Periodic Reporting for period 4 - PATHOS (Photonic and nAnomeTric High-sensitivity biO-Sensing)
Reporting period: 2022-12-01 to 2024-03-31
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.
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.
Results' overview:
-Novel control schemes for enhanced sensitivity and polarization transfer, with rate improved by over a factor of 2.
-Demonstration of NV magnetic sensing with compressed sensing, achieving improved bandwidth of over a factor of 4 for similar sensitivity.
-Study of multiple spin baths - characterization of radicals through noise on shallow NVs, demonstrating a sensitivity of ~10 nMol/Hz^½ with sub-micron resolution.
-AZE-related sensitivity enhancements up to ≥500-fold reductions in the effective acquisition times for NMR experiments involving RNA imino protons, like those forming the genome of the SARS-CoV-2 viruses.
-Temperature sensing (with possible application in biological samples) based on ODMR measurement (sensitivity 5 mK/Hz^½) in bulk diamond.
-ODMR sensing protocols with NV centres showing 40 nT/Hz^1/2 magnetic sensitivity in continuous excitation (70 nT/Hz^½ in biocompatible conditions).
-A complex molecular environment (as murine brain) was explored using both in and ex vivo at high (14.1 15.2T) fields, using both conventional 2D NMR and our new AZE technique. In conjunction, these high field experiments have revealed ca. 10 and 29 metabolites in in- and ex-vivo, respectively, and lead to the assignment of 137 cross-peaks in total.
-Neuronal temperature variation (1K) at single-cell level correlated to modified network firing pattern detected via nanodiamond sensor based on ODMR.
-Theoretical and experimental demonstration of NV-spin coherence time enhancement by 10^3 due to nuclear spin bath noise filtering via AZE measurements.
-Enhanced coupling and polarization transfer between NV and the surrounding nuclear spin bath, through tuning the magnetic field through the level anticrossing, leading to longer coherence times (T2*, by up to almost a factor of 2).
-Enhanced ODMR magnetic sensing via both compressed sensing and machine learning schemes - achieve nearly order-of-magnitude improvement in the sensitivity-bandwidth product.
-Advanced implementations of noise sensing to singlet-triplet transitions in retinal excitation dynamics and to noise in magnetic excitations.
-AZE was used to optimize heteronuclear polarization transfer in the presence of fast solvent chemical exchanges, via J-based cross polarization (CP) strategies.
-In the area of biomolecule/pharmaceutical NMR, it was realized that the repolarization effects used so far on the basis of water exchanges, could also be leveraged in the presence of paramagnetic centers and/or when targeting low-abundance species like 13C in organic molecules.
-About x200 enhancement in SNR per sqrt unit time for certain 2D NMR experiments on nucleus acids. About x50 for certain 2D protein experiments. Enabling 17O and 14N MRI based on water detection.
-Characterization of nanodiamond ODMR temperature sensors to be used in Ramos’ cells after internalization with endocytosis, via a home-built scanning confocal microscope with capabilities of delivering microwave (MW) pulses to a diamond sample.
-In ND-based thermometry, by exploiting our ODMR technique in the weak orthogonal regime we improved the coherence time to T_2^*=2 µs, much longer than the standard high field states (T_2^*=0.88 µs). This implies an improvement in the temperature sensitivity of a factor \sqrt{2}.
-ML algorithms allowed us to get a x3 reduction in the number of required measurements for noise spectroscopy experiments via a single NV center in diamond (at room temperature).
-In NV-based magnetic sensing, our ML approach error scales better than the traditional raster scan, with an error of about 1 MHz with just 10 percent of the data points.
-Combining our advanced decoupling sequences with the pulsePol sequence for polarization transfer improves achievable target spin polarization by approx. x10.
-We have demonstrated robust noise characterization in the presence of coherent errors, with significantly improved robustness compared to standard techniques (in this case Ramsey interferometry). In this context, we demonstrated up to x2 better accuracy in the extracted T2*.
