THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

Cancer represents one of the major challenges for modern medicine as we still lack tools to selectively target malignant over healthy tissues. The main issues with state of the art anti-cancer treatments lie on their inefficiency and their associated side-effects. Improving this treatments has focused a lot of attention of the scientific community and has led to the development of new strategies. Harnessing our own immune system to fight malignant cells is one of the strategies with promising potential to improve cancer treatments, although challenges still remain. An emerging therapeutic modality to trigger our immune system against carcinogenic tissues are bispecific antibodies (bsAbs). bsAbs are the combination of two antigen binding specificities on a common scaffold. The potential of these constructs to bind to two antigens can be used to simultaneously target cancer cells and the immune cell which will effectively kill it. The problem of bsAbs is their slow and tedious production process, which is responsible for their linear development. Herein we propose a methodology to speed up and improve the efficiency of their production. Our approach will consist in using novel site-specific bioorthogonal ligation reactions to tag monoclonal antibodies (mAbs) with linkers that will serve as substrates for an inverse electron demand Diels Alder condensation. By condensation of different combinations of tagged mAbs a library of bsAbs will be assembled. The immunondulatory properties of the bsAbs will be tested in high throughput using a high content imaging platform. We will be able to select potential bsAbs for anticancer treatment from our extense library which will study in more depth using classic immunology methods to determine their mode of action and their anti tumour efficacy. The acceleration of both the synthesis and identification of relevant bsAbs for anticancer treatments would significantly increase the presence and value of this technology.

Over the past decades, significant advances have been achieved in the performance of Li-ion batteries by the development of new active materials and better understanding of energy storage and degradation mechanisms. One aspect of batteries that has received little attention so far, is the form factor of the electrodes. However, simple changes in the battery architecture, such as increasing the coating thickness, allows to drastically decrease the relative fraction of dead volume in the battery (e.g. separators and current collectors). Theoretically, it is possible to replace a stack of ten standard 50 µm thick electrode coatings by one 500 µm thick coating. This would result in up to 30% savings in weight as well as volume of the battery, and would be transformative for both portable electronics and electrical vehicles. However, this is fundamentally challenging because of 1) slow ion diffusion through thick electrodes, 2) high electric resistance through the thickness of the electrode, and 3) cracking and flaking challenges during the fabrication of thick electrodes. This MSCA Fellowship is building on novel gel electrodes developed by the applicant, which can be moulded into 3D geometries that allow to move away from the current flat battery morphology and to address the above challenges with thick battery electrodes. During this Fellowship, the dynamics of ion and electron transport in thick 3D interdigitated electrodes will first be simulated. Then, the electrochemical performance of the gels will be optimised, in particular, a phase separation method to improve Li-diffusion will be optimised. Next, the thermal moulding process will be optimised to create interdigitated electrodes which will be tested in half and full cells. Finally, the proposed fabrication process will be demonstrated on a roll-to-roll coater, which is important to prove its scalability to industrial stakeholders.

Cooling is essential for food and drinks, medicine, electronics and thermal comfort. Thermal changes due to pressure-driven phase transitions in fluids have long been used in vapour compression systems to achieve continuous refrigeration and air conditioning, but their energy efficiency is relatively low, and the working fluids that are employed harm the environment when released to the atmosphere. More recently, the discovery of large thermal changes due to pressure-driven phase transitions in magnetic solids has led to suggestions for environmentally friendly solid-state cooling applications. However, for this new cooling technology to succeed, it is still necessary to find suitable barocaloric (BC) materials that satisfy the demanding requirements set by applications, namely very large thermal changes in inexpensive materials that occur near room temperature in response to small applied pressures. I aim to develop new BC materials by exploiting phase transitions in non-magnetic solids whose structural and thermal properties are strongly coupled, namely ferroelectric salts, molecular crystals and hybrid materials. These materials are normally made from cheap abundant elements, and display very large latent heats and volume changes at structural phase transitions, which make them ideal candidates to exhibit extremely large BC effects that outperform those observed in state-of-the-art BC magnetic materials, and that match applications. My unique approach combines: i) materials science to identify materials with outstanding BC performance, ii) advanced experimental techniques to explore and exploit these novel materials, iii) materials engineering to create new composite materials with enhanced BC properties, and iv) fabrication of BC devices, using insight gained from modelling of materials and device parameters. If successful, my ambitious strategy will culminate in revolutionary solid-state cooling devices that are environmentally friendly and energy efficient.