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Photonic and nAnomeTric High-sensitivity biO-Sensing

Periodic Reporting for period 3 - PATHOS (Photonic and nAnomeTric High-sensitivity biO-Sensing)

Reporting period: 2021-08-01 to 2022-11-30

Within the EU FET-OPEN H2020, the PATHOS consortium in 2019-2024 will plan to develop a radically new technology for the sensing of bio-systems and in-vivo diagnostics of biomedical conditions using hitherto unexploited tools (pioneered by the partners of this very interdisciplinary consortium): unconventional complex-system dynamical control and information sampling/processing, e.g. (i) magnetic-resonance imaging (MRI) and optically-detected magnetic-resonance (ODMR) sensing via cooling/suppression of thermal noisy background in-vivo, (ii) NMR intra-molecule/intra-tissue sensing and intra-cell NV-center thermometry, (iii) advanced sensing-data processing, including high-order correlation spectroscopy.
PATHOS will integrate the skills and facilities of 5 worldwide leading groups with complementary expertise in a multi-disciplinary consortium. PATHOS builds on recent ground-breaking results from its members resulted in publication of several publications including Nature group and patents, demonstrating skills ranging from theoretical physics to photonics, condensed matter and biophysics.
It is the purpose of PATHOS to pursue our potentially ground-breaking multidisciplinary effort in biomedical diagnostics. Starting from novel fundamental approaches to dynamical control, we seek to create new paradigms concerning control or guidance of spin evolutions in complex spin networks, so as to gear them to hitherto unforeseen MR applications in chemistry, biology and medicine. In a nutshell, PATHOS aims to further the very fruitful synergy pioneered by our partners towards developing new task-oriented comprehensive sensing strategies and exploring the new frontiers they entail for NMR, optical and MRI based analysis.
During the first reporting period of PATHOS, we have advanced as planned towards the expected long-term objectives. From the theory side, we have introduced conceptually novel approaches to the enhancement of heteronuclear spin-polarization transfer by means of repeated measurements, phase flips or spin-orientation flips for one of the spin species (alias the probe). Secondly, we have proposed new optics experiments for Zeno-based noise spectroscopy and studied several aspects of non-Markovian probes where the noise is correlated in time.
From the experimental side, we have constructed a widefield NV-based magnetic microscope, to form the basis for the experimental demonstrations in this project. We have initiated studies of enhanced magnetic sensing capabilities through compressed sensing techniques. We have developed novel schemes for controlling dense, interacting spin ensembles, through robust pulses relying on rapid adiabatic passage, as well as generalized sequences based on the icosahedral symmetry group. Besides, we have studied spin bath coupling through advanced noise spectroscopy schemes, achieving both efficient bath characterization using uneven echo sequences, as well as detailed spectroscopy with modulated, continuous control (the gDYSCO scheme).

During its second reporting period, at Weizmann we have found that the Anti-Zeno Effect (AZE) can lead to ≥500-fold reductions in the effective acquisition times in NMR experiments that are crucial for assigning protons in RNAs like those forming the genome of the SARS-CoV-2 viruses. In parallel, at HUJI we have developed and demonstrated enhanced magnetic and noise sensing using our diamond-based magnetic microscope, along with a novel optical scheme for radical concentration characterization. At INRIM we have completed the realization of an optical set up for quantum Zeno measurements (started during RP1). In addition, we have exploited our ODMR setup for magnetic sensing, showing 40 nT/Hz^1/2 magnetic sensitivity in continuous excitation and 70 nT/Hz^½ in biocompatible conditions. Furthermore, while at TUDO new dynamical decoupling (DD) pulse sequences have been proposed and experimentally tested in MRI systems, at UNIFI we have also started to develop other optimization methods based on Machine Learning (ML) methods, to predict the unknown noise spectrum avoiding the very large sets of DD measurements.

During its third reporting period, we have performed (at Weizmann) further experimental progress on the use of AZE to optimize heteronuclear polarization transfer in the presence of fast solvent chemical exchanges, demonstrating sensitivity-enhancing performance on RNA fragments derived from the SARS-CoV-2 genome. Novel 2D NMR techniques has been experimentally implemented it on murine brains in vivo at 15.2 T and ex vivo at 14.1 T. At HUJI we have further contributed to the use of NVs for enhanced sensing, aimed at using shallow NVs for thermal sensing and relaxometry in biological contexts. We have also studied advanced control techniques based on compressed sensing (CS) for improved sensitivity in ODMR. At INRIM, we have developed a dedicated setup for the simultaneous detection of neural cell activity and temperature NV sensing. Furthermore, we have published in Phys. Rev. Lett. a joint, involving INRIM, UNIFI and Weizmann, on Zeno-based photonic noise sensing. Another theoretical and experimental collaboration involving the same three PATHOS partners has led to another noise-sensing technique being able to unravel microscopic noise events affecting a continuous variable of a quantum system. At INRIM we have also demonstrated for the first time the detection of neural temperature variations (1 °C) associated with potentiation and inhibition of neuronal firing, by exploiting a nanoscale NV thermometer based on nanodiamond ODMR. Finally, at UNIFI, we have designed a new protocol of quantum pattern recognition, tested also on binary images of human blood vessel obtained from MRI (at TUDO).
The purpose of this consortium is first to propose new theoretical sensing schemes by using classical and quantum probes for electric and magnetic external fields, then to test them by using very diverse and complementary experimental platforms as optical setups, NV-centers, NMR, MRI and ODMR, and finally to find practical and robust future sensing applications in biomolecules and live tissues by creating new vestiges of chemical, biophysical and medical information that magnetic resonance can extract by exploiting our novel concepts. To this end, the best and most updated developments, expertise and creativity must be harnessed –in terms of dynamical control, data processing, magnetic resonance and photonics. Specifically, this project goes beyond the state-of-the-art in terms of cooling and control protocols, noise spectroscopy schemes and novel correlative measurements, to create a powerful toolbox with the potential of revolutionizing the biological studies and medical diagnostics. Achieving this goal requires creating a truly interdisciplinary interaction. The partners’ collaborative experience has taught us that although this could be extremely rewarding, the three communities that this project tries to bridge often speak in different languages on the same subjects. Therein lies the risk of this project, but we strongly believe that therein also lies its enormous potential. At its conclusion, we expect to fill the current gaps between the three communities, and thereby reap fruit that we believe will have a lasting impact on medical diagnostics.
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