Periodic Reporting for period 2 - MUSIQ (Multiphoton Microscopy and Ultrafast Spectroscopy: Imaging meets Quantum)
Reporting period: 2021-04-01 to 2023-09-30
In the quest to decipher the chain of life, from molecules to cells, the biophysical questions being asked increasingly demand techniques that can identify specific biomolecules in their native environment, at the smallest possible scale, and can measure biomolecular interactions quantitatively without perturbing the system under observation. Laser-based optical microscopy is a key technology to drive this progress. However, many challenges remain around issues such as label-free biomolecular specificity and single molecule sensitivity.
New opportunities toward achieving biomolecular specificity at very high temporal resolution have been brought by the development of techniques which address the importance of quantum coherences, with the potential to unravel the fundamental machinery of Nature. Yet, measuring quantum phenomena with an optical microscope is technically challenging, and far from real-world biological applications.
MUSIQ has been designed as an innovative network and recruited 15 Early Stage Researchers (ESRs) to work towards the central ambitious goal of developing the next-generation optical microscopy exploiting quantum coherent nonlinear phenomena. The network has brought together 7 world-leading academic institutions and 5 high tech companies at the forefront of optical microscopy and ultrafast laser technology developments merged with fundamental understanding of coherent light-matter interaction phenomena, development of quantitative image analysis tools, and biomedical/pharmaceutical real-world applications.
MUSIQ has delivered 3 scientific and 2 training objectives:
O1: Investigate nonlinear optical phenomena originating from the intrinsic response of natural biomolecules, to achieve label-free imaging.
O2: Combine nonlinear imaging with ultrafast spectroscopy to increase specificity and unravel quantum coherences in biomolecules.
O3: Achieve single molecule detection and super-resolution in coherent nonlinear imaging via the enhancement of the light field in the vicinity of plasmonic nanostructures.
T1: Form the next generation of innovative, highly skilled, well-connected scientists by implementing a multidisciplinary intersectoral training and research programme at the physics/chemistry/life sciences interface and creating a modern professional profile which is currently highly in demand by both academia and high-tech industries.
T2: Enhance the career perspective of the ESRs by training them in a broad range of cutting-edge scientific, technical and transferable skills, through a unique combination of projects, secondments, and tailored courses.
New opportunities toward achieving biomolecular specificity at very high temporal resolution have been brought by the development of techniques which address the importance of quantum coherences, with the potential to unravel the fundamental machinery of Nature. Yet, measuring quantum phenomena with an optical microscope is technically challenging, and far from real-world biological applications.
MUSIQ has been designed as an innovative network and recruited 15 Early Stage Researchers (ESRs) to work towards the central ambitious goal of developing the next-generation optical microscopy exploiting quantum coherent nonlinear phenomena. The network has brought together 7 world-leading academic institutions and 5 high tech companies at the forefront of optical microscopy and ultrafast laser technology developments merged with fundamental understanding of coherent light-matter interaction phenomena, development of quantitative image analysis tools, and biomedical/pharmaceutical real-world applications.
MUSIQ has delivered 3 scientific and 2 training objectives:
O1: Investigate nonlinear optical phenomena originating from the intrinsic response of natural biomolecules, to achieve label-free imaging.
O2: Combine nonlinear imaging with ultrafast spectroscopy to increase specificity and unravel quantum coherences in biomolecules.
O3: Achieve single molecule detection and super-resolution in coherent nonlinear imaging via the enhancement of the light field in the vicinity of plasmonic nanostructures.
T1: Form the next generation of innovative, highly skilled, well-connected scientists by implementing a multidisciplinary intersectoral training and research programme at the physics/chemistry/life sciences interface and creating a modern professional profile which is currently highly in demand by both academia and high-tech industries.
T2: Enhance the career perspective of the ESRs by training them in a broad range of cutting-edge scientific, technical and transferable skills, through a unique combination of projects, secondments, and tailored courses.
MUSIQ has trained 15 ESRs enrolled in PhD programmes at leading Universities.
Regarding MUSIQ’s first scientific objective, significant work has been devoted to developing coherent Raman scattering (CRS) microscopy modalities, which offer chemical specificity while being label-free. Innovative microscope designs have been demonstrated, featuring improved performances in terms of controlling the excitation and detection of light, and in turn increasing the image contrast, sensitivity and specificity compared to existing systems. Furthermore, new bio-compatible Raman probes and quantitative image analysis methodologies have been developed. As a conclusion of the project, highlights of this objective include the demonstration of wide-field CRS microscopy enabled by advances in high-power ultrafast laser sources, the development and exploitation of vibrational Raman tags, and the biomedical application of CRS microscopy for diseased tissue diagnosis and drug delivery.
Toward MUSIQ’s second scientific objective, beneficiaries have been working on instrumentation technology developments and the application of computational techniques. As a conclusion of the project, highlights include i) the development of an innovative ultrafast transient holographic microscope, combining high temporal (<100 fs) and spatial (<500 nm) resolution, ii) the development of a novel set-up to perform ultrafast mid-IR/vibrational micro-spectroscopy of organic molecules, and iii) the measurement of ultrafast quantum coherences in bio/organic molecules, such as porphyrins and fluorescent proteins, in agreement with quantum mechanical simulations.
The third MUSIQ’s objective focused on increasing the spatial resolution and detection sensitivity of coherent nonlinear microscopy by exploiting plasmonic nanostructures. As a conclusion of the project, main results include i) the design and fabrication of novel plasmonic nano-antennas, ii) the demonstration of local-field enhanced CRS near a single nano-antenna for label-free chemical sensing at the nanoscale, iii) the strong coupling between single molecules and nano-cavities at room temperature, and iv) the development and quantitative characterisation of individual gold nanoparticle-protein conjugates for controlled cellular uptake and therapeutic delivery.
