Metrology for innovative nanotherapeutics
LNE coordinates the project (WP6 leader), lead the WP3 and support the ETPN in the dissemination, exploitation and communication tasks (WP5). The project coordinator brings her 8 years’ experience in regulatory science and pre-clinical characterisation of nanomedicines and in managing nanomedicine and medical devices dedicated infrastructures. LNE propose the use of A4F-UV and fraction collection, for the separation of nanotherapeutics from biological matrices, hybrid SEM-AFM metrology for sizing and identification and SC-ICP MS for the detection of inorganic NPs in cells and tissues.
BAM leads WP1 and will further contribute to the technical WP2, WP3, and WP4 with its traceable optical characterisation methods and validated analytical methods for functional group quantification.hosts a unique collection of analytical and physicochemical methods for the material characterisation and is a world-wide known producer of reference materials including NPs. BAM division Biophotonic has world leading capabilities in absolute fluorometry, year-long expertise in the syntheses and surface modification of different types of inorganic nanomaterials, has produced more than 20 certified fluorescence standards, and is involved in standardisation activities of ISO 229 and IEC/TC113.
INRIM brings its experience in many metrological fields including the development of advanced microscopy technologies, biochemical analysis, micro/nanomaterial characterisation and biological samples production and characterisation. INRIM has resources, infrastructures (CARS/SRS/TPEF microscopy, widefield fluorescence microscopy, atomic force microscopy (AFM), biological laboratories and genetic real-time PCR and digital-PCR measurement capabilities) and expertise on spectroscopic and microscopic techniques that will be used to characterise NPs in tissue phantoms and living biological tissues in WP4 (WP leader).
PTB has world-leading capabilities in its own laboratory at the synchrotron radiation facility BESSY II in Berlin. The PTB X-ray radiometry working group has established methods for traceable characterisation of NPs (SAXS, wide angle X-ray scattering -WAXS, analytical centrifugation, μCT), provides test and calibration services, is involved in standardisation activities and leads WP2. With its synchrotron-based characterisation methods, PTB further contributes to the technical WPs 3 and 4.
RISE provides expertise and instrumentation for structural and chemical analysis of individual nanoparticles in their aqueous environment using advanced cryo-preparation techniques and analyses by cryo-TEM and cryo‑ToF-SIMS. Freeze-drying methods that will allow for analysis of nanoparticle samples with vacuum-based techniques (such as X-ray photoelectron spectroscopy-XPS) will be developed and evaluated with respect to structural and chemical integrity of the lipid nanoparticles. The homogeneity of organic coatings on inorganic nanoparticles will be determined on a particle-to-particle basis (WP2) and 3D distributions of inorganic and lipid nanoparticles in tissues and tissue phantoms will be measured (WP4).
SMD brings expertise in dimensional characterisation by multidetector and hyphenated approaches, especially with AF4 coupled to various optical detectors (UV-VIS absorption, Multi angle light scattering-MALS, dynamic light scattering-DLS). This is supported by deep understanding of the physics of the instrumentation and advanced statistical tools, in order to provide more accurate results and with precision properly estimated. SMD will strongly be involved in WP3 and in WP2 for dimensional characterisation.
CEA has a strong expertise on the manipulation and characterisation of nanomaterials issued from different field of applications or from fundamental research studies, including nanomaterials related to biological or medicine field. CEA is also recognised for its expertise in small angle X-ray scattering (measure, analysis, traceability, static and in situ studies). CEA Lions has participated to several European project (recently in the field of metrology (EURAMET Nanogenotox 2008-2013, EMPIR Innanopart 2014-2018, EMPIR NpSize 2018‑2021) or nanosafety (Harmless 2021-2025)). Taking benefit of its different field of expertise, the CEA participates to the development of traceable methodologies for measuring particle size and concentration of nanoparticles in the WP2.
Curadigm brings its expertise in the design, synthesis and characterisation of lipid-based nanoparticles including liposomes and Lipid Nanoparticles. In the WP1 Curadigm will provide different lipid-based nanomaterials that will be used for methods development in WP2 and 4. Curadigm has also a strong expertise in preclinical evaluation on nanotechnologies supporting activities of WP4. Curadigm will ensure in its in-vivo facilities the injection of the different materials from the project in biological tissues and in animals (mouse model) to support activities of biological measurement in biological medium.
ETPN has been acting as the official think tank of Nanomedicine in Europe for the last 15 years, shaping an active community of more than 125 stakeholders from 27 European countries notably including academia, SMEs, industry, healthcare providers and national associations. It organises their common strategic thinking for the future of medical applications of nanotechnologies and foster the clinical translation of the best Nanomedicine innovations born in Europe. In MetrINo, the ETPN will coordinate as WP5 leader the Communication, Dissemination and Exploitation activities, with the clear goal to optimise the impact of the Project for the nanomedical, industrial and metrological communities during and after its granted period.
