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Multiphoton Microscopy and Ultrafast Spectroscopy: Imaging meets Quantum

Periodic Reporting for period 1 - MUSIQ (Multiphoton Microscopy and Ultrafast Spectroscopy: Imaging meets Quantum)

Période du rapport: 2019-04-01 au 2021-03-31

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 is designed as an innovative research and training network recruiting 15 Early Stage Researchers (ESRs) to work toward the central ambitious goal of developing the next-generation optical microscopy exploiting quantum coherent nonlinear phenomena. The network brings together 7 world-leading academics 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 established an intersectoral training and research programme at the physics/chemistry/life science interface aimed at creating the next generation of skilled well-connected scientists that will pioneer the ‘quantum microscopes of tomorrow’.
The scientific and training objectives of MUSIQ are:
O1: Investigate nonlinear optical phenomena originating from the intrinsic response of natural biomolecules, to achieve label-free imaging and overcome artefacts from sample staining/fluorescence methods.
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 metallic (plasmonic) nanostructures.
T1: To 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: To 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 provided by 7 world-leading academic institutions, 5 high-tech companies and 3 professional partners in social sciences and dissemination, across 9 European countries.
MUSIQ has successfully recruited 15 ESRs enrolled in PhD programmes at leading Universities across Europe.
Toward MUSIQ’s first scientific objective, significant progress has been made with coherent Raman scattering (CRS) microscopy modalities, which offer chemical specificity while being label-free. Innovative microscope designs have been developed and 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, progress has been made toward developing new bio-compatible Raman probes and quantitative image analysis methodologies.
Toward MUSIQ’s second scientific objective, beneficiaries have been working on instrumentation technology developments beyond state of the art and on the application of existing experimental and computational techniques. Highlights include i) the development of an innovative type of ultrafast 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, iii) the study of ultrafast coherent dynamics in natural and bio-mimetic supramolecular complexes, and iv) unravelling quantum coherent coupling effects in single quantum dots and quantum dot molecules.
The third objective seeks to increase the spatial resolution and detection sensitivity of coherent nonlinear microscopy by exploiting plasmonic nanostructures. Main results include i) the design and fabrication of novel plasmonic nano-antennas, ii) the demonstration of strong coherent coupling between a single molecule and a plasmonic cavity at room temperature, iii) the demonstration of CRS from organic polymer molecules local field enhanced at the nanoscale by a single gold nanorods, iv) the development and quantitative characterisation of individual gold nanoparticle-protein conjugates for controlled cellular uptake.
As to the training objectives, in addition to individual research projects each ESR has secondment opportunities with academic and non-academic partners, to facilitate knowledge exchange. The training programme also includes 6 weeks of network-wide events to equip the ESRs with the combination of research-related and transferable competences needed to succeed in the European science, technology and innovation sector. To date, 3 MUSIQ weeks have occurred comprising 3 scientific Schools, 2 scientific Symposia, 2 training courses in transferable skills and a training course in image analysis software.
Notably, a key feature of MUSIQ’s communication plan was to create a series of Innovation Newsletters, written by the ESRs and published every 6 months on the website, with a focus on the latest innovation related to multiphoton microscopy and bioimaging. Two Innovation Newsletters have been published in October 2020 and March 2021. In addition, MUSIQ has produced a technology Roadmap about the challenges and future directions of optical microscopy exploiting quantum coherent nonlinear phenomena. Such Roadmap, co-authored by all ESRs and PIs, has been accepted in May 2021 for publication in the Journal of Optics.
MUSIQ will push forward the development of the next-generation optical microscopy exploiting quantum coherent nonlinear phenomena. Realising such pioneering technology will have an impact at many levels:
Science: by unravelling quantum coherences in biomolecules in a way that has not been possible before. This will pave 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 its application to the biomedical and pharmaceutical industrial sectors.
Society: through the improvement in our health and quality of life by the much better understanding and diagnosis of diseases, and the development of new drugs to cure/prevent illnesses, enabled by this technology.
Innovation Capacity: MUSIQ will train 15 ESRs on a unique mix of highly advanced experimental and computational skills, thus contributing to improving European innovation capacity.
Overview of MUSIQ work packages elucidating its research and training ambition.