Periodic Reporting for period 1 - MUQUABIS (Multiscale quantum bio-imaging and spectroscopy)
Reporting period: 2022-07-01 to 2023-12-31
The MUQUABIS Project targets at developing quantum-enhanced tools for sensing and imaging of biological processes. These tools are built on the synergy of new concepts for quantum frequency combs, non-classical infrared laser sources, and diamond-based magnetic microscopy, and aim at advance the current understanding of biological mechanisms that lead to cardiac diseases and their spatio-temporal dynamics. 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 of the project are the following:
i) Develop a comprehensive quantum magnetic sensing and imaging platform based on nitrogen-vacancy (NV) centers in diamond, tailored for the investigation of cardiac layer dynamics;
ii) Explore the potential of quantum frequency combs and quantum-enhanced frequency comb spectro-imaging for biological sensing;
iii) Develop and characterize non-classical infrared light sources for quantum-enhanced imaging and spectroscopy applications;
iv) Validate the developed quantum sensors in laboratory experiments on cardiac preparations, to obtain a characterization of features useful to distinguish healthy and diseased samples;
v) Assess the advantage of the quantum technologies developed in the Project compared to their classical counterparts, and perform a feasibility study of the industrialization of such technologies.
The main goals of the project are the following:
i) Develop a comprehensive quantum magnetic sensing and imaging platform based on nitrogen-vacancy (NV) centers in diamond, tailored for the investigation of cardiac layer dynamics;
ii) Explore the potential of quantum frequency combs and quantum-enhanced frequency comb spectro-imaging for biological sensing;
iii) Develop and characterize non-classical infrared light sources for quantum-enhanced imaging and spectroscopy applications;
iv) Validate the developed quantum sensors in laboratory experiments on cardiac preparations, to obtain a characterization of features useful to distinguish healthy and diseased samples;
v) Assess the advantage of the quantum technologies developed in the Project compared to their classical counterparts, and perform a feasibility study of the industrialization of such technologies.
In the first reporting period, we developed the technological building blocks for magnetic quantum imaging and non-classical light spectro-imaging, to be applied later in the Project to the investigation of cardiac cell and tissues dynamics.
The main achievements are:
WP1 – NV magnetometry
• We demonstrated novel sensing schemes based on compressed sensing and machine learning to improve the sensitivity in optically detected magnetic resonance with NV sensors.
• We established a novel diamond surface termination technique based on nitrogen plasma under non-damaging conditions, achieving significant improvement in NV optical stability and quantum coherence.
• In close interaction with WP4, we designed a new apparatus combining bio-optimized wide-field NV-based quantum magnetic imaging and optical electrophysiology.
WP2 - Quantum Dual-Combs
• We developed high-flux frequency-comb sources of photons pairs based on parametric down-conversion of a mode-locked laser of high repetition frequency. We developed a setup to characterize these sources and to verify the linear scaling of two-photon excitations.
• Using carefully designed setups involving low light levels, we demonstrated that the quantum noise limit can be reproducibly approached, not only in the ultraviolet but also in the mid-infrared spectral region.
• We designed a high-finesse fiber cavity optimized for the coupling to a frequency comb. In view of integration into a device, we setup and installed a complete scanning cavity system.
WP3 - Non-classical infrared radiation sources
• We demonstrated the generation of quantum correlated twin beams through a cascaded process of optical parametric oscillation in a doubly-resonant second-harmonic-generation system.
• We designed and assembled a mid-IR optical parametric oscillator (OPO), with emission wavelength of 3.8 µm; we characterized the intensity/frequency noise features of different types of lasers seeding the Tm:fiber amplifier pumping the OPO.
• We developed broadband harmonic frequency combs of a pre-defined order in Quantum Cascade Lasers (QCLs) with emission in the THz spectral region, by design with two distinctive architectures: by patterning regularly-spaced defects on the top surface of a double-metal Fabry-Perot QCL; and by implementing multilayer graphene scatters on the top contact of THz QCLs.
• We characterized several mid-infrared coherent sources via balanced homodyne detection, finding superior performance of Interband Cascade Lasers (ICLs) in terms of intensity noise spectra.
WP4 - Quantum imaging, spectroscopy and modeling of cardiac cell dynamics
• We developed a protocol for preparation of beating monolayers of contracting cardiomyocytes from cell lines (healthy control), and a method for measuring the contractile activity of the monolayer by detection of calcium transients using a calcium sensitive dye Fluo-4 AM.
• We developed numerical simulations of the magnetic signal produced by cardiac cell monolayers to support the design of the quantum magnetic imager of WP1. We studied the magnetic field generated by collective cellular behaviors in terms of spatiotemporal excitation waves.
The main achievements are:
WP1 – NV magnetometry
• We demonstrated novel sensing schemes based on compressed sensing and machine learning to improve the sensitivity in optically detected magnetic resonance with NV sensors.
