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Dario Carugo

Dario Carugo
University of Oxford | OX · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)

PhD

About

162
Publications
37,751
Reads
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2,533
Citations
Citations since 2017
79 Research Items
2237 Citations
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Introduction
Dario is a Lecturer in the Department of Pharmaceutics at the UCL School of Pharmacy. He is coordinator of the Micro & Nano Therapies (MiNaTher.) research team. His research is focused in three complementary areas: (i) interventional medicine, (ii) ultrasound-mediated therapies, and (iii) microfluidic & sonofluidic reactors.
Additional affiliations
August 2020 - August 2020
University College London
Position
  • Lecturer
August 2018 - present
University of Southampton
Position
  • Lecturer
January 2016 - present
University of Oxford
Position
  • Visiting Research Fellow
Education
October 2009 - October 2012
University of Southampton
Field of study
  • Bioengineering
September 2006 - April 2009
Politecnico di Milano
Field of study
  • Biomedical Engineering
September 2003 - September 2006
Politecnico di Milano
Field of study
  • Biomedical Engineering

Publications

Publications (162)
Article
Full-text available
The transfer of material from phospholipid-coated microbubbles to cell membranes has been hypothesized to play a role in ultrasound-mediated drug delivery. In this study, we employed quantitative fluorescence microscopy techniques to investigate this phenomenon in both artificial and biological membrane bilayers in an acoustofluidic system. The res...
Article
Full-text available
An acoustofluidic device has been developed for concentrating vegetative bacteria in a continuous-flow format. We show that it is possible to overcome the disruptive effects of acoustic streaming which typically dominate for small target particles, and demonstrate flow rates compatible with the testing of drinking water. The device consists of a th...
Article
Full-text available
Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, i...
Article
In recent years, advancements in thefields of microfluidic and lab-on-a-chip technologies have provided unique opportunities for the implementation of nanomaterial production processes owing to the miniaturisation of the fluidic environment. It has been demonstrated that microfluidic reactors offer a range of advantages compared to conventional batch r...
Article
Full-text available
Echogenic particles, such as microbubbles and volatile liquid micro/nano droplets, have shown considerable potential in a variety of clinical diagnostic and therapeutic applications. The accurate prediction of their response to ultrasound excitation is however extremely challenging, and this has hindered the optimisation of techniques such as quant...
Article
Full-text available
Sclerotherapy is among the least invasive and most commonly utilised treatment options for varicose veins. Nonetheless, it does not cure varicosities permanently and recurrence rates are of up to 64%. Although sclerosing foams have been extensively characterised with respect to their bench-top properties, such as bubble size distribution and half-l...
Article
Full-text available
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...
Article
Full-text available
Bacterial biofilms are a major and ongoing concern for public health, featuring both inherited genetic resistance traits and a conferred innate tolerance to traditional antibiotic therapies. Consequently, there is a growing need for novel methods of drug delivery, to increase the efficacy of antimicrobial agents. This research evaluated the anti-bi...
Chapter
Full-text available
Stents and catheters are used to facilitate urine drainage within the urinary system. When such sterile implants are inserted into the urinary tract, ions, macromolecules and bacteria from urine, blood or underlying tissues accumulate on their surface. We presented a brief but comprehensive overview of future research strategies in the prevention o...
Chapter
Full-text available
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 fl...
Article
Full-text available
A 3D printed reactor-in-a-centrifuge (RIAC) was developed to produce drug nanocrystals. Quercetin nanocrystals were manufactured at varying operational and formulation conditions, and had a small size (190–302 nm) and low size dispersity (PDI < 0.1).
Article
Full-text available
The aim of this research was to explore the interaction between ultrasound-activated microbubbles (MBs) and Pseudomonas aeruginosa biofilms, specifically the effects of MB concentration, ultrasound exposure and substrate properties on bactericidal efficacy. Biofilms were grown using a Centre for Disease Control (CDC) bioreactor on polypropylene or...
Article
Full-text available
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 characterisa...
Article
Full-text available
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 comp...
Article
Full-text available
Sclerotherapy is one of the most common and least-invasive treatment methods for varicose veins. While bench-top properties of sclerosing foams (e.g., bubble size distribution and foam half-life) have been studied previously, their flow behaviour and its relationship to therapeutic efficacy remain largely uncharacterised. To address this research g...
Article
No PDF available ABSTRACT Interactions between oscillating microbubbles and cells are of fundamental importance in understanding cell behaviour, including mechanotransduction, during therapeutic microbubble treatment. However, it is challenging to quantify cell deformation due to the short time domains at which microbubble-induced deformations occu...
Article
Full-text available
Impaired fracture healing impacts patients’ quality of life and imposes a financial burden on healthcare services. Up to 10% of bone fractures result in delayed/non-union fractures, for which new treatments are urgently required. However, systemic delivery of bone anabolic molecules is often sub-optimal and can lead to significant side effects. In...
