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Multiphysics study of the dynamics, resistance and targeted therapy potential of deformable Micro-Capsules

Periodic Reporting for period 1 - MultiphysMicroCaps (Multiphysics study of the dynamics, resistance and targeted therapy potential of deformable Micro-Capsules)

Reporting period: 2018-06-01 to 2019-11-30

Encapsulation consists in enclosing an internal medium in a solid semi-permeable membrane to protect it and control the exchanges with the environment. Being at the source of innovative applications in the fields of biotechnologies, pharmacology, energy storage and food industry, capsules offer tremendous potential in the process engineering world. But scientific challenges remain to be met, such as finding the optimal compromise between payload and membrane thickness, characterizing the membrane resistance and controlling the moment of rupture.
The project explores the use of deformable liquid-core capsules of micrometric size to efficiently transport active material, with a primary focus on health-related applications. We will design innovative sophisticated numerical models and high-tech experiments, needed to determine the potential of such vectors for the protection of active substances, predict membrane breakup to control the delivery, and optimize their properties for specific industrial and biomedical applications. The project will, for the first time, study the effect of a finite wall thickness on the dynamics of elastic microcapsules, propose advanced modelling approaches and microfluidic experiments of their deformability and breakup under hydrodynamic stresses, account for the inherent size variability of given capsule populations, and introduce reduced-order models to facilitate real-time simulations. As a specific application, we will study the potential of liquid-core microcapsules to encapsulate antioxidants for food enrichment.
Over the last 18 months, we have made great progress on all the workpackages of the project:
- WP1: We have worked on the development of advanced numerical modelling strategies to simulate a deformable microcapsule in an external flow and study the effect of the membrane finite thickness (PhD of Xingyi Wang, that we have recruited through the CSC program). Thick-shell finite elements have been developed in collaboration with Profs D. Barthès-Biesel (BMBI, UTC), P. Le Tallec (Ecole Polytechnique) and M. Vidrascu (INRIA Paris). In collaboration with Prof J.M. Fullana, we have worked on a Volume of fluid – Shell Finite Element code.
We have also unraveled interesting results on the interaction of microcapsules. Thanks to the venue of Prof X.Q. Hu from Hunan University as Visiting Fellow for 1 year, we have discovered a new mode of interaction of microcapsules in flow, in which they can form doublets. In collaboration with Prof Y. Sui and R.X. Lu (QMUL), we are studying the flow of trains of microcapsules in bifurcated channel.
- WP2: In collaboration with Prof D. Brancherie (Roberval, UTC), we have developed the very first numerical model accounting for the damage mechanisms that may occur when a microcapsule is subjected to an external flow worked (PhD of Nicolas Grandmaison, that we have recruited thanks to an Ecole Normale Supérieure fellowship). It is allowing us to predict when rupture occurs upon the deformation of the capsule.
- WP3: In collaboration with Profs P. Villon (Roberval) and F. de Vuyst (LMAC, UTC), we have developed reduced modelling strategies based on the Proper Orthogonal Decomposition and Diffuse Approximation methods, to circumvent the long computational times that result from solving the 3D capsule-flow interactions (PhD of Toufik Boubehziz, who was recruited on the ERC). We have shown their great precision and are working on new dynamic models.
- WP4: We have built an experimental platform capable of measuring with precision the deformation of deformable microcapsules in flow and of identifying their mechanical resistance (purchase of a microfluidic flow bench, profilometer, counter-rotating rheometer, creation of a micro-compressor test bench). We have worked on the fabrication of microcapsules and of flat discoidal models of the membrane by interfacial reticulation of a proteic solution, and on the study of their properties (Postdoctorate of Adlan Merlo, who was recruited on the ERC).
In collaboration with Drs A. Le Goff and B. Kaoui (BMBI, UTC), we are developing a microfluidic technique to study the rupture of microcapsules by trapping them at a constriction (internship of Emma Decombis).
In collaboration with Drs C. Védrine and Y. Bounab (Biological Microsystems and Advanced Optics Engineering unit, Bioaster) and A. Le Goff (UTC), we have finally studied how to apply some of our microfluidic devices to cells. We have focused on lymphocytes (white blood cells), which are known to change their mechanical properties in case of inflammation. Our objective is to use microfluidic strategies to sort them based on their mechanical properties and use the latter as a biomarker of inflammation.
- WP5: In collaboration with Profs C. Rossi and A. Cordin (GEC, UTC), we have developed microencapsulation techniques to encapsulate antioxidants and circumvent their very low natural stability. We have focused on an antioxidant extracted from a local crop, the beetroot, and studied which encapsulating material allows to protect it from the enzymes and pH of the stomach and allows the antioxidant to be released in the small intestine (PhD of Nesrine Ben Hadj Youssef, funded by Hauts-de-France – project CapsAntiOx 2016-2020).
In terms of publications, two manuscripts are under review (WP1 and WP3), and five others are in the process of being finalized linked to WP1, WP2, WP3, WP4 and WP5.
The project outcomes will be (i) new advanced three-dimensional numerical models of the fluid-structure interactions and rupture of a microcapsule, accounting for a finite wall thickness, (ii) microcapsule optimization tools based on reduced-order models, (iii) microscopic techniques to measure the capsule mechanical properties, and (iv) an applied study of optimization of antioxidant encapsulation in microcapsules.