Hemodynamics Challenges for the Navigation of Medical Microbots for the Treatment of CVDs.

Microbots have been considered powerful tools in minimally invasive medicine. In the last few years, the topic has been highly studied by researchers across the globe to further develop the capabilities of microbots in medicine. One of many applications of these devices is performing surgical procedures inside the human circulatory system. It is expected that these microdevices traveling along the microvascular system can remove clots, deliver drugs, or even look for specific cells or regions to diagnose and treat. Although many studies have been published about this subject, the experimental influence of microbot morphology in hemodynamics of specific sites of the human circulatory system is yet to be explored. There are numerical studies already considering some of human physiological conditions, however, experimental validation is vital and demands further investigations. The roles of specific hemodynamic variables, the non-Newtonian behavior of blood and its particulate nature at small scales, the flow disturbances caused by the heart cycle, and the anatomy of certain arteries (i.e., bifurcations and tortuosity of vessels of some regions) in the determination of the dynamic performance of microbots are of paramount importance. This paper presents a critical analysis of the state-of-the-art literature related to pulsatile blood flow around microbots.

Extensional Magnetorheology of Viscoelastic Human Blood Analogues Loaded with Magnetic Particles.

This study represents a pioneering work on the extensional magnetorheological properties of human blood analogue fluids loaded with magnetic microparticles. Dynabeads M-270 particles were dispersed in Newtonian and viscoelastic blood analogue fluids at 5% wt. Capillary breakup experiments were performed, with and without the influence of an external magnetic field aligned with the flow direction. The presence of the particles increased the viscosity of the fluid, and that increment was larger when embedded within a polymeric matrix. The application of an external magnetic field led to an even larger increment of the viscosity of the working fluids, as the formation of small aggregates induced an increment in the effective volume fraction of particles. Regarding the liquid bridge stability, the Newtonian blood analogue fluid remained as a Newtonian liquid exhibiting a pinch-off at the breakup time in any circumstance. However, in the case of the viscoelastic blood analogue fluid, the presence of the particles and the simultaneous application of the magnetic field enhanced the formation of the beads-on-a-string structure, as the Ohnesorge number remained basically unaltered, whereas the time of the experiment increased due to its larger viscosity, which resulted in a decrease in the Deborah Number. This result was confirmed with fluids containing larger concentrations of xanthan gum.

Rheological characterization of polymeric solutions used in spray drying process.

The present works contributes with a rheological characterization of the most commonly used polymers and solvents to formulate amorphous solid dispersions by means of spray drying process: copovidone, hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS) and a copolymer of methacrylic acid and methyl methacrylate (1:1 ratio and commercially known as Eudragit L100). The organic-based solutions are characterized in terms of surface tension, shear viscosity and relaxation time. HPMC and HPMCAS solutions exhibit shear thinning behaviour, i.e. decrease of shear viscosity with the increasing shear rate imposed, while the samples with Eudragit L100 can be considered Boger fluids, showing a constant viscosity but maintaining its viscoelastic character. Under uniaxial extensional flow, these polymers solutions exhibit a viscoelastic behavior with an increasing relaxation time with an increasing concentration, and in some cases showed a 'beads-on-string' effect. In contrast, copovidone showed a Newtonian fluid behavior, with the absence of elasticity. The fundamental understanding and characterization of the present work may be further applied to atomization modelling and support and expedite spray drying process development.

Critical overlap concentration and intrinsic viscosity data of xanthan gum aqueous solutions in dimethyl sulfoxide.

This is the supplementary information of the research paper "Haemodynamics around confined microscopic cylinders" by Rodrigues et al. [1]. The critical overlap concentration of entanglement of polymer coils indicates whether a polymer solution is dilute or semidilute. Here, the reader will find the determination of c * for xanthan gum aqueous solutions in 52 wt.% of dimethyl sulfoxide, often used as non-particulate blood analogues. From the shear flow curves of a dilution series of the polymer the zero-shear viscosities η 0 were obtained, allowing us to estimate the intrinsic viscosity [ η ] based on the xanthan gum concentration of the fluids. Two methodologies for doing so are described: using information from multi-concentration measurements and from a single polymer solution (rough estimate). With the intrinsic viscosity the determination of c * is straightforward.

