Container surface adsorption loss remains a major limitation in low-input proteomics and trace bioanalysis, even when protein low-binding tubes are used. Acoustic levitation provides a promising route to eliminate solid-surface contact, but its broader analytical use has been limited by the lack of simple contactless reagent addition method and by insufficient long-term stability for conventional biochemical reaction timeframes.  

We have developed acoustic pressure guided coalescence method that enables contact-free reagent addition and 12 hour stable levitation. This allows us to explore new aspects in analytical chemistry and chemical reactions. 

https://chemrxiv.org/doi/full/10.26434/chemrxiv.15005682/v1

Stable-isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a highly selective and accurate approach for quantitative analysis in complex biological and chemical matrices. The method uses an isotopically labelled analogue of the target analyte as an internal standard. Because the labelled standard closely matches the physicochemical behaviour of the native analyte, it can compensate for variability introduced during sample preparation, extraction, chromatography, and electrospray ionisation. Quantification is typically based on the response ratio between the analyte and its corresponding stable-isotope-labelled internal standard, which improves precision and reduces the impact of matrix effects and instrument drift. When combined with appropriate calibration and method validation, stable-isotope dilution LC-MS/MS can provide high sensitivity, broad dynamic range, and strong inter-batch reproducibility. It is therefore widely used for the measurement of endogenous metabolites, drugs, biomarkers, environmental contaminants, and other analytes requiring robust and traceable quantification.

We work with clinical collaborators to develop practical methods for more sensitive and more accurate clinical quantification and investigation. 

https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004892/v1

 Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is a solution-phase method for mapping protein epitopes and characterising antigen-antibody interactions. It measures changes in backbone amide hydrogen exchange after complex formation. Regions showing reduced deuterium uptake are interpreted as directly involved in binding or stabilised by the interaction. After deuterium labelling, the protein is quenched, digested, and analysed by LC-MS to compare bound and unbound states. HDX-MS requires no covalent labelling and can provide peptide-level information on binding interfaces, conformational changes, and allosteric effects. It is widely used in antibody characterisation, therapeutic development, and biosimilar assessment.

Native mass spectrometry (native MS) analyses intact proteins and non-covalent complexes under conditions that preserve their solution-like structure and interactions. Using gentle ionisation and carefully controlled buffers, it can determine molecular mass, stoichiometry, oligomeric state, ligand binding, and complex heterogeneity. Native MS requires relatively small sample amounts and can analyse assemblies that are difficult to characterise by conventional structural methods. It is widely used for studying protein complexes, antibody-drug conjugates, membrane proteins, and biomolecular interactions.