Leader: Ecole Polytechnique Fédérale de Lausanne, Institute of Materials, Powder Technology Laboratory
In WP 1, “Particle coating and functionalisation and novel equipment for coating and separation”, methods for reproducible coating and derivatisation of SPION with molecular species detected and determined by WP 3a and WP 3b will be developed. An additional objective is that these particles have to be biocompatible and colloidally stable in different biological environments like synovial fluid, intra- or extracellular fluids, and also in blood and urine. The derivatisation of the particles is strongly linked with equipment development for coating and separation. The objective is to develop equipment which enables the efficient, cheap, and reproducible coating and separation at lab as well as pilot production scale. Additionaly, the development of small micro-fluidic based equipments which allow on-demand coatings are foreseen.
As preliminary results indicate, polyvinylalcohol(PVA)-coated iron oxide particles are taken up by macrophages and monocytes and synovial lining cells. EPFL will prepare batches of well-characterized PVA-coated particles using established methods. In a second step (and depending of the results obtained in WP 2), the coating of the particles will be optimized so that uptake efficiency and inflammation detection is maximal.
It was shown that SPION that are targeted to specific organelles and magnetically separated afterwards show a very specific profile of adsorbed cell proteins. Based on this, EPFL and the University of Fribourg will develop in cooperation with WP 3 specifically functionalised SPION which allow the adsorption or binding of potential biomarkers or several proteins which can be used as biomarkers (protein profiling). This part of the project comprises various important tasks like controlled and reproducible multiple surface derivatization of the particles, the thorough analytical analysis of the thus created surfaces, and the guaranteed colloidal stability of the final product.
Before the functionalised particles are used for in-vivo tests, the particles will be used for detection of biomarkers in urine, serum, or if necessary in synovial liquid. EPFL will develop for each type of fluid a coating of the particles which prevents uncontrolled agglomeration of the particles during use. Additionally, the particles have to show a very high specific ability to adsorb or bind specific antibodies. Finally, the particles must permit a fast and quantitative magnetic separation step for further analysis of the adsorbed protein or detection in a bioassay.