Dominique Barthes-Biesel

Influence of bending resistance on the dynamics of a spherical capsule in shear flow

The objective of the paper is to study the effect of wall bending resistance on the motion of an initially spherical capsule freely suspended in shear flow. We consider a capsule with a given thickness made of a three–dimensional homogeneous elastic material. A numerical method is used to model the fluid–structure interactions cou- pling a boundary integral method for the fluids with a shell finite element method for the capsule envelope. For a given wall material, the capsule deformability strongly decreases when the wall bending resistance increases. But, if one expresses the same results as a function of the two–dimensional mechanical properties of the mid–surface, which is how the capsule wall is modeled in the thin–shell model, the capsule deformed shape is identical to the one predicted for a capsule devoid of bending resistance. The bending rigidity is found to have a negligible influence on the overall deformation of an initially spherical capsule, which therefore depends only on the elastic stretching of the mid–surface. Still, the bending resistance of the wall must be accounted for to model the buckling phenomenon, which is observed locally at low flow strength. We show that the wrinkle wavelength is only a function of the wall bending resistance and provide the correlation law. Such results can then be used to infer values of the bending modulus and wall thickness from experiments on spherical capsules in simple shear flow.

Polymerization kinetics of n-butyl cyanoacrylate glues used for vascular embolization.

Vascular embolization is a minimally invasive treatment used for the management of vascular malformations and tumors. It is carried out under X-ray by navigating a microcatheter into the targeted blood vessel, through which embolic agents are delivered to occlude the vessels. Cyanoacrylate liquid glues have been widely used for vascular embolization owing to their low viscosity, rapid polymerization/solidification rate, good penetration ability and low tissue toxicity. The objective of this study is to quantitatively investigate the physical properties of two n-butyl cyanoacrylate (nBCA) glues (Glubran 2 and Histoacryl) mixed with an iodized oil (Lipiodol) at various concentrations. We show that an homogeneous solution results from the mixing of the glue and Lipiodol, and that the viscosity, density and interfacial tension of the mixture increase with the proportion in Lipiodol. We have designed a new experimental setup to systemically characterize the polymerization kinetics of a glue mixture upon contact with an ionic solution. We observe that the whole polymerization process includes two phases: an interfacial polymerization that takes place at the interface as soon as the two liquids are in contact with a characteristic time scale of the order of the minute; a volumetric polymerization during which a reaction front propagates within the mixture bulk with a characteristic time scale of the order of tens of minutes. The polymerization rate, front propagation speed and volume reduction increase with the glue concentrations. It is the first time that such comprehensive results are obtained on liquid embolic agents.

Transient behavior and relaxation of microcapsules with a cross-linked human serum albumin membrane

Capsules consist of droplets enclosed by a membrane with shear resistant properties especially when fabricated by interfacial cross-linking. In many applications, the protection and release of the internal medium need to be strictly controlled. It is possible to tune the membrane mechanical properties by changing the physico-chemical conditions of the fabrication process, but a good control of the production requires their characterization, which is a scientific challenge, since the objects are a few tens of microns in size at most. One advantageous approach is to resort to microfluidic techniques. We study the transient response of capsules having a cross-linked human serum albumin (HSA) membrane, as they flow through a sudden expansion. We determine the characteristic time scales of the capsule relaxation and compare them to the ones predicted by a full numerical model of the relaxation of a capsule flowing in a rectangular channel, for which the membrane is assumed to be purely elastic. We show that the membrane is viscoelastic and that the relaxation is solely a function of the ratio of the relaxation time to the convective time.

Characterization of the mechanical properties of cross-linked serum albumin microcapsules: effect of size and protein concentration

A microfluidic technique is used to characterize the mechanical behavior of capsules that are produced in a two-step process: first, an emulsification step to form droplets, followed by a cross-linking step to encapsulate the droplets within a thin membrane composed of cross-linked proteins. The objective is to study the influence of the capsule size and protein concentration on the membrane mechanical properties. The microcapsules are fabricated by cross-linking of human serum albumin (HSA) with concentrations from 15 to 35 % (w/v). A wide range of capsule radii (∼40–450 μm) is obtained by varying the stirring speed in the emulsification step. For each stirring speed, a low threshold value in protein concentration is found, below which no coherent capsules could be produced. The smaller the stirring speed, the lower the concentration can be. Increasing the concentration from the threshold value and considering capsules of a given size, we show that the surface shear modulus of the membrane increases with the concentration following a sigmoidal curve. The increase in mechanical resistance reveals a higher degree of cross-linking in the membrane. Varying the stirring speed, we find that the surface shear modulus strongly increases with the capsule radius: its increase is two orders of magnitude larger than the increase in size for the capsules under consideration. It demonstrates that the cross-linking reaction is a function of the emulsion size distribution and that capsules produced in batch through emulsification processes inherently have a distribution in mechanical resistance.

Polymerization kinetics of a mixture of Lipiodol and Glubran 2 cyanoacrylate glue upon contact with a proteinaceous solution

The Glubran 2 cyanoacrylate glue is a liquid embolic agent used to block blood vessels endovascularly. Typically mixed with an iodized oil (Lipiodol) for visualization under X-ray, it polymerizes when in contact with blood and tissues owing to the presence of ions and proteins. The objective of the study is to determine the influence of plasma proteins in the polymerization reaction. A triggering solution containing bovine serum albumin (BSA) and the main blood ions is used as a model of plasma. The polymerization kinetics of Glubran 2-Lipiodol mixtures is measured upon aspiration in a capillary tube and contact with the proteinaceous solution. Having varied the glue and protein concentrations, we show that glue-Lipiodol mixtures with concentrations larger or equal to 25% polymerize when put in contact with an ionic solution containing at least 4% of BSA. The reaction is decomposed into two phases: a fast zwitterionic polymerization induced by the BSA molecules followed by a slower polymerization phase. The reaction speed and extent of the solidification region mostly depend on the glue concentration. The time for the glue solution to polymerize over a 1mm thickness varies from 5s for pure glue to about 1min for a 50% glue concentration, and 10min for a 25% glue mixture. It is the first time that the kinetics of the two polymerization reactions is quantified for Glubran 2, which will provide the information needed by interventional radiologists to optimize the planning of endovascular glue injection.

Therapeutic Embolization by Cyanoacrylate Liquid Glues Mixed with Oil Contrast Agent: Time Evolution of the Liquid Emboli

Glue embolization is a minimally invasive treatment used to block the blood flow to specific targeted sites. Cyanoacrylate liquid glues, mixed with radiopaque iodized oil, have been widely used for vascular embolization owing to their low viscosity, rapid polymerization rate, good penetration ability and low tissue toxicity. In this study, we have conducted an in vitro study to quantitatively investigate the polymerization kinetics of two n-butyl cyanoacrylate (nBCA) glues (Glubran 2 and Histoacryl) mixed with an iodized oil (Lipiodol) at various concentrations. The polymerization process of the glue-oil mixture is systematically characterized upon contact with a protein ionic solution mimicking plasma and compared to the case without protein. The results provide essential information for interventional radiologists to help them understand the glue behavior upon injection, and thus control embolization.