Hyperpolarized Surface-enhanced Liquid-State Spectroscopy

Descripción del proyecto

Mejora de la sensibilidad de las señales de resonancia magnética nuclear

La resonancia magnética nuclear (RMN) es una técnica que revela la estructura detallada de las moléculas en química y biología. Sin embargo, su baja sensibilidad limita el estudio de biomoléculas complejas y de interacciones moleculares sutiles. La polarización nuclear dinámica por disolución (dDNP, por sus siglas en inglés) multiplica por diez mil las señales de RMN. Sin embargo, solo funciona para un pequeño grupo de muestras. El objetivo del proyecto HypSurf, financiado por el Consejo Europeo de Investigación, es ampliar el potencial de la dDNP mediante el desarrollo de dispositivos adaptables para equipar sistemas convencionales de RMN con capacidades de dDNP. Los investigadores también desarrollarán un método asistido por inteligencia artificial para ampliar muestras compatibles y demostrarán aplicaciones en biología estructural, biomateriales y química. Se prevé que esta iniciativa establezca un nuevo punto de referencia para el análisis molecular de alta resolución.

Objetivo

Across science, medicine, and industry, nuclear magnetic resonance (NMR) is a key technique with the unique capacity to provide atomistically detailed molecular models. Its primary drawback, however, lies in its low sensitivity, limiting its ability to address critical scientific questions. A potential answer is hyperpolarization via dissolution dynamic nuclear polarization (dDNP), which can amplify NMR sensitivity 10,000-fold.
Despite this promise, dDNP remains a niche method constrained to a narrow range of substrates. Most experiments and nearly all biomolecules remain beyond dDNP’s reach; thus, a plethora of opportunities are missed.
HypSurf aims to exploit the full potential of dDNP by rendering it applicable to all solution-state biomolecular systems – for experiments across the entire biomolecular NMR toolbox. This transformative goal comprises three primary objectives:
1) Universal compatibility will be achieved by building Autonomous Interface Devices (AID): versatile and adaptable instrumentation to seamlessly update any NMR spectrometer with dDNP capabilities.
2) Maximized Substrate Scope will be achieved with artificial intelligence-driven Liquid-state Surface-ENhanced Spectroscopy (LiSENS): a resolution-enhanced method for dDNP-powered studies that uses simply water as a transporter of signal intensity. Thus, the requirement for the 10,000-fold signal boost by dDNP is narrowed down to mere solubility.
3) Confirmation of the versatility and prowess of AID and LiSENS will be achieved by providing super-resolution data at maximized sensitivity for an extensive set of cutting-edge applications in biomimetic materials, structural biology, and chemistry.
HypSurf has the potential to set a new standard for NMR by boosting both resolution and sensitivity by orders of magnitude beyond the current state-of-the-art. With extensive expertise in dDNP instrumentation, NMR methods, and biochemistry, the PI is uniquely positioned to lead this ambitious initiative.