our previous data regarding the wall shear stress generated by high-velocity water drops which dictated the efficacy of biofilm detachment. Finally, we showed how CFD models could be used to optimize water drop or burst design towards a more effective biofilm removal performance.
A novel biomimetic analysis system for quantitative characterisation of sclerosing foams used for the treatment of varicose veins.
A novel analysis system for the quantification of sclerosing foam properties under clinically relevant conditions was developed with the purpose of establishing a robust methodology for comparative characterisation of different foam formulations and production strategies. The developed biomimetic-inspired model comprised of 4 or 10 mm inner diameter polytetrafluoroethylene tubing, filled with a blood substitute and fixed to a platform with an adjustable inclination angle. Sclerosing foams were produced by mixing polidocanol with either atmospheric air or 100 % CO₂, using a double-syringe system method. Individual foams were injected into the tube, while videos were captured simultaneously. Videos were then transferred to an in-house computational foam analysis system (CFAS) which performed a sequence of semi-automated operations, allowing quantitative characterisation of sclerosing foam dynamic behaviour. Using CFAS, degradation rates of different foams were measured and the effect of gas composition, liquid sclerosant concentration and time delay between foam production and injection were evaluated.
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.
Review of the Development of Methods for Characterization of Microspheres for Use in Embolotherapy: Translating Bench to Cathlab.
Therapeutic embolotherapy is the deliberate occlusion of a blood vessel within the body, which can be for the prevention of internal bleeding, stemming of flow through an arteriovenous malformation, or occlusion of blood vessels feeding a tumor. This is achieved using a wide selection of embolic devices such as balloons, coils, gels, glues, and particles. Particulate embolization is often favored for blocking smaller vessels, particularly within hypervascularized tumors, as they are available in calibrated sizes and can be delivered distally via microcatheters for precise occlusion with associated locoregional drug delivery. Embolic performance has been traditionally evaluated using animal models, but with increasing interest in the 3R's (replacement, reduction, refinement), manufacturers, regulators, and clinicians have shown interest in the development of more sophisticated in vitro methods for evaluation and prediction of in vivo performance. Herein the current progress in developing bespoke techniques incorporating physical handling, fluid dynamics, occlusive behavior, and sustained drug elution kinetics within vascular systems is reviewed. While it is necessary to continue to validate the safety of such devices in vivo, great strides have been made in the development of bench tests that better predict the behavior of these products aligned with the principles of the 3R's.
Benefits of polidocanol endovenous microfoam (Varithena®) compared with physician-compounded foams.
OBJECTIVE: To compare foam bubble size and bubble size distribution, stability, and degradation rate of commercially available polidocanol endovenous microfoam (Varithena®) and physician-compounded foams using a number of laboratory tests. METHODS: Foam properties of polidocanol endovenous microfoam and physician-compounded foams were measured and compared using a glass-plate method and a Sympatec QICPIC image analysis method to measure bubble size and bubble size distribution, Turbiscan™ LAB for foam half time and drainage and a novel biomimetic vein model to measure foam stability. Physician-compounded foams composed of polidocanol and room air, CO2, or mixtures of oxygen and carbon dioxide (O2:CO2) were generated by different methods. RESULTS: Polidocanol endovenous microfoam was found to have a narrow bubble size distribution with no large (>500 µm) bubbles. Physician-compounded foams made with the Tessari method had broader bubble size distribution and large bubbles, which have an impact on foam stability. Polidocanol endovenous microfoam had a lower degradation rate than any physician-compounded foams, including foams made using room air (p
Continuous-flow production of polymeric micelles in microreactors: experimental and computational analysis.
We report the development of a microfluidic-based process for the production of polymeric micelles (PMs) in continuous-flow microreactors where Pluronic® tri-block copolymer is used as model polymeric biomaterial relating to drug delivery applications. A flow focusing configuration is used enabling a controllable, and fast mixing process to assist the formation of polymeric micelles through nanoprecipitation which is triggered by a solvent exchange process when organic solutions of the polymer mixed with a non-solvent. We experientially investigate the effect of polymer concentration, flow rate ratio and microreactor dimension on the PMs size characteristics. The mixing process within the microfluidic reactors is further analyzed by computational modeling in order to understand the hydrodynamic process and its implication for the polymeric micelles formation process. The results obtained show that besides the effect of the flow rate ratio, the chemical environment in which the aggregation takes place plays an important role in determining the dimensional characteristics of the produced polymeric micelles. It is demonstrated that microfluidic reactors provide a useful platform for the continuous-flow production of polymeric micelles with improved controllability, reproducibility, and homogeneity of the size characteristics.
