Microdroplet Chemistry in Accelerated Reaction Kinetics

Microdroplet chemistry exploits the distinctive environment of liquid droplets with diameters in the micrometre range to achieve reaction rates far exceeding those observed in bulk solution. Key factors include the high surface-to-volume ratio, rapid solvent evaporation, interfacial electric fields and unique solvent organisation at the air–water boundary. Confinement within a microdroplet leads to reagent enrichment and altered solvation dynamics, while charged droplets impart additional acceleration through electrostatic effects. Together, these phenomena enable bond weakening, spontaneous oxidations and ultrafast biocatalysis under ambient conditions. Applications span the rapid synthesis of nanomaterials, high-throughput reaction screening, single-cell analysis and continuous-flow chemistry, underscoring the global significance of microdroplet platforms in green synthesis, analytical science and biotechnology.

Research from Nature Portfolio

Recent studies have elucidated the fundamental drivers of accelerated kinetics at microdroplet interfaces. A computational investigation using a coarse-grained electron model demonstrated that electric fields at the surface of aqueous droplets are amplified by non-linear coupling between intramolecular and intermolecular solvent modes, reaching values tens of megavolts per centimetre stronger than in the droplet interior. This finding provides a mechanistic basis for interfacial bond activation and enhanced reactivity. In parallel, the application of microdroplet mass spectrometry to enzymatic digestion has achieved complete protein sequence coverage in under one millisecond, a dramatic reduction from the hours required in bulk-phase protocols. Finally, aerosolised fusion of metal salt and reducing-agent streams has been shown to yield gold nanoparticles and nanowires spontaneously, without external templates or added catalysts, delivering particle growth rates and yields orders of magnitude higher than conventional methods.

Microdroplet Chemistry in Accelerated Reaction Kinetics publication trend

The graph below shows the total number of articles in microdroplet chemistry in accelerated reaction kinetics across all publications each year (not limited to Nature Index journals).

Technical terms

Microdroplet: A liquid droplet with a diameter typically in the micrometre range, offering a high surface-to-volume ratio that can accelerate chemical reactions.

Air–water interface: The boundary layer between air and a water droplet where unique solvent organisation and electric fields enhance chemical reactivity.

Water radical cation (H₂O⁺·): A short-lived reactive species formed at droplet interfaces, capable of initiating oxidation by forming adducts with organic substrates.

Autoionisation: The spontaneous generation of ions (e.g., H⁺ and OH⁻) within water microdroplets due to interfacial electric fields and confinement effects.

Electrospray ionisation: A technique that produces charged microdroplets by applying a high voltage, facilitating mass spectrometric analysis and reaction acceleration.

References

1. Acceleration of reaction in charged microdroplets. Quarterly Reviews of Biophysics (2015).
2. Electrospray Ionization Mass Spectrometry: A Technique to Access the Information beyond the Molecular Weight of the Analyte. International Journal of Analytical Chemistry (2011).
3. Can electric fields drive chemistry for an aqueous microdroplet?. Nature Communications (2022).
4. Spontaneous formation of gold nanostructures in aqueous microdroplets. Nature Communications (2018).
5. High throughput reaction screening using desorption electrospray ionization mass spectrometry. Chemical Science (2018).
6. Aqueous microdroplets containing only ketones or aldehydes undergo Dakin and Baeyer–Villiger reactions. Chemical Science (2019).
7. Ultrafast enzymatic digestion of proteins by microdroplet mass spectrometry. Nature Communications (2020).
8. High yield accelerated reactions in nonvolatile microthin films: chemical derivatization for analysis of single-cell intracellular fluid. Chemical Science (2018).
9. Quantitative detection of hydrogen peroxide in rain, air, exhaled breath, and biological fluids by NMR spectroscopy. Proceedings of the National Academy of Sciences of the United States of America (2022).
10. Spontaneous Water Radical Cation Oxidation at Double Bonds in Microdroplets. Frontiers in Chemistry (2022).
11. High Throughput Experimentation Using DESI-MS to Guide Continuous-Flow Synthesis. Scientific Reports (2019).