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

Periodic Reporting for period 3 - MultiphysMicroCaps (Multiphysics study of the dynamics, resistance and targeted therapy potential of deformable Micro-Capsules)

Reporting period: 2021-06-01 to 2022-11-30

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 30 months, we have made great progress on all the workpackages of the project:

- WP1: Advanced numerical modelling strategies to simulate a deformable microcapsule in an external flow.
1. We have studied the effect of the membrane finite thickness (PhD of X.Y. Wang recruited through the CSC program, Dr. C. Dupont post-doctorate funded on the ERC project) in collaboration with Prof D. Barthès-Biesel (BMBI, UTC), Prof P. Le Tallec (Ecole Polytechnique) and Dr. M. Vidrascu (INRIA Paris). We have developed a fluid-structure interaction model modeling the capsule wall with thin-shell finite elements and accounted for any non-linear constitutive law.
2. In collaboration with Prof J.M. Fullana, we have developed a Volume of fluid – Shell Finite Element code to account for finite inertial effects in the fluid flows. We have studied the relaxation of microcapsules in confined environments.
3. We have unraveled interesting results on the interaction of microcapsules.
a. Thanks to the venue of Prof X.Q. Hu from Hunan University as Visiting Fellow for 1 year (funded by the CSC program), we have discovered a new mode of interaction of microcapsules in flow with the formation of doublets. Prof Hu will come back for 2 years (2021-2023) with funding from the Hauts-de-France region.
b. In collaboration with Prof Y. Sui (QMUL), we have studied the flow of trains of microcapsules in a bifurcated channel (PhD of R.X. Lu, QMUL) and how they interact. We used the lattice-Boltzmann method to model the fluid flows inside and outside the capsule and accounted for inertial effects.

- WP2: Numerical modelling of capsule damage and rupture
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 N. Grandmaison, funded by a fellowship from Ecole Normale Supérieure). We have implemented the damage model in the boundary integral – finite element code and studied the damage processes induced by the deformation of the capsule giving rise to rupture.
We are currently developing a new approach to include the modeling of rupture in the fluid-structure interaction model (PhD of C. El Mertahi, funded on the ERC project).

- WP3: Development of reduced-order models
In collaboration with Profs P. Villon (Roberval, UTC) and F. de Vuyst (LMAC, UTC), we have developed data-driven reduced modelling strategies to circumvent the long computational times that result from solving the 3D capsule-flow interactions (PhD of T. Boubehziz, postdoctorate of Dr. C. Dupont, funded on the ERC project). We have shown their great precision and are working on new dynamic models.

- WP4: Characterization of microcapsule resistance
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 Dr. A. 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 (internships of E. Decombis, M. Segrestin).
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. Our objective is to use microfluidic strategies to sort them based on their mechanical properties and use the latter as a biomarker of inflammation. We have validated microsystem design on microcapsules and then focused on lymphocytes (white blood cells), which are known to change their mechanical properties in case of inflammation.

- WP5: Application to antioxidant encapsulation
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). We have fabricated and characterized different batches of microcapsules, and created in vitro models of digestion to test how the external fluid conditions (pH, enzymes, …) affected the release of the encapsulated antioxidant. In vivo tests have been conducted in Unilasalle Beauvais through a collaboration with P. Anton-Gay.
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.