Descrizione del progetto
Imaging nanoscopico in vivo senza marcature
I recenti progressi nell’imaging ottico consentono un livello di risoluzione nanoscopico con la possibilità di identificare singole molecole nei campioni biologici. Fino ad oggi, è stato possibile ottenere un’alta risoluzione nanoscopica marcando le biomolecole con sonde fluorescenti che ne alterano le proprietà e le rendono a volte non adatte ad applicazioni mediche. Il progetto SPECIPHIC, finanziato dall’UE, introduce un approccio totalmente nuovo per l’imaging nanoscopico senza marcature che utilizza l’indice di rifrazione ottica come sensore molecolare. Il progetto si basa sull’osservazione che le informazioni di fase, intensità e polarizzazione possono essere recuperate quantitativamente con una sensibilità senza precedenti e con una risoluzione di imaging equivalente a quella di un normale imaging con sonde fluorescenti. L’implementazione di questa tecnologia permetterà di accedere ad analisi nanoscopiche all’interno di campioni biologici vivi intatti.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomolecules
- social sciencespolitical sciencespolitical transitionsrevolutions
- natural sciencesphysical sciencesopticsmicroscopy
- medical and health sciencesclinical medicineoncology
- natural sciencescomputer and information sciencesartificial intelligencemachine learning
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
75794 Paris
Francia