As to the training objectives, in addition to individual research projects, each ESR benefited from secondment opportunities with academic and non-academic partners. Moreover, the training programme included 6 weeks of network-wide events. Within these 6 MUSIQ weeks, 4 scientific Schools, 4 scientific Symposia, and 7 training courses in transferable skills were delivered.
Notably, a key feature of MUSIQ’s communication plan has been to create a series of 5 Innovation Newsletters, written by the ESRs and published on the website, with a focus on the latest innovation related to multiphoton microscopy and bioimaging. In addition, MUSIQ has produced two technology Roadmaps on the challenges and future directions of optical microscopy exploiting quantum coherent nonlinear phenomena. The 1st Roadmap, co-authored by all ESRs and PIs, was published open access in the Journal of Optics in 2021. Other important elements of MUSIQ’s dissemination activities have been i) a series of “science slam” short videos produced by the ESRs and posted on social media, as an outreach resource for the wider public, ii) over 20 papers published/submitted by the ESRs to scientific international peer reviewed journals, and iii) over 40 presentations of the ESRs at national/international conferences.
Regarding MUSIQ’s first scientific objective, significant work has been devoted to developing coherent Raman scattering (CRS) microscopy modalities, which offer chemical specificity while being label-free. Innovative microscope designs have been demonstrated, featuring improved performances in terms of controlling the excitation and detection of light, and in turn increasing the image contrast, sensitivity and specificity compared to existing systems. Furthermore, new bio-compatible Raman probes and quantitative image analysis methodologies have been developed. As a conclusion of the project, highlights of this objective include the demonstration of wide-field CRS microscopy enabled by advances in high-power ultrafast laser sources, the development and exploitation of vibrational Raman tags, and the biomedical application of CRS microscopy for diseased tissue diagnosis and drug delivery.
Toward MUSIQ’s second scientific objective, beneficiaries have been working on instrumentation technology developments and the application of computational techniques. As a conclusion of the project, highlights include i) the development of an innovative ultrafast transient holographic microscope, combining high temporal (<100 fs) and spatial (<500 nm) resolution, ii) the development of a novel set-up to perform ultrafast mid-IR/vibrational micro-spectroscopy of organic molecules, and iii) the measurement of ultrafast quantum coherences in bio/organic molecules, such as porphyrins and fluorescent proteins, in agreement with quantum mechanical simulations.
The third MUSIQ’s objective focused on increasing the spatial resolution and detection sensitivity of coherent nonlinear microscopy by exploiting plasmonic nanostructures. As a conclusion of the project, main results include i) the design and fabrication of novel plasmonic nano-antennas, ii) the demonstration of local-field enhanced CRS near a single nano-antenna for label-free chemical sensing at the nanoscale, iii) the strong coupling between single molecules and nano-cavities at room temperature, and iv) the development and quantitative characterisation of individual gold nanoparticle-protein conjugates for controlled cellular uptake and therapeutic delivery.
As to the training objectives, in addition to individual research projects, each ESR benefited from secondment opportunities with academic and non-academic partners. Moreover, the training programme included 6 weeks of network-wide events. Within these 6 MUSIQ weeks, 4 scientific Schools, 4 scientific Symposia, and 7 training courses in transferable skills were delivered.
Notably, a key feature of MUSIQ’s communication plan has been to create a series of 5 Innovation Newsletters, written by the ESRs and published on the website, with a focus on the latest innovation related to multiphoton microscopy and bioimaging. In addition, MUSIQ has produced two technology Roadmaps on the challenges and future directions of optical microscopy exploiting quantum coherent nonlinear phenomena. The 1st Roadmap, co-authored by all ESRs and PIs, was published open access in the Journal of Optics in 2021. Other important elements of MUSIQ’s dissemination activities have been i) a series of “science slam” short videos produced by the ESRs and posted on social media, as an outreach resource for the wider public, ii) over 20 papers published/submitted by the ESRs to scientific international peer reviewed journals, and iii) over 40 presentations of the ESRs at national/international conferences.
MUSIQ has pushed forward the development of the next-generation optical microscopy exploiting quantum coherent nonlinear phenomena. Progressing such pioneering technology delivers impact at many levels:
Science: by unravelling quantum coherences and light matter-interaction phenomena in biomolecules beyond state of the art. This is paving the way to fascinating new discoveries into the fundamental machinery of Nature.
Economy: through the creation of novel multiphoton microscopy instrumentation, with associated new software and data analysis pipelines, and their application to the biomedical and pharmaceutical industrial sectors.
Society: through the improvement in our health and quality of life by the better understanding and diagnosis of diseases, and the development of new drugs to cure/prevent illnesses, enabled by this technology.
Innovation Capacity: MUSIQ has trained 15 ESRs on a unique mix of highly advanced experimental and computational skills, thus contributing to improving European innovation capacity. MUSIQ’s ESRs have excellent career perspectives owing to the high demand for experts in innovative technologies and multidisciplinary research fields.
Science: by unravelling quantum coherences and light matter-interaction phenomena in biomolecules beyond state of the art. This is paving the way to fascinating new discoveries into the fundamental machinery of Nature.
Economy: through the creation of novel multiphoton microscopy instrumentation, with associated new software and data analysis pipelines, and their application to the biomedical and pharmaceutical industrial sectors.
Society: through the improvement in our health and quality of life by the better understanding and diagnosis of diseases, and the development of new drugs to cure/prevent illnesses, enabled by this technology.
Innovation Capacity: MUSIQ has trained 15 ESRs on a unique mix of highly advanced experimental and computational skills, thus contributing to improving European innovation capacity. MUSIQ’s ESRs have excellent career perspectives owing to the high demand for experts in innovative technologies and multidisciplinary research fields.