Breakup of an electrified viscoelastic liquid bridge.

We study both numerically and experimentally the breakup of a viscoelastic liquid bridge formed between two parallel electrodes. The polymer solutions and applied voltages are those commonly used in electrospinning and near-field electrospinning. We solve the leaky-dielectric finitely extensible nonlinear elastic-Peterlin (FENE-P) model to describe the dynamical response of the liquid bridge under isothermal conditions. The results show that the surface charge screens the inner electric field perpendicular to the free surface over the entire dynamical process. The liquid bridge deformation produces a normal electric field on the outer side of the free surface that is commensurate with the axial one. The surface conduction does not significantly affect the current intensity in the time interval analyzed in the experiments. The force due to the shear electric stress becomes comparable to both the viscoelastic and surface tension forces in the last stage of the filament. However, it does not alter the elastocapillary balance in the filament. As a consequence, the extensional relaxation times measured from the filament exponential thinning approximately coincides with the stress relaxation time prescribed in the FENE-P model. The above results allow us to interpret correctly the experiments. In the experiments, we measure the filament electrical conductivity and extensional relaxation time for polyethylene oxide (PEO) dissolved in deionized water and in a mixture of water and glycerine. We compare the filament electrical conductivity with the value measured in hydrostatic conditions for the same estimated temperature. Good agreement was found for PEO dissolved in water + glycerine, which indicates that the change in the filament microscopic structure due to the presence of stretched polymeric chains does not significantly alter the ion mobility in the stretching direction. Significant deviations are found for PEO dissolved in deionized water. These deviations may be attributed to the heat transferred to the ambient, which is neglected in the calculation of the filament temperature. We measure the extensional relaxation time from the images acquired during the filament thinning. The relaxation times obtained in the first stage of the exponential thinning hardly depend on the applied voltage. Little but measurable influence of the applied voltage is found in the last phase of the filament thinning.

Direct Ink Writing Glass: A Preliminary Step for Optical Application.

In this paper, we present a preliminary study and conceptual idea concerning 3D printing water-sensitive glass, using a borosilicate glass with high alkali and alkaline oxide contents as an example in direct ink writing. The investigated material was prepared in the form of a glass frit, which was further ground in order to obtain a fine powder of desired particle size distribution. In a following step, inks were prepared by mixing the fine glass powder with Pluoronic F-127 hydrogel. The acquired pastes were rheologically characterized and printed using a Robocasting device. Differential scanning calorimetry (DSC) experiments were performed for base materials and the obtained green bodies. After sintering, scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses were carried out in order to examine microstructure and the eventual presence of crystalline phase inclusions. The results confirmed that the as obtained inks exhibit stable rheological properties despite the propensity of glass to undergo hydrolysis and could be adjusted to desirable values for 3D printing. No additional phase was observed, supporting the suitability of the designed technology for the production of water sensitive glass inks. SEM micrographs of the sintered samples revealed the presence of closed porosity, which may be the main reason of light scattering.

Microfluidics as a Platform for the Analysis of 3D Printing Problems.

