NV Diamond NMR as a new method for the analysis of microdroplets in biotechnology

• Applicant: Dileep Singh, Ph.D.
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535863523

The massive reduction of sample volumes (pico- to femtoliters) by compartmentalizing reagents, enzymes and cells in microscopic emulsion droplets has recently led to the development of extremely high-throughput screening platforms. However, the small volumes of microdroplets make chemical analysis very difficult. In most cases, optical methods are used, which are based on assays that are not only limited to a few analytes but are also prone to errors due to their complexity and can therefore lead to falsified results. Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful techniques for chemical analysis. However, conventional NMR methods are unsuitable for the analysis of microdroplets due to their low intrinsic sensitivity. As part of this interdisciplinary research project, a new method based on quantum technology is therefore being developed to overcome these sensitivity problems and enable the analysis of microdroplets using NMR. For this purpose, nitrogen-vacancy centers (NV) in diamonds are used, which serve as quantum sensors for the detection of NMR signals. These atom-like systems exhibit long-lived spin states, well-defined optical transitions, and special properties: their spin states can be both optically induced and read out and coherently manipulated by irradiating resonant microwaves, enabling their use as atom-sized magnetometers for nano- to micro-scale magnetometry. As part of this project, a microtiter platform on diamonds for the positioning of microdroplets will first be developed. This is produced using methods of soft lithography or 3D printing. Subsequently, the NV-NMR setup will be characterized and optimized based on the detection of NMR signals from water droplets. Finally, as a 'proof of principle', the analysis of environmentally relevant enzymatic reactions in microdroplets is carried out. A bio-catalyzed CO2 fixation and a pollutant-free synthesis of a pharmacological raw material serve as examples here.

• DFG Programme: WBP Position