Quantum systems enable some of the most accurate measurements known to man. For example, modern atomic clocks measure time with an accuracy exceeding one second over the age of the universe. Recently, a new class of room temperature, solid state, quantum systems emerged that utilize similar quantum measurement concepts, but measure magnetic fields rather than time. In principle, these quantum sensors based on crystallographic defects in diamond could enable the detection of tiny magnetic fields created by nuclear spins in an individual molecule. Such a measurement could provide important insights into complex molecular biological processes at the level of individual molecules with atomic resolution. Although powerful, current quantum technologies lack the sensitivity and biophysical tools to probe biological systems in a single-molecule regime. To overcome these limitations, this project relies on a novel, interdisciplinary approach that combines research in physics, computer science, materials science, and biophysics. The ability to probe biological systems in such a new regime would be of far reaching consequences to fundamental biological research. At the same time the concepts developed in this project will pave the way to a new generation of biomedical devices based on quantum sensing that could significantly simplify sample preparation and enable high throughput screening at a fraction of today's cost. In parallel, this research project will also contribute to training a new workforce in quantum engineering through the development of new course materials, the establishment of conferences that access the interdisciplinary aspects of quantum sensing, and the creation of workshops that enable scientists from all over the world to get hands-on training in the quantum technologies.

This collaborative, interdisciplinary effort develops quantum sensing capabilities for nuclear magnetic resonance (NMR) spectroscopy of small ensembles and individual biomolecules. Sensing based on nitrogen vacancy (NV) centers in diamond enabled the detection of nuclear spins in single proteins and basic NMR spectra. However, these experiments are unable to provide biological information, require days of data acquisition, and are limited to denatured proteins. Applications to intact proteins remain an open challenge due to limitations in quantum sensing methodology, a lack of single-molecule techniques, and imperfections in diamond material engineering. This project investigates fundamental mechanisms and the engineering of systems that overcome these limitations. Specific objectives include: (1) Theoretical exploration of the fundamental limits in single-molecule NMR, (2) Investigation of quantum metrological protocols for single-molecule NMR, (3) Spectroscopic study of diamond surfaces and their functionalization, and (4) Engineering of a single-molecule platform for quantum sensing devices. Goal 1 employs theoretical methods to investigate the limits of single-molecule NMR in the context of multi-parameter sensing under decoherence. Goal 2 develops and benchmarks single-molecule NMR protocols by combining classical signal processing and experimental quantum control. Goal 3 relies on materials science techniques and quantum sensing to understand the origin of decoherence in shallow NV centers. Goal 4 combines methods from single-molecule biophysics and diamond-based NMR spectroscopy for the development of a bio quantum sensor interface. The project will advance understanding of quantum sensing at the intersection of quantum information, engineering, and biology. This will lead to the development and characterization of new computational protocols and devices for single-molecule NMR sensing.

This project is jointly funded by Quantum Leap Big Idea Program, the Division of Chemistry in the Mathematical and Physical Sciences Directorate, and the Office of International Science and Engineering.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

National Science Foundation (NSF)
Directorate for Mathematical and Physical Sciences (MPS)
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Evelyn Goldfield
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University of Chicago
United States
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