Article
Surfactant-coated gas microbubbles are widely used as contrast agents in ultrasound imaging and increasingly in therapeutic applications. The response of microbubbles to ultrasound can be strongly influenced by their size and coating properties, and hence the production method. Ultrasonic emulsification (sonication) is the most commonly employed me...
Article
Background Urinary stents have been around for the last 4 decades, urinary catheters even longer. They are associated with infections, encrustation, migration and patient discomfort. Research efforts to improve them have shifted onto molecular and cellular levels. ENIUS brought together translational scientists to improve urinary implants and reduc...
Article
It is widely recognised that flow-reactors offer greater control over the stoichiometry of chemical reactions when compared to batch methods, since they provide finer and more predictable regulation over the transport of fluids and chemical species. These characteristics are of critical importance in the context of nanoparticle production, since th...
Article
A portable device for the rapid concentration of Bacillus subtilis var niger (BG) spores using a thin-reflector acoustofluidic configuration is described. BG spores form an important lab analogue for Bacillus anthracis spores, a serious health and bio-terrorism risk. Existing systems for spore detection have limitations on detection time and limits...
Chapter
We present a new method for controllable loading of cell models in an ultrasonic (20 kHz) regime. The protocol is based on the inertial-based ultrasonic shaking test and allows to deform cells in the range of few mm/m to help understand potential consequences of repeated loading characteristic of ultrasonic cutting.
Article
A combination of ultra high-speed optical imaging (5 x 10^6 frames/s), B-mode ultrasound and passive cavitation detection was used to study the vaporization process and determine both the acoustic droplet vaporization (ADV) and inertial cavitation (IC) thresholds of phospholipid-coated perfluorobutane nanodroplets (PFB-NDs; diameter 237 nm ±16 nm)....
Article
Full-text available
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 in...
Article
Full-text available
Liquid perfluorocarbon nanodroplets (NDs) are an attractive alternative to microbubbles (MBs) for ultrasound-mediated therapeutic and diagnostic applications. ND size and size distribution have a strong influence on their behaviour in vivo, including extravasation efficiency, circulation time, and response upon ultrasound stimulation. Thus, it is d...
Article
Full-text available
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 h...
Conference Paper
Full-text available
Impaired fracture healing impacts patients’ quality of life and imposes a financial burden on healthcare services. Up to 10% of bone fractures result in delayed/non-union fractures, for which new treatments are urgently required. However, systemic delivery of bone anabolic molecules is often sub-optimal and can lead to significant side effects. In...
Article
Full-text available
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...
Article
No PDF available ABSTRACT Surfactant-coated gas microbubbles are widely used as contrast agents in ultrasound imaging and increasingly for therapeutic applications. It has been shown that the acoustic response of microbubbles is determined by their size and coating properties and hence depends upon both their chemical composition and the manufactur...
Article
Full-text available
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 h...
Article
Studies on the bioeffects produced by ultrasound and microbubbles have focused primarily on transport in bulk tissue, drug uptake by individual cells, and disruption of biological membranes. Relatively little is known about the physical perturbations and fluid dynamics of the intracellular environment during ultrasound exposure. To investigate this...
Article
Full-text available
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 i...
Article
Full-text available
Model membrane systems are essential tools for the study of biological processes in a simplified setting to reveal the underlying physicochemical principles. As cell-derived membrane systems, giant plasma membrane vesicles (GPMVs) constitute an intermediate model between live cells and fully artificial structures. Certain applications, however, req...
Article
Full-text available
Model membrane systems are essential tools for the study of biological processes in a simplified setting to reveal the underlying physicochemical principles. As cell-derived membrane systems, giant plasma membrane vesicles (GPMVs) constitute an intermediate model between live cells and fully artificial structures. Certain applications, however, req...
Preprint
Full-text available
Model membrane systems are essential tools for biology, enabling study of biological processes in a simplified setting to reveal the underlying physicochemical principles. As cell-derived membrane systems, giant plasma membrane vesicles (GPMVs) constitute an intermediate model between native cellular plasma and artificial membranes. Certain applica...
Article
Microbubbles stabilised by an outer lipid shell have been studied extensively for both diagnostic and therapeutic applications. The shell composition can significantly influence microbubble behaviour, but performing quantitative measurements of shell properties is challenging. The aim of this study was to investigate the use of spectral imaging to...
Article
No PDF available ABSTRACT Impaired fracture healing is a major financial burden for healthcare services; 5%–10% of bone fractures result in non-unions, and there is no clinically approved systemic therapy. This study characterises acoustically stimulated microbubbles (MBs) and nanodroplets (NDs) as non-invasive ultrasound responsive vehicles for th...
Article
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 inte...
