The goal of this proposal is to allow observing and controlling ultrafast phenomena in a spatio-temporal window of 20fs-15nm at mid-IR by merging the extreme temporal resolution of the recently developed single-cycle mid-IR pulses with the spatial resolution of near field scattering optical microscope (aSNOM). The mid-infrared wavelength regime is of particular importance to materials science, chemistry, biology and condensed matter physics, as it covers the fundamental vibrational absorption bands of many gaseous molecules and bio-molecules. Adiabatic frequency conversion, a recent advance in nonlinear optics based on my PhD research and my current collaboration with MIT, generates ultrashort pulses in this important wavelength regime, which outperform the currently available mid-IR ultrashort sources, and unlike other techniques allows complete control of the temporal evolution by amplitude and phase manipulation of the NIR input. Combining these capabilities with aSNOM will allow one-of-a-kind route to perform active coherent control of quantum dynamics and allow single shot spatio-temporal observation of fast dynamical processes at nanoscale-resolution. Moreover, mid-IR ultrashort pulses delivered to the nanoscale can produce the high peak power needed to observe the nonlinear properties of the material under examination. Together with the richness of pulse shape manipulation it stands to enable, the currently impossible capability of intra-pulse multidimensional mid-IR spectroscopies at the nanoscale. This will open a gateway to all-optical, non-intrusive and label-free in situ studies of ultrafast processes in 2D materials and topological insulators, peptide evolution, photo-induced surface femtochemistry and protein folding. In particular, I plan to utilize these capabilities to explore nanoscale surface femtochemistry and to study energy pathways of hot carriers following the plasmonic decay in 2D materials and plasmonic nanostructures.

While the artificial design of pristine crystalline structures and the construction of dedicated periodic playgrounds for atoms and electrons in a solid have transformed our world, much is yet to be explored. I posit that the marvels of van der Waals polytypes should go much beyond and suggest that they offer a remarkable opportunity to rapidly, efficiently, and distinctively swap between numerous different crystals, symmetries, and dispersions at will. We have recently reported several new crystals made from identical 2D layers that differ only by their stacking symmetry. These perfectly commensurate and periodic di-atomic polytypes result in distinct electric potential steps and exclusive ladder-like polarizations owing to their various combinations of broken inversion and mirror symmetries. Our current research focus is mono-atomic polytypes that break both symmetries and offer further fundamental insight into the purely geometric impact of the atomic positions in the unit cell. Our preliminary experiments on graphitic polytypes detect novel internal polarizations, placing us in a great position to explore its interplay with superconductivity and orbital magnetization. The key challenge is to break the polytypes out of their commensurate meta-stable stacking and force the layers to slide at particular interfaces, only along armchair lattice orientation and for discrete inter-atomic distances. We have recently observed that such switching is possible using external electric fields, but only in the case of polar di-atomic bilayers. The swapping involves a thin incommensurate boundary wall encompassing a single stacking fault, which may slide rapidly in a super-lubric manner. Building on our ability to construct and distinguish adjacent polytypes, we aim to develop methods to efficiently switch between many distinctive polytypes and properties. With robust nano-meter and nano-second swapping capabilities, we envision ground-breaking SlideTronic technologies.

Understanding how the adaptive immune system works is of monumental scientific importance. It is remarkable, then, that despite the sophisticated modeling technologies available today, there are no human-relevant in vitro platforms mimicking the adaptive immune system in a physiological environment. Rather, state-of-the art models involve animals or in vitro systems that capture isolated elements of the immune response (e.g., activation by tumor cells). The challenge in developing immunized in vitro models is that adaptive immune cells cannot be co-cultured with non-autologous tissue, as they become activated and destroy it. We propose a groundbreaking paradigm that tackles this challenge, while advancing the greater ideal of personalized medicine. The approach builds on my expertise with the Organ-on-a-Chip: a microfluidic platform comprising human tissue that closely mimics organ functionality. I will create a novel platform integrating six vascularized Organ-Chips, all originating from iPSCs derived from a specific individual, which have been differentiated into specific tissue types. This fully isogenic platform will accommodate the donor’s adaptive immune cells: Because they originate from the same source, they will not be activated. Indeed, preliminary results support this hypothesis. The resultant system, Immune-Me-on-a-Chip, will constitute a first-of-its kind personalized-immunized-human platform for studying human physiology and biological threats. I will use the system to explore fundamental biological questions: (i) understanding how different isogenic and non-isogenic tissues interact with the immune system, e.g., in organ transplantation; and (ii) identifying how pathogens (antibiotic-resistant E. coli), as well as antibiotic treatment, affect human physiology and the immune response. This research will revolutionize the study of human physiology in general and of immunity in particular, and will open the door to a new era of personalized medicine.

NeuroNanotech will train eleven researchers to tackle one of the major challenges in Europe’s ageing population - neurological diseases. The ability to monitor and modulate neural activity using interfaces has enabled a better understanding of brain function and has led to therapeutic solutions for some neurological disorders. Yet, fundamental technological challenges, such as ensuring proper brain tissue interfacing and reliable long-term recording/stimulation after implantation, impede widespread clinical use. New approaches to provide effective treatments are urgently needed. NeuroNanotech will develop novel nanostructured flexible neural interfaces with highly improved tissue integration, minimizing foreign-body reactions and tissue scarring and allowing stable stimulation treatments. As main innovation, we will develop minimally invasive, ultra-sensitive spintronic magnetic sensors able to record stably without interfering with stimulation signals and avoiding electrode degradation. Connecting both interfaces, we will construct a low-invasive, closed-loop neurostimulation system that integrates feedback signals from the neural activity and provides real-time stimulation of the target structures according to the patient´s needs. To achieve these goals, NeuroNanotech brings together experts in nanotechnology, device engineering, neuroscience and clinical neurology. The individual research projects are highly interconnected, ensuring interdisciplinary training. Researchers will benefit from training in advanced research and relevant complementary skills, imparted by an international and intersectoral consortium of research institutes, universities, companies, hospitals and social organisations from 9 different countries. We will provide researchers a unique environment focused on innovation and collaboration, with a view to commercial applications of the research results. This framework will open researchers avenues in both academia and health-related industry.