A microfluidic device for the characterisation of embolisation with polyvinyl alcohol beads through biomimetic bifurcations.
A microfluidic based device has been developed for the characterisation of embolisation behaviour with polyvinyl alcohol (PVA) hydrogel beads within a microchannel network with bifurcations which mimic the blood vessel network. Both distal and proximal embolisations were achieved within the PMMA-made microdevice exhibiting comparable embolisation characteristics with those observed in vivo. Results showed that small beads allowed more distal embolisations with a reduced control of the spatial location of occlusion sites. In contrast, large beads generated effective proximal embolisations with an improved reproducibility of embolisation performance. Embolic bead hydrodynamics, partitioning at bifurcations, penetration through microchannels and embolisation locations across the channel network were characterised by quantifying the effects of embolic bead size, bead concentration, channel geometry and fluidic conditions. This development provided further insights into the physical principles governing embolisation performances within the constructed microdevices allowing the improvement of the predictability and controllability of the clinical process outcomes. Furthermore, it can potentially provide a useful platform for preclinical research as an alternative to animal models, with an ultimate goal to reduce the amount of animal testing.
Foam-in-vein: A review of rheological properties and characterization methods for optimization of sclerosing foams.
Varicose veins are chronic venous defects that affect >20% of the population in developed countries. Among potential treatments, sclerotherapy is one of the most commonly used. It involves endovenous injection of a surfactant solution (or foam) in varicose veins, inducing damage to the endothelial layer and subsequent vessel sclerosis. Treatments have proven to be effective in the short-term, however recurrence is reported at rates of up to 64% 5-year post-treatment. Thus, once diagnosed with varicosities there is a high probability of a permanently reduced quality of life. Recently, foam sclerotherapy has become increasingly popular over its liquid counterpart, since foams can treat larger and longer varicosities more effectively, they can be imaged using ultrasound, and require lower amounts of sclerosing agent. In order to minimize recurrence rates however, an investigation of current treatment methods should lead to more effective and long-lasting effects. The literature is populated with studies aimed at characterizing the fundamental physics of aqueous foams; nevertheless, there is a significant need for appropriate product development platforms. Despite successfully capturing the microstructural evolution of aqueous foams, the complexity of current models renders them inadequate for pharmaceutical development. This review article will focus on the physics of foams and the attempts at optimizing them for sclerotherapy. This takes the form of a discussion of the most recent numerical and experimental models, as well as an overview of clinically relevant parameters. This holistic approach could contribute to better foam characterization methods that patients may eventually derive long term benefit from.
Acoustically responsive polydopamine nanodroplets: A novel theranostic agent.
Ultrasound-induced cavitation has been used as a tool of enhancing extravasation and tissue penetration of anticancer agents in tumours. Initiating cavitation in tissue however, requires high acoustic intensities that are neither safe nor easy to achieve with current clinical systems. The use of cavitation nuclei can however lower the acoustic intensities required to initiate cavitation and the resulting bio-effects in situ. Microbubbles, solid gas-trapping nanoparticles, and phase shift nanodroplets are some examples in a growing list of proposed cavitation nuclei. Besides the ability to lower the cavitation threshold, stability, long circulation times, biocompatibility and biodegradability, are some of the desirable characteristics that a clinically applicable cavitation agent should possess. In this study, we present a novel formulation of ultrasound-triggered phase transition sub-micrometer sized nanodroplets (~400 nm) stabilised with a biocompatible polymer, polydopamine (PDA). PDA offers some important benefits: (1) facile fabrication, as dopamine monomers are directly polymerised on the nanodroplets, (2) high polymer biocompatibility, and (3) ease of functionalisation with other molecules such as drugs or targeting species. We demonstrate that the acoustic intensities required to initiate inertial cavitation can all be achieved with existing clinical ultrasound systems. Cell viability and haemolysis studies show that nanodroplets are biocompatible. Our results demonstrate the great potential of PDA nanodroplets as an acoustically active nanodevice, which is highly valuable for biomedical applications including drug delivery and treatment monitoring.
Reducing deposition of encrustation in ureteric stents by changing the stent architecture: A microfluidic-based investigation.
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.