In order to achieve the project goals the HYPERDIAMOND consortium has structured the work to be undertaken in three scientific-technical work packages for establishing the enabling technologies, two innovation focused work packages for bridging the gap to technological innovation, a preclinical imaging work package for proof of concept experiments, and a benchmarking work package for final assessment of the produced results. One work package for project management and administration and one work package dedicated to the dissemination and exploitation of the project results are framing the overall work plan.

Work Plan Project h2020

 

The main goal will be the continued development of experimental setups and initial proof of concept experiments for diamond-based polarization, achieving high maximal polarization and high polarization throughput. This will be conducted in close collaboration with theoretical modelling, simulations and optimization.

The WP will focus on nanodiamond material science aspects: optimizing NDs for imaging (enhancing relaxation time, narrow size distribution, enlarging the NV centre and 13C concentration) and as the diamond basis for the Diamond Hyperpolarizer (small nanodiamonds with long NV centre coherence times). It will compare and optimize two key processes for HPHT ND production – milling of large diamonds and a direct conversion  of organic substances (containing C, H and F atoms) into nano- and microdiamonds (ND and MD).

The main goal of this work package is the functionalization and coating of NDs – serving as a platform for attachment of biomolecules and tuning of in vivo behaviour. The ND-probes will be functionalized with several selected biomolecules (e.g. monoclonal antibodies), for which the process will then be up-scaled, and designed for easy medical use. The biocompatibility and toxicity studies of the NDs for initial imaging experiments will also be performed in this work package.

The main goal is the development of the Diamond Hyperpolarizer. First, an initial hyperpolarization system based on existing infrastructure will be developed.  Second, prototype versions of the Diamond Hyperpolarizer will be developed and installed, incorporating a tailor-made permanent magnet system. Finally, a developed fully-functional prototype version would provide a turnkey solution for use by medical researchers world-wide.

The key proof-of concept MRI and MRS experiments will be performed in this workpackage, including: 1) Initial proof of concept for hyperpolarized MRI imaging for both technologies, 2) Initial tumour imaging in ovo (chicken eggs) using the ND-probes, 3) Metabolic imaging in a biological sample via hyperpolarized ¹³C-pyruvate and novel metabolites (e.g. ¹³C-Glucose) using the Diamond Hyperpolarizer.

The main goal is the industrial up-scaling from a typical milligram scale in research and development to a gram scale to ensure availability of functionalized NDs for future needs. The focus for WP6 is on a reproducible, economic, and ecological production process. Respective production lots for functionalized ND will be carried out. As a long-term goal the commercial availability of functionalized NDs shall be established, to enable diagnostic field tests and to make functionalized NDs available to a wide range of applications.

We will perform initial benchmarking and in vivo assessment of the developed technologies. Comparative studies will be performed with a commercial dissolution-DNP polarizer and with PET imaging. In addition, the efficacy of ND-probes and small-molecules produced in the HYPERDIAMOND project will be assessed in vivo, for different tumour and inflammatory model. Finally, we will perform in vitro biocompatibility, acute toxicity and bio-distribution assessment of the optimized ND-probes. Working closely with WP3, we will achieve rapid feedback loops for the optimization of the functionalized NDs.

The main goal is to assure for the entire duration of the project that results are widely communicated across the scientific and clinical community, that clinical practitioners become aware of the new polarization system, and that it will prepare the commercial exploitation of the polarization system first for the clinical market and later – requiring more stringent certification – in clinical diagnostics.

The project management is led by UULM and supported by ARTTIC and will implement a result driven management approach ensuring project progress towards the agreed milestones and objectives, as well as contractual deliverables and obligations.