Oscillation dynamics of embolic microspheres in flows with red blood cell suspensions

Dynamic nature of particle motion in blood flow is an important determinant of embolization based cancer therapy. Yet, the manner in which the presence of high volume fraction of red blood cells influences the particle dynamics remains unknown. Here, by investigating the motions of embolic microspheres in pressure-driven flows of red blood cell suspensions through capillaries, we illustrate unique oscillatory trends in particle trajectories, which are not observable in Newtonian fluid flows. Our investigation reveals that such oscillatory behavior essentially manifests when three simultaneous conditions, namely, the Reynolds number beyond a threshold limit, degree of confinement beyond a critical limit, and high hematocrit level, are fulfilled simultaneously. Given that these conditions are extremely relevant to fluid dynamics of blood or polymer flow, the observations reported here bear significant implications on embolization based cancer treatment as well as for complex multiphase fluidics involving particle

Investigating the flow dynamics in the obstructed and stented ureter by means of a biomimetic artificial model

Double-J stenting is the most common clinical method employed to restore the upper urinary tract drainage, in the presence of a ureteric obstruction. After implant, stents provide an immediate pain relief by decreasing the pressure in the renal pelvis (P). However, their long-term usage can cause infections and encrustations, due to bacterial colonization and crystal deposition on the stent surface, respectively. The performance of double-J stents - and in general of all ureteric stents - is thought to depend significantly on urine flow field within the stented ureter. However very little fundamental research about the role played by fluid dynamic parameters on stent functionality has been conducted so far. These parameters are often difficult to assess in-vivo, requiring the implementation of laborious and expensive experimental protocols. The aim of the present work was therefore to develop an artificial model of the ureter (i.e. ureter model, UM) to mimic the fluid dynamic environment in a stented ureter. The UM was designed to reflect the geometry of pig ureters, and to investigate the values of fluid dynamic viscosity (μ), volumetric flow rate (Q ) and severity of ureteric obstruction (OB%) which may cause critical pressures in the renal pelvis. The distributed obstruction derived by the sole stent insertion was also quantified. In addition, flow visualisation experiments and computational simulations were performed in order to further characterise the flow field in the UM. Unique characteristics of the flow dynamics in the obstructed and stented ureter have been revealed with using the developed UM

An acoustic device for ultra high-speed quantification of cell strain during cell-microbubble interaction

Microbubbles utilize high-frequency oscillations under ultrasound stimulation to induce a range of therapeutic effects in cells, often through mechanical stimulation and permeabilization of cells. One of the largest challenges remaining in the field is the characterization of interactions between cells and microbubbles at therapeutically relevant frequencies. Technical limitations, such as employing sufficient frame rates and obtaining sufficient image resolution, restrict the quantification of the cell's mechanical response to oscillating microbubbles. Here, a novel methodology was developed to address many of these limitations and improve the image resolution of cell-microbubble interactions at high frame rates. A compact acoustic device was designed to house cells and microbubbles as well as a therapeutically relevant acoustic field while being compatible with a Shimadzu HPV-X camera. Cell viability tests confirmed the successful culture and proliferation of cells, and the attachment of DSPC- and cationic DSEPC-microbubbles to osteosarcoma cells was quantified. Microbubble oscillation was observed within the device at a frame rate of 5 million FPS, confirming suitable acoustic field generation and ultra high-speed image capture. High spatial resolution in these images revealed observable deformation in cells following microbubble oscillation and supported the first use of digital image correlation for strain quantification in a single cell. The novel acoustic device provided a simple, effective method for improving the spatial resolution of cell-microbubble interaction images, presenting the opportunity to develop an understanding of the mechanisms driving the therapeutic effects of oscillating microbubbles upon ultrasound exposure.</p

Tailoring the size of ultrasound responsive lipid-shelled nanodroplets by varying production parameters and environmental conditions

