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Label-free quantitative nanoscopy for molecular specific identification at depth in pristine living biological tissues

Descripción del proyecto

Imagenología nanoscópica «in vivo» sin etiquetas

Los últimos avances en la imagenología óptica hacen posible un nivel de resolución nanoscópica que permite identificar moléculas individuales en las muestras biológicas. Hasta ahora, la nanoscopia de alta resolución se llevaba a cabo marcando las biomoléculas con sondas fluorescentes que alteraban las propiedades de estas, lo que en ocasiones hacía que no resultasen adecuadas para aplicaciones médicas. El proyecto financiado con fondos europeos SPECIPHIC introduce un enfoque totalmente novedoso de la imagenología nanoscópica al utilizar el índice de refracción óptica como sensor molecular. El proyecto se basa en la observación de que la información sobre la polarización, la intensidad y la fase se pueden recuperar de forma cuantitativa con una sensibilidad sin precedentes y con una resolución de imagen equivalente a la de la imagenología normal con sondas fluorescentes. La aplicación de esta tecnología permitirá realizar análisis nanoscópicos dentro de muestras biológicas vivas e intactas.

Objetivo

Optical microscopy has undergone a revolution that now allows us to access molecular resolution (“nanoscopy”) with the identification of specific biomolecules within biological samples. Nanoscopy has become a key approach to decipher the function of living matter since biomolecules are the elementary building blocks. While being a major tool, high-resolution and specificity can only be achieved by tagging the molecules of interest with fluorescent probes, which inevitably alters the samples, making them improper for medical applications including regenerative medicine. The leading dogmas being that (i) nanoscopy cannot be achieved without labelling and (ii) no specific signature from molecules can be retrieved without energy exchange with the sample (e.g. absorption by probes, molecular vibrational interaction).
I propose a complete change of paradigm by introducing label-free nanoscopic imaging using the optical refractive index as a molecular sensor. My ground-breaking approach will be based on our pioneering work which demonstrates that phase, intensity and polarisation information can be quantitatively retrieved with unprecedented sensitivity and with an imaging resolution equivalent to regular imaging with fluorescent probes. I will re-forge this into a single-shot imaging technique capable of beating the optical resolution limit to access nanoscale resolutions, even deep inside living unmodified biological samples. Specific molecular information will be untangled through machine learning algorithms. SPECIPHIC will give birth to the first label-free molecular specific imaging with nanoscale resolution in pristine living biological tissues.
The applicability of my concept will be demonstrated in this ERC starting project with applications in regenerative medicine and oncology, impacting thus directly important societal questions. My new approach will impact many other fields, in the biomedical world first but also in physics and for nanomaterial engineering.

Régimen de financiación

ERC-STG - Starting Grant

Institución de acogida

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Aportación neta de la UEn
€ 1 499 016,00
Dirección
RUE MICHEL ANGE 3
75794 Paris
Francia

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Región
Ile-de-France Ile-de-France Paris
Tipo de actividad
Research Organisations
Enlaces
Coste total
€ 1 499 016,00

Beneficiarios (1)