Hyperpolarized Surface-enhanced Liquid-State Spectroscopy

Objective

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.