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 to ultrasound stimulation. Thus, it is desirable to identify ways to tailor the ND size and size distribution during manufacturing. In this study phospholipid-coated NDs, comprising a perfluoro-n-pentane (PFP) core stabilised by a DSPC/PEG40s (1,2-distearoyl-sn-glycero-3-phosphocholine and polyoxyethylene(40)stearate, 9:1 molar ratio) shell, were produced in phosphate-buffered saline (PBS) by sonication. The effect of the following production-related parameters on ND size was investigated: PFP concentration, power and duration of sonication, and incorporation of a lipophilic fluorescent dye. ND stability was also assessed at both 4 °C and 37 °C. When a sonication pulse of 6 s and 15% duty cycle was employed, increasing the volumetric concentration of PFP from 5% to 15% v/v in PBS resulted in an increase in ND diameter from 215.8 ± 16.8 nm to 408.9 ± 171.2 nm. An increase in the intensity of sonication from 48 to 72 W (with 10% PFP v/v in PBS) led to a decrease in ND size from 354.6 ± 127.2 nm to 315.0 ± 100.5 nm. Increasing the sonication time from 20 s to 40 s (using a pulsed sonication with 30% duty cycle) did not result in a significant change in ND size (in the range 278-314 nm); however, when it was increased to 60 s, the average ND diameter reduced to 249.7 ± 9.7 nm, which also presented a significantly lower standard deviation compared to the other experimental conditions investigated (i.e., 9.7 nm vs. &gt; 49.4 nm). The addition of the fluorescent dye DiI at different molar ratios did not affect the ND size distribution. NDs were stable at 4 °C for up to 6 days and at 37 °C for up to 110 min; however, some evidence of ND-to-MB phase transition was observed after 40 min at 37 °C. Finally, phase transition of NDs into MBs was demonstrated using a tissue-mimicking flow phantom under therapeutic ultrasound exposure conditions (ultrasound frequency: 0.5 MHz, acoustic pressure: 2-4 MPa, and pulse repetition frequency: 100 Hz).</p

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

Investigation of the acoustic vaporization threshold of lipid-coated perfluorobutane nanodroplets using both high-speed optical imaging and acoustic methods

A combination of ultrahigh-speed optical imaging (5 × 106 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 ± 16 nm). PFB NDs have not previously been studied with ultrahigh-speed imaging and were observed to form individual microbubbles (1-10 μm) within two to three cycles and subsequently larger bubble clusters (10-50 μm). The ADV and IC thresholds did not statistically significantly differ and decreased with increasing pulse length (20-20,000 cycles), pulse repetition frequency (1-100 Hz), concentration (108-1010 NDs/mL), temperature (20°C-45°C) and decreasing frequency (1.5-0.5 MHz). Overall, the results indicate that at frequencies of 0.5, 1.0 and 1.5 MHz, PFB NDs can be vaporized at moderate peak negative pressures (&lt;2.0 MPa), pulse lengths and pulse repetition frequencies. This finding is encouraging for the use of PFB NDs as cavitation agents, as these conditions are comparable to those required to achieve therapeutic effects with microbubbles, unlike those reported for higher-boiling-point NDs. The differences between the optically and acoustically determined ADV thresholds, however, suggest that application-specific thresholds should be defined according to the biological/therapeutic effect of interest.</p

Potential strategies to prevent encrustations on urinary stents and catheters – thinking outside the box:a European network of multidisciplinary research to improve urinary stents (ENIUS) initiative

Abstract Introduction: 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 reduce morbidity. Methods &amp; materials: A working group within the ENIUS network was tasked with assessing future research lines for the improvement of urinary implants. Topics were researched systematically using Embase and PubMed databases. Clinicaltrials.gov was consulted for ongoing trials. Areas covered: Relevant topics were coatings with antibodies, enzymes, biomimetics, bioactive nano-coats, antisense molecules, and engineered tissue. Further, pH sensors, biodegradable metals, bactericidal bacteriophages, nonpathogenic uropathogens, enhanced ureteric peristalsis, electrical charges, and ultrasound to prevent stent encrustations were addressed. Expert opinion: All research lines addressed in this paper seem viable and promising. Some of them have been around for decades but are yet to proceed to clinical application (i.e. tissue engineering). Others are very recent and, at least in urology, still only conceptual (i.e. antisense molecules). Perhaps the most important learning point resulting from this pan-European multidisciplinary effort is that collaboration between all stakeholders is not only fruitful but also truly essential