Single-cell nuclear magnetic resonance spectroscopy with diamond quantum sensors

2026-07-22

Single-cell events are often responsible for biological phenomena, such as drug resistance, cell development or tumorigenesis. Studies on cellular populations mask such characteristics and make single-cell technologies essential for understanding cell biology. However, one of the major analytical tools with the advantage of high molecular specificity and non-invasiveness, nuclear magnetic resonance (NMR) spectroscopy, has been limited in its application to single-cell studies due to its intrinsic low sensitivity. Here, I aim to overcome this limitation by a unique combination of (i) highly sensitive quantum sensors for NMR detection with (ii) microfluidics and (iii) advanced hyperpolarization methods. The pioneering SingleCellQNMR project is based on my recently developed NMR technology for microscopic sample volumes using nitrogen-vacancy (NV) centers in diamond. These defects act as atomic-sized magnetic quantum sensors and are the ideal tool to detect NMR signals from smallest volumes, such as from a single cell. A second-generation quantum diamond spectrometer with integrated hyperpolarization capabilities will be developed here to match the high technical requirements for single-cell studies. It will be a new transformative tool to study: a) Single-cell metabolomics. The high molecular specificity of NV-NMR will be used to analyse and quantify metabolites on the single-cell level noninvasively. Cells will be exposed to external stimuli such as drugs and their individual metabolic response will be monitored over time. b) Single-cell water diffusion and relaxation-based contrast. Water diffusion and proton relaxation will be measured on a single-cell level. This will allow for the investigation of microstructures and to record data for validating current models of magnetic resonance imaging contrast. The SingleCellQNMR project will develop a ground-breaking non-invasive tool and provide first results in a new era of single-cell studies.

Germany

2025-10-01