Miniaturization And hyperpolarized Xenon NMR for Ultrahigh Sensitivity – MAX4US

This ambitious project aims at proposing the combined use of hyperpolarized 129Xe NMR and micro-coils as an ultra sensitive biosensing tool for diagnosis purposes. Firstly two main properties of the noble gas will be used: i) the huge gain in sensitivity afforded by the hyperpolarization, ii) the extraordinary receptiveness of xenon to its local environment in terms of NMR parameters and particularly chemical shift. Secondly the detection threshold of the approach will be further significantly lowered through conception of a stopped-flow setup associated with rf micro-coils. This will extend the detection level beyond the femtomole, i. e. several orders of magnitude better than what is achieved by other magnetic resonance techniques.
This project focuses on in vitro studies. In a first application, xenon will be used alone with biological cell suspensions, as a freely diffusive probe of the cell properties. The specific spectral signature of xenon in the inner compartment of living cells will give access to precious structural and morphological information such as plasma membrane permeability, an important property for cancer cell studies. In a second application, dedicated xenon host molecules will be functionalized in order to enable detection of specific biological events. Encapsulation of xenon in such host systems will deeply modify its resonance frequency and therefore further improve the detection capability.
This three-year project groups three laboratories at the forefront of their respective research domain. The physical chemists of the first team will be responsible of the NMR and MRI experiments with hyperpolarized xenon, in which they have recognized experience. This lab has recently acquired a cell culture room and the expertise for that through the recruitment of a biophysicist. Conception of the miniaturized NMR system will be undertaken by the second team which develops innovative processes of chemical writing on polymer substrates (GraftFast™ process), and therefore can build detection coils on flexible substrates by low cost techniques without clean room facilities. The third team is comprised of organic chemists, specialists of the cryptophanes which are ideal hosts for hyperpolarized xenon in molecular imaging applications.
The final objective of this project is to integrate all developments and discoveries in an NMR lab-on-chip type system of general applicability for various in vitro biological diagnoses on commercial NMR spectrometers and imagers.