Periodic Reporting for period 2 - MUQUABIS (Multiscale quantum bio-imaging and spectroscopy)
Berichtszeitraum: 2024-01-01 bis 2025-06-30
The MUQUABIS Project aims at developing quantum-enhanced tools for sensing and imaging of biological processes. The combination of multiscale and multiphysics measurements will offer an unprecedentedly complete picture of the structural and functional behaviour of cardiac preparations – from molecule, to cell and tissue scales. The developed sensors will feature non-invasiveness, sensitivity, and spatio-temporal resolutions which are out-of-reach of their classical counterparts, paving the way to a next generation of quantum-based tools and protocols for medical diagnostics and treatments.
The main goals are the following:
1) Develop quantum technologies for magnetic and optical imaging and spectroscopy, specifically designed for biological applications.
1A) Develop a comprehensive quantum magnetic sensing and imaging platform based on nitrogen-vacancy (NV) centers in diamond, tailored for investigating cardiac layer dynamics.
1B) Explore the potential of quantum frequency combs and quantum-enhanced frequency comb spectro-imaging for biological sensing.
1C) Develop and characterize non-classical infrared light sources for quantum-enhanced imaging and spectroscopy applications.
2) Validate the developed quantum sensors in laboratory experiments on cardiac preparations, to obtain a characterization of features useful to distinguish healthy and diseased samples.
3) Assess the advantage of the developed quantum technologies compared to their classical counterparts, and perform a feasibility study of the industrialization of such technologies.
The main goals are the following:
1) Develop quantum technologies for magnetic and optical imaging and spectroscopy, specifically designed for biological applications.
1A) Develop a comprehensive quantum magnetic sensing and imaging platform based on nitrogen-vacancy (NV) centers in diamond, tailored for investigating cardiac layer dynamics.
1B) Explore the potential of quantum frequency combs and quantum-enhanced frequency comb spectro-imaging for biological sensing.
1C) Develop and characterize non-classical infrared light sources for quantum-enhanced imaging and spectroscopy applications.
2) Validate the developed quantum sensors in laboratory experiments on cardiac preparations, to obtain a characterization of features useful to distinguish healthy and diseased samples.
3) Assess the advantage of the developed quantum technologies compared to their classical counterparts, and perform a feasibility study of the industrialization of such technologies.
The MUQUABIS Consortium developed quantum sensing and imaging techniques and experimental platforms for the investigation of biological samples; in parallel worked to the generation, characterization, and modeling of biological case studies for the investigation of cardiac magnetic activity and arrhythmia dynamics.
1) Biological sample generation, characterization, and modeling. CNR and UNIFI generated hiPSC-derived cardiomyocytes (hiPSC-CMs) from urine cells using lentiviral and CRISPR-Cas9 reprogramming. Electrophysiological analysis showed slower kinetics of action potential and spontaneous beating than adult cells. Optogenetic CheRiff-GFP expression was engineered in HEK293 and hiPSCs, enabling precise light-driven excitation. ICRC differentiated CPVT patient-derived hiPSCs into cardiomyocytes and analyzed them using multielectrode arrays and FluoVolt imaging, revealing isoprenaline-dependent beat modulation. Fibrotic microenvironments were modeled using decellularized matrices from WT and YAP1-deficient fibroblasts, reproducing arrhythmic and fibrotic features. UCBM, supported by CNR and UNIFI, developed phenomenological models of magnetic field generated by action potential propagation in hiPSCs.
2) Quantum magnetometry and magnetic imaging of biosamples. HQT, in collaboration with CNR, JGU, and HUJI, fabricated high-quality, ultra-pure C-12 diamond substrates optimized for NV–based quantum sensing. CNR developed a hybrid NV/optical platform for magnetic and electrical mapping of cardiac tissues, optimized in collaboration with UCBM, UNIFI, and ICRC. HUJI developed a bio-compatible NV sensing system with integrated microwave delivery and 3D-printed chambers for live-cell experiments, to be tested at ICRC. JGU and HUJI jointly advanced radical sensing using NV relaxometry at near-zero magnetic fields. CNR and HUJI collaborated on theoretical and algorithmic frameworks for enhancing NV sensitivity, including noise-resilient control, ML-assisted data acquisition, and quantum image processing, essential for quantum bioimaging integration.
3) Quantum-enhanced dual-comb spectroscopy and hyperspectral imaging. QLIBRI, with contributions from MPG/MPQ and FvB/MBI, improved high-finesse fiber microcavities through precision mirror fabrication and automated tilt correction, achieving stable 60×60 µm² scanning for biological imaging. Proof-of-concept demonstrations by MPQ, and FvB/MBI, and QLIBRI achieved cavity-enhanced dual-comb microscopy, imaging patterned samples across multiple wavelengths within 20 seconds for 40,000-pixel datasets—confirming its biomedical potential. FvB/MBI also advanced GHz photon-pair generation at telecom wavelengths with high signal-to-noise ratios. Collaborative preliminary measurements on thin biological sections validated reproducibility and wavelength-dependent optical responses, preparing for upcoming frequency-comb experiments.
4) Non-classical infrared radiation sources. CNR designed near-IR cavities for quantum sensing, achieving shot-noise-limited operation above 3 MHz using self-homodyne detection. With support of PPQS, CNR improved mid-IR squeezing via feed-forward noise suppression (>40 dB), engineered advanced THz quantum cascade laser (QCL) combs with >1 THz spectral coverage with uniform modes, realized a mid-IR balanced homodyne detector (41% quantum efficiency), and characterized coherent mid-IR sources—identifying interband cascade lasers as optimal for sensitive bio-spectroscopy. LDO, supported by CNR, developed SPDC-based entangled photon sources (810/1550 nm) with up to 3.5% heralding efficiency for quantum imaging, and cooperated with UCBM to establish a quantum imaging setup using undetected photons and selected biological targets for forthcoming imaging trials.