Their Exploitation and Dissemination are shown in www.pathos-fetopen.eu.
-Novel control schemes for enhanced sensitivity and polarization transfer, with rate improved by over a factor of 2.
-Demonstration of NV magnetic sensing with compressed sensing, achieving improved bandwidth of over a factor of 4 for similar sensitivity.
-Study of multiple spin baths - characterization of radicals through noise on shallow NVs, demonstrating a sensitivity of ~10 nMol/Hz^½ with sub-micron resolution.
-AZE-related sensitivity enhancements up to ≥500-fold reductions in the effective acquisition times for NMR experiments involving RNA imino protons, like those forming the genome of the SARS-CoV-2 viruses.
-Temperature sensing (with possible application in biological samples) based on ODMR measurement (sensitivity 5 mK/Hz^½) in bulk diamond.
-ODMR sensing protocols with NV centres showing 40 nT/Hz^1/2 magnetic sensitivity in continuous excitation (70 nT/Hz^½ in biocompatible conditions).
-A complex molecular environment (as murine brain) was explored using both in and ex vivo at high (14.1 15.2T) fields, using both conventional 2D NMR and our new AZE technique. In conjunction, these high field experiments have revealed ca. 10 and 29 metabolites in in- and ex-vivo, respectively, and lead to the assignment of 137 cross-peaks in total.
-Neuronal temperature variation (1K) at single-cell level correlated to modified network firing pattern detected via nanodiamond sensor based on ODMR.
-Theoretical and experimental demonstration of NV-spin coherence time enhancement by 10^3 due to nuclear spin bath noise filtering via AZE measurements.
-Enhanced coupling and polarization transfer between NV and the surrounding nuclear spin bath, through tuning the magnetic field through the level anticrossing, leading to longer coherence times (T2*, by up to almost a factor of 2).
-Enhanced ODMR magnetic sensing via both compressed sensing and machine learning schemes - achieve nearly order-of-magnitude improvement in the sensitivity-bandwidth product.
-Advanced implementations of noise sensing to singlet-triplet transitions in retinal excitation dynamics and to noise in magnetic excitations.
-AZE was used to optimize heteronuclear polarization transfer in the presence of fast solvent chemical exchanges, via J-based cross polarization (CP) strategies.
-In the area of biomolecule/pharmaceutical NMR, it was realized that the repolarization effects used so far on the basis of water exchanges, could also be leveraged in the presence of paramagnetic centers and/or when targeting low-abundance species like 13C in organic molecules.
-About x200 enhancement in SNR per sqrt unit time for certain 2D NMR experiments on nucleus acids. About x50 for certain 2D protein experiments. Enabling 17O and 14N MRI based on water detection.
-Characterization of nanodiamond ODMR temperature sensors to be used in Ramos’ cells after internalization with endocytosis, via a home-built scanning confocal microscope with capabilities of delivering microwave (MW) pulses to a diamond sample.
-In ND-based thermometry, by exploiting our ODMR technique in the weak orthogonal regime we improved the coherence time to T_2^*=2 µs, much longer than the standard high field states (T_2^*=0.88 µs). This implies an improvement in the temperature sensitivity of a factor \sqrt{2}.
-ML algorithms allowed us to get a x3 reduction in the number of required measurements for noise spectroscopy experiments via a single NV center in diamond (at room temperature).
-In NV-based magnetic sensing, our ML approach error scales better than the traditional raster scan, with an error of about 1 MHz with just 10 percent of the data points.
-Combining our advanced decoupling sequences with the pulsePol sequence for polarization transfer improves achievable target spin polarization by approx. x10.
-We have demonstrated robust noise characterization in the presence of coherent errors, with significantly improved robustness compared to standard techniques (in this case Ramsey interferometry). In this context, we demonstrated up to x2 better accuracy in the extracted T2*.
Their Exploitation and Dissemination are shown in www.pathos-fetopen.eu.
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.