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.

Electrospinning covalently cross-linking biocompatible hydrogelators.

Many hydrogel materials of interest are homogeneous on the micrometer scale. Electrospinning, the formation of sub-micrometer to micrometer diameter fibers by a jet of fluid formed under an electric field, is one process being explored to create rich microstructures. However, electrospinning a hydrogel system as it reacts requires an understanding of the gelation kinetics and corresponding rheology near the liquid-solid transition. In this study, we correlate the structure of electrospun fibers of a covalently cross-linked hydrogelator with the corresponding gelation transition and kinetics. Polyethylene oxide (PEO) is used as a carrier polymer in a chemically cross-linking poly(ethylene glycol)-high molecular weight heparin (PEG-HMWH) hydrogel. Using measurements of gelation kinetics from multiple particle tracking microrheology (MPT), we correlate the material rheology with the the formation of stable fibers. An equilibrated, cross-linked hydrogel is then spun and the PEO is dissolved. In both cases, microstructural features of the electrospun fibers are retained, confirming the covalent nature of the network. The ability to spin fibers of a cross-linking hydrogel system ultimately enables the engineering of materials and microstructural length scales suitable for biological applications.

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.

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 % .

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.

In vitro particulate analogue fluids for experimental studies of rheological and hemorheological behavior of glucose-rich RBC suspensions.

Suspensions of healthy and pathological red blood cells (RBC) flowing in microfluidic devices are frequently used to perform in vitro blood experiments for a better understanding of human microcirculation hemodynamic phenomena. This work reports the development of particulate viscoelastic analogue fluids able to mimic the rheological and hemorheological behavior of pathological RBC suspensions flowing in microfluidic systems. The pathological RBCs were obtained by an incubation of healthy RBCs at a high concentration of glucose, representing the pathological stage of hyperglycaemia in diabetic complications, and analyses of their deformability and aggregation were carried out. Overall, the developed in vitro analogue fluids were composed of a suspension of semi-rigid microbeads in a carrier viscoelastic fluid made of dextran 40 and xanthan gum. All suspensions of healthy and pathological RBCs, as well as their particulate analogue fluids, were extensively characterized in steady shear flow, as well as in small and large amplitude oscillatory shear flow. In addition, the well-known cell-free layer (CFL) phenomenon occurring in microchannels was investigated in detail to provide comparisons between healthy and pathological in vitro RBC suspensions and their corresponding analogue fluids at different volume concentrations (5% and 20%). The experimental results have shown a similar rheological behavior between the samples containing a suspension of pathological RBCs and the proposed analogue fluids. Moreover, this work shows that the particulate in vitro analogue fluids used have the ability to mimic well the CFL phenomenon occurring downstream of a microchannel contraction for pathological RBC suspensions. The proposed particulate fluids provide a more realistic behavior of the flow properties of suspended RBCs when compared with existing non-particulate blood analogues, and consequently, they are advantageous for detailed investigations of microcirculation.

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.

Viscoelasticity of blood and viscoelastic blood analogues for use in polydymethylsiloxane in vitro models of the circulatory system.

The non-Newtonian properties of blood are of great importance since they are closely related with incident cardiovascular diseases. A good understanding of the hemodynamics through the main vessels of the human circulatory system is thus fundamental in the detection and especially in the treatment of these diseases. Very often such studies take place in vitro for convenience and better flow control and these generally require blood analogue solutions that not only adequately mimic the viscoelastic properties of blood but also minimize undesirable optical distortions arising from vessel curvature that could interfere in flow visualizations or particle image velocimetry measurements. In this work, we present the viscoelastic moduli of whole human blood obtained by means of passive microrheology experiments. These results and existing shear and extensional rheological data for whole human blood in the literature enabled us to develop solutions with rheological behavior analogous to real whole blood and with a refractive index suited for PDMS (polydymethylsiloxane) micro- and milli-channels. In addition, these blood analogues can be modified in order to obtain a larger range of refractive indices from 1.38 to 1.43 to match the refractive index of several materials other than PDMS.