Intratumor heterogeneity is a major challenge preventing the wide-spread adaptation of a personalized medicine. The objective of this proposal is to develop a complementary set of beyond state-of-the-art, nanotechnology-driven tools for effective diagnostics of intratumor heterogeneity and subsequent therapy with tailored nanoparticles. The methods include (i) collection of molecular biopsies at improved spatial resolution (~100 µm) by tissue permeabilisation with electroporation, (ii) automation of sample preparation on electroporated extracts (RNA and proteins extraction) using centrifugal microfluidics and (iii) application of therapeutic gold and silica nanoparticles addressing the tumor subclonality. The hypothesis behind the MATISSE project is that the combination of the proposed technologies will for the first time enable dissecting molecular cartography and heterogeneity of solid tumours addressable by nanoparticle drugs. To test the hypothesis, international consortium of experts in engineering, nanotechnology, medicine, biochemistry, and machine learning will jointly tackle the following specific challenges: 1) development of a novel e-biopsy device for molecular harvesting in vivo; 2) determination of the electric pulse parameters for RNA and protein extraction from tumour model in mice and excised human skin and internal tumours; 3) development of a microfluidic technology for interfacing e-biopsy devices and laboratory instrumentation that ensures integrity of data collection during biopsies analysis; 4) development of nanoparticles combinations to address the heterogeneity of the 4T1 model tested in vivo. The project involves partners from 4 countries (Project leader: Tel Aviv University). SINTEF will focus on the development of a centrifugal microfluidic device for automation of sample preparation (RNA and protein extraction), interfacing of e-biopsy devices with other instrumentation to ensure integrity of data collection during biopsies analysis.
Project leader: Elizaveta Vereshchagina
Category: Teknisk-industrielle institutter
Institution: SINTEF DIGITAL