Fused Filament Fabrication is an extrusion deposition technique in which a thermoplastic filament is melted, pushed through a nozzle and deposited to build, layer-by-layer, custom 3D geometries. Despite being one of the most widely used techniques in 3D printing, there are still some challenges to be addressed. One of them is the accurate control of the extrusion flow. It has been shown that this is affected by a reflux upstream the nozzle. Numerical models have been proposed for the explanation of this back-flow. However, it is not possible to have optical access to the melting chamber in order to confirm the actual behavior of this annular meniscus. Thus, microfluidics seems to be an excellent platform to tackle this fluid flow problem. In this work, a microfluidic device mimicking the 3D printing nozzle was developed, to study the complex fluid-flow behavior inside it. The principal aim was to investigate the presence of the mentioned back-flow upstream the nozzle contraction. As the microfluidic chip was fabricated by means of soft-lithography, the use of polymer melts was restricted due to technical issues. Thus, the working fluids consisted of two aqueous polymer solutions that allowed replicating the printing flow conditions in terms of Elasticity number and to develop a D e - R e flow map. The results demonstrate that the presence of upstream vortices, due to the elasticity of the fluid, is responsible for the back-flow problem.

Towards an Optimal Pressure Tap Design for Fluid-Flow Characterisation at Microscales.

Measuring fluid pressure in microchannels is difficult and constitutes a challenge to even the most experienced of experimentalists. Currently, to the best of the authors' knowledge, no optimal solution are being used for the design of pressure taps, nor guidelines concerning their shape and its relation with the accuracy of the readings. In an attempt to address this issue, a parametric study was devised to evaluate the performance of different pressure tap designs, 18 in total. These were obtained by combining three shape parameters: sub-channel width (w) and sub-channel-tap radius (R) or angle (α), while having the sub-channel length kept constant. For each configuration, pressure drop measurements were carried out along several lengths of a straight microfluidic rectangular channel and later compared to an analytical solution. The microchannels were fabricated out of PDMS using standard soft-lithography techniques, pressure drop was measured with differential pressure sensors, the test fluid was DI water and the flow conditions varied from creeping flow up to R e c ∼100. Pressure taps, having smooth contours (characterised by the radius R) and a sub-channel width (w) of 108 µ m , performed the best with results from that of radius R = 50 µ m only falling short of the theory by a mere ∼ 5 % .

Complex flow dynamics around 3D microbot prototypes.

A new experimental setup for the study of the complex flow dynamics around 3D microbot prototypes in a straight microchannel has been developed and assessed. The ultimate aim of this work is focused on the analysis of the morphology of different microbot prototypes to get a better insight into their efficiency when they swim through the main conduits of the human circulatory system. The setup consists of a fused silica straight microchannel with a 3D microbot prototype fastened in the center of the channel cross-section by an extremely thin support. Four different prototypes were considered: a cube, a sphere and two ellipsoids with aspect ratios of 1 : 2 and 1 : 4, respectively. Flow visualization and micro-particle image velocimetry (µPIV) measurements were performed using Newtonian and viscoelastic blood analogue fluids. An efficiency parameter, ℑ, to discriminate the prototypes in terms of flow disturbance has been proposed.

Particulate Blood Analogues Reproducing the Erythrocytes Cell-Free Layer in a Microfluidic Device Containing a Hyperbolic Contraction.

The interest in the development of blood analogues has been increasing recently as a consequence of the increment in the number of experimental hemodynamic studies and the difficulties associated with the manipulation of real blood in vitro because of ethical, economical or hazardous issues. Although one-phase Newtonian and non-Newtonian blood analogues can be found in the literature, there are very few studies related to the use of particulate solutions in which the particles mimic the behaviour of the red blood cells (RBCs) or erythrocytes. One of the most relevant effects related with the behaviour of the erythrocytes is a cell free layer (CFL) formation, which consists in the migration of the RBCs towards the center of the vessel forming a cell depleted plasma region near the vessel walls, which is known to happen in in vitro microcirculatory environments. Recent studies have shown that the CFL enhancement is possible with an insertion of contraction and expansion region in a straight microchannel. These effects are useful for cell manipulation or sorting in lab-on-chip studies. In this experimental study we present particulate Newtonian and non-Newtonian solutions which resulted in a rheological blood analogue able to form a CFL, downstream of a microfluidic hyperbolic contraction, in a similar way of the one formed by healthy RBCs.