1) Biological sample generation, characterization, and modeling. CNR and UNIFI generated hiPSC-derived cardiomyocytes (hiPSC-CMs) from urine cells using lentiviral and CRISPR-Cas9 reprogramming. Electrophysiological analysis showed slower kinetics of action potential and spontaneous beating than adult cells. Optogenetic CheRiff-GFP expression was engineered in HEK293 and hiPSCs, enabling precise light-driven excitation. ICRC differentiated CPVT patient-derived hiPSCs into cardiomyocytes and analyzed them using multielectrode arrays and FluoVolt imaging, revealing isoprenaline-dependent beat modulation. Fibrotic microenvironments were modeled using decellularized matrices from WT and YAP1-deficient fibroblasts, reproducing arrhythmic and fibrotic features. UCBM, supported by CNR and UNIFI, developed phenomenological models of magnetic field generated by action potential propagation in hiPSCs.
2) Quantum magnetometry and magnetic imaging of biosamples. HQT, in collaboration with CNR, JGU, and HUJI, fabricated high-quality, ultra-pure C-12 diamond substrates optimized for NV–based quantum sensing. CNR developed a hybrid NV/optical platform for magnetic and electrical mapping of cardiac tissues, optimized in collaboration with UCBM, UNIFI, and ICRC. HUJI developed a bio-compatible NV sensing system with integrated microwave delivery and 3D-printed chambers for live-cell experiments, to be tested at ICRC. JGU and HUJI jointly advanced radical sensing using NV relaxometry at near-zero magnetic fields. CNR and HUJI collaborated on theoretical and algorithmic frameworks for enhancing NV sensitivity, including noise-resilient control, ML-assisted data acquisition, and quantum image processing, essential for quantum bioimaging integration.
3) Quantum-enhanced dual-comb spectroscopy and hyperspectral imaging. QLIBRI, with contributions from MPG/MPQ and FvB/MBI, improved high-finesse fiber microcavities through precision mirror fabrication and automated tilt correction, achieving stable 60×60 µm² scanning for biological imaging. Proof-of-concept demonstrations by MPQ, and FvB/MBI, and QLIBRI achieved cavity-enhanced dual-comb microscopy, imaging patterned samples across multiple wavelengths within 20 seconds for 40,000-pixel datasets—confirming its biomedical potential. FvB/MBI also advanced GHz photon-pair generation at telecom wavelengths with high signal-to-noise ratios. Collaborative preliminary measurements on thin biological sections validated reproducibility and wavelength-dependent optical responses, preparing for upcoming frequency-comb experiments.
4) Non-classical infrared radiation sources. CNR designed near-IR cavities for quantum sensing, achieving shot-noise-limited operation above 3 MHz using self-homodyne detection. With support of PPQS, CNR improved mid-IR squeezing via feed-forward noise suppression (>40 dB), engineered advanced THz quantum cascade laser (QCL) combs with >1 THz spectral coverage with uniform modes, realized a mid-IR balanced homodyne detector (41% quantum efficiency), and characterized coherent mid-IR sources—identifying interband cascade lasers as optimal for sensitive bio-spectroscopy. LDO, supported by CNR, developed SPDC-based entangled photon sources (810/1550 nm) with up to 3.5% heralding efficiency for quantum imaging, and cooperated with UCBM to establish a quantum imaging setup using undetected photons and selected biological targets for forthcoming imaging trials.
We obtained results in different technological areas, which constitute the ground for quantum bio-sensing and imaging on cardiac preparations.
- We built two complementary apparata for magnetic sensing and imaging with NV centers, one integrating NV-based magnetic imaging and optical electrophysiology, the other implementing NV magnetometry in a 3D-printed chambers to be coupled with a life-sciences microscope. In parallel, we demonstrated optimal control and machine learning-assisted methods to improve NV-diamond sensing.
- We demonstrated cavity-enhanced dual-comb microscopy with resolution of individual cavity modes and raster-scanned multispectral imaging, and we tested it for the first time on biologically relevant sample suitable for investigation with the fibre-based microcavity.
- We developed and characterized quantum light sources and detection systems spanning from the near-infrared to the THz region, and a setup for quantum imaging with undetected photons, to be employed in bioimaging experiments.
- We developed a theoretical framework for simulating and analyzing the magnetic activity associated with cardiac dynamics, focussing on 1D homogeneous and heterogeneous cables for the study of cardiac alternans, and 2D homogenous domain for the simulation of complex magnetic field patterns.
- We built two complementary apparata for magnetic sensing and imaging with NV centers, one integrating NV-based magnetic imaging and optical electrophysiology, the other implementing NV magnetometry in a 3D-printed chambers to be coupled with a life-sciences microscope. In parallel, we demonstrated optimal control and machine learning-assisted methods to improve NV-diamond sensing.
- We demonstrated cavity-enhanced dual-comb microscopy with resolution of individual cavity modes and raster-scanned multispectral imaging, and we tested it for the first time on biologically relevant sample suitable for investigation with the fibre-based microcavity.
- We developed and characterized quantum light sources and detection systems spanning from the near-infrared to the THz region, and a setup for quantum imaging with undetected photons, to be employed in bioimaging experiments.
- We developed a theoretical framework for simulating and analyzing the magnetic activity associated with cardiac dynamics, focussing on 1D homogeneous and heterogeneous cables for the study of cardiac alternans, and 2D homogenous domain for the simulation of complex magnetic field patterns.