Nanobiotix brings its expertise in the design, synthesis and characterisation of HfO2 nanoparticles. In the WP1, Nanobiotix will provide different HfO2 nanoparticles with a size < 10 nm and a size > 10 nm and different surface coatings. In WP2, Nanobiotix will also investigate the storage and long- term stability of the HfO2 NPs in various aqueous microenvironments and biologically compatible buffers.
The OGSA hospital cooperate with INRIM in studies focused on the development of innovative microscopy techniques to determine the kinetics of lipid-based nanoparticles uptake in pellets of chondrocytes or slices of cartilage. It provides link to clinicians (including orthopaedic surgeons), allowing also the constant supply of patient-derived biopsies used for the preparation of explants and primary cells. This will allow OGSA to collect surgical waste human cartilage from hip, knee or disc suitable to prepare slices, to isolate and expand chondrocytes and to establish 3D cultures with the isolated chondrocytes.
OVGU brings in its unique expertise in translational biomedicine to fabricate 3D tissue engineered biological samples and 2D cell cultures in WP4. With its strong research focus in tissue engineering and NP treatment, it will further provide information for the development of time- and concentration-dependent spiking protocols with high relevance for the future clinical applications of NPs in diagnostics and therapy and for the interlaboratory comparison (WP4). Moreover, with our strong medical imaging background, will contribute with its unique benchtop X-ray fluorescence computed tomography imaging modality for localization, quantification and dynamic tracking of NPs in tissues and phantoms (WP4).
UGent brings world-leading expertise in the development of methods for the determination, speciation and isotopic analysis of (trace) elements via ICP-MS and their application in challenging interdisciplinary contexts. It has a longstanding interest in solving real-world problems in biomedical and clinical contexts. The group will bring its extensive experience in the context of single particle/cell and laser ablation ICP-MS for the detection of NPs incorporated in biological tissues (WP4).
UniPv provides a unique range of expertise for the advanced characterisation of nanomaterials relevant to WP2, including strategies for quantitative analysis of organic coatings on MONPs combining thermos‑gravimetric analysis, differential scanning calorimetry, SEM-EDX, Raman and mass spectroscopies techniques. For morphological characterisation of lipid-based NPs, UniPV will implement cryo-TEM and fluorescence analysis methods. UniPV will also contribute to WP4 with Raman micro-spectroscopy and fluorescence microscopy tools, as well as to WP3 and inter-lab studies in WP5 with FFF expertise.
Empa Two laboratories of Empa will contribute to the project. The particles-biology interactions laboratory has an in-depth knowhow and experience with various in-vitro assays, build up a profound experience with various imaging technologies (optical microscopy, analytical electron microscopy (SEM, TEM combined with EDX spectroscopy), Raman spectroscopy etc.) for the characterisation of different types of NP particles in cells and tissues. The team is very active in developing correlative approaches for obtaining complementary information about the interaction of the NPs and the biological environ-ment. Furthermore, the laboratory uses ICP-OES/MS on a routine basis to characterize NP composi-tion and to assess NP concentration in cells and tissues. The second Empa laboratory, the Center for X-ray Analytics, investigates NP size, shape, agglomeration and self-assembly behaviour investigating more specifically NP interactions in protein environments using different techniques, such as SAXS, WAXS, X-ray imaging (CT) and SANS. Their approach to investigate the dynamics of the NP protein corona building dynamics is unique and provides a profound insight into this essential topic. Empa is already used to handle the RDM and DMP of HE projects.
LGC brings world-leading expertise in development of traceable methods for nanomaterial characterisation (spICP-MS), hyphenated approaches (FFF coupled to PTA, MALS, DLS, ICP-MS with off-line TEM/EDX), sample preparation strategies, reference materials production as well as provision of test and calibration services, and will lead WP3. With a strong focus on metrology and long-track record developing reliable element quantitation approaches with e.g., LA/ICP-MS, LGC will also support other technical WP2.
NPL brings world-leading expertise in the measurement of nanoparticles with a suite of methods for the characterisation in liquids (DLS, PTA, TRPA, surface NMR and analytical centrifugation), as well as quantitative chemical analysis by XPS (WP2). This is complemented by non-linear optical microscopy capability and expertise for the label free measurement of particle distribution in complex (e.g. biological) matrices (WP4). NPL contribute to the development of documentary standards within CEN, ISO and ASTM and has an established track record of successfully delivered international interlaboratory comparisons (WP5).