Article
Full-text available
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...
Article
Full-text available
Bacterial biofilms are an ever-growing concern for public health; featuring both inherited genetic resistance and a conferred innate tolerance to traditional antibiotic therapies. Consequently, there is a growing interest in novel methods of drug delivery, in order to increase the efficacy of antimicrobial agents. One such method is the use of acou...
Article
Full-text available
Since the first reports on foam sclerotherapy, multiple studies have been conducted to determine the physical properties and behavior of foams, but relatively little is known about their biological effects on the endothelial cells lining the vessel wall. Moreover, a systematic comparison of the biological performance of foams produced with differen...
Article
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, we...
Article
Full-text available
Foam sclerotherapy is clinically employed to treat varicose veins. It involves intravenous injection of foamed surfactant agents causing endothelial wall damage and vessel shrinkage, leading to subsequent neovascularization. Foam production methods used clinically include manual techniques, such as the Double Syringe System (DSS) and Tessari (TSS)...
Article
Full-text available
The development of new modalities for high-efficiency intracellular drug delivery is a priority for a number of disease areas. One such area is urinary tract infection (UTI), which is one of the most common infectious diseases globally and which imposes an immense economic and healthcare burden. Common uropathogenic bacteria have been shown to inva...
Article
Full-text available
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 failu...
Article
Full-text available
Microbubble-enhanced sonothrombolysis is a promising approach to increase the safety and efficacy of current pharmacological treatments for ischemic stroke. Maintaining therapeutic concentrations of microbubbles and drugs at the clot site however poses a challenge. The objective of this study was to investigate the efficacy of magnetic microbubble...
Article
Full-text available
Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. Whilst the i...
Conference Paper
Full-text available
In this paper, we propose a simple acoustofluidic method for production of microbubble contrast agents in disposable microfluidic chips by the use of a low-frequency ultrasound transducer and a temperature controller unit. The technique is used to increase the lifetime and to narrow down the size distribution of the microbubbles as compared to trad...
Conference Paper
Full-text available
Conference abstract detailing the use of lipid shelled microbubbles utilised in the treatment of bacterial biofilms - ISBN 978-1-9996465-0-9
Article
Full-text available
The study of the effects of ultrasound-induced acoustic cavitation on biological structures is an active field in biomedical research. Of particular interest for therapeutic applications is the ability of oscillating microbubbles to promote both cellular and tissue membrane permeabilisation and to improve the distribution of therapeutic agents in t...
Article
Full-text available
Objective. To investigate the correlation between fluid dynamic processes and deposition of encrusting particles in ureteric 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 ure...
Article
Full-text available
Acoustically-responsive microbubbles have been widely researched as agents for both diagnostic and therapeutic applications of ultrasound. Recently, there has also been considerable interest in magnetically functionalised microbubbles as multi-modality imaging agents and carriers for magnetically targeted drug delivery. The latter application in pa...
Article
Full-text available
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. R...
Article
Microbubbles are currently in clinical use as ultrasound contrast agents and under active investigation as mediators of ultrasound therapy. To improve the theranostic potential of microbubbles, nanoparticles can be attached to the bubble shell for imaging, targeting and/or enhancement of acoustic response. Existing methods for fabricating particle-...
Article
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 cost-effective and easy-to-perform fabrication method for the generation of optica...
Conference Paper
High concentration antibiotics (>50 µg/ml) can achieve a desired 99.9% bacterial killing in biofilms, but through repeated use bacteria are likely to develop AMR. We have shown that ultrasound-activated microbubbles have potential for enhancing the antimicrobial activity of low-concentration (<10 µg/ml) antibiotics on Pseudomonas Aeruginosa biofilm...
Article
Full-text available
Development of remote stimulation techniques for neuronal tissues represents a challenging goal. Among the potential methods, mechanical stimuli are the most promising vectors to convey information non-invasively into intact brain tissue. In this context, selective mechano-sensitization of neuronal circuits would pave the way to develop a new cell-...
Chapter
Functionalised microbubbles have shown considerable potential both as contrast agents for ultrasound imaging and as a means of enhancing ultrasound mediated therapy. With the development of advanced techniques such as quantitative ultrasound imaging and targeted drug delivery, the accurate prediction of their response to ultrasound excitation is be...
Conference Paper
Full-text available
Sclerotherapy is currently employed to effectively treat varicose veins, and relies on the injection of liquid or foamed agents causing endothelial wall damage, vessel shrinkage, and subsequent neovascularization. Pre-clinical in-vitro studies are typically conducted to characterize the performance of sclerosing agents; however, they often do not r...
Poster
Full-text available
In this study, we adopted a bottom-up approach to develop robust models for pre-clinical testing of the mechanical and biological performance of sclerosing agents.