• We established a novel diamond surface termination technique based on nitrogen plasma under non-damaging conditions, achieving significant improvement in NV optical stability and quantum coherence.
• In close interaction with WP4, we designed a new apparatus combining bio-optimized wide-field NV-based quantum magnetic imaging and optical electrophysiology.
WP2 - Quantum Dual-Combs
• We developed high-flux frequency-comb sources of photons pairs based on parametric down-conversion of a mode-locked laser of high repetition frequency. We developed a setup to characterize these sources and to verify the linear scaling of two-photon excitations.
• Using carefully designed setups involving low light levels, we demonstrated that the quantum noise limit can be reproducibly approached, not only in the ultraviolet but also in the mid-infrared spectral region.
• We designed a high-finesse fiber cavity optimized for the coupling to a frequency comb. In view of integration into a device, we setup and installed a complete scanning cavity system.
WP3 - Non-classical infrared radiation sources
• We demonstrated the generation of quantum correlated twin beams through a cascaded process of optical parametric oscillation in a doubly-resonant second-harmonic-generation system.
• We designed and assembled a mid-IR optical parametric oscillator (OPO), with emission wavelength of 3.8 µm; we characterized the intensity/frequency noise features of different types of lasers seeding the Tm:fiber amplifier pumping the OPO.
• We developed broadband harmonic frequency combs of a pre-defined order in Quantum Cascade Lasers (QCLs) with emission in the THz spectral region, by design with two distinctive architectures: by patterning regularly-spaced defects on the top surface of a double-metal Fabry-Perot QCL; and by implementing multilayer graphene scatters on the top contact of THz QCLs.
• We characterized several mid-infrared coherent sources via balanced homodyne detection, finding superior performance of Interband Cascade Lasers (ICLs) in terms of intensity noise spectra.
WP4 - Quantum imaging, spectroscopy and modeling of cardiac cell dynamics
• We developed a protocol for preparation of beating monolayers of contracting cardiomyocytes from cell lines (healthy control), and a method for measuring the contractile activity of the monolayer by detection of calcium transients using a calcium sensitive dye Fluo-4 AM.
• We developed numerical simulations of the magnetic signal produced by cardiac cell monolayers to support the design of the quantum magnetic imager of WP1. We studied the magnetic field generated by collective cellular behaviors in terms of spatiotemporal excitation waves.
We obtained results in the following technological areas, which constitute the ground for quantum bio-sensing and imaging on cardiac preparations.
- We developed sensing and data processing schemes demonstrated on diamond color centers that will allow to enhance accuracy of high-bandwidth magnetometry and magnetic noise spectroscopy of bio-samples.
- We demonstrated, for the first time, quantum-noise-limited dual comb emission in the mid-infrared, which we will employ in cell membrane spectroscopy.
- We developed near-infrared quantum-correlated twin beams, and characterized new mid-infrared sources in terms of intensity noise spectra, both very promising for application in spectroscopy and spectro-imaging of biological samples. For extending the operability to the THz spectral region, we implemented broadband harmonic frequency comb generation of a pre-defined order in QCLs based on graphene-layers technology.
- We showed reproducible cell cultures of contractile cardiomyocytes from pluripotent stem cells and measured their response to the pharmacological stimulus. We developed new semi-automated analysis of calcium transients which can facilitate high throughput screening of cardioactive drugs. We plan to make the method available in the form of a web-app to increase the uptake by wider community.
- We proposed a first-of-its-kind theoretical framework comprising cardiac cell electrophysiology and associated electro-magnetic field generation, focusing on the patterns occurring during cardiac arrhythmias. Such a tool would be a valuable support for the prediction and analysis of cardiac diseases within groundbreaking quantum based diagnostic medical technologies.
- We developed sensing and data processing schemes demonstrated on diamond color centers that will allow to enhance accuracy of high-bandwidth magnetometry and magnetic noise spectroscopy of bio-samples.
- We demonstrated, for the first time, quantum-noise-limited dual comb emission in the mid-infrared, which we will employ in cell membrane spectroscopy.
- We developed near-infrared quantum-correlated twin beams, and characterized new mid-infrared sources in terms of intensity noise spectra, both very promising for application in spectroscopy and spectro-imaging of biological samples. For extending the operability to the THz spectral region, we implemented broadband harmonic frequency comb generation of a pre-defined order in QCLs based on graphene-layers technology.
- We showed reproducible cell cultures of contractile cardiomyocytes from pluripotent stem cells and measured their response to the pharmacological stimulus. We developed new semi-automated analysis of calcium transients which can facilitate high throughput screening of cardioactive drugs. We plan to make the method available in the form of a web-app to increase the uptake by wider community.
- We proposed a first-of-its-kind theoretical framework comprising cardiac cell electrophysiology and associated electro-magnetic field generation, focusing on the patterns occurring during cardiac arrhythmias. Such a tool would be a valuable support for the prediction and analysis of cardiac diseases within groundbreaking quantum based diagnostic medical technologies.