Advances in nanospray desorption electrospray ionization (nano-DESI) mass spectrometry

Dr. Julia Laskin

James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University

Nanospray desorption electrospray ionization (nano-DESI) is an ambient ionization technique that enables label-free molecular imaging and analysis of surfaces with minimal sample pretreatment. In nano-DESI, analytes molecules are extracted from the sample into a localized liquid bridge formed between a specially-designed probe and sample surface. The extracted analytes are  subsequently  transferred to a mass spectrometer inlet and ionized by electrospray ionization. Quantification is performed by adding an internal standard to the solvent and normalizing the signals of endogenous analytes to the corresponding adduct of the standard. Spatial profiling and mass spectrometry imaging (MSI) experiments are performed by scanning the sample under the nano-DESI probe while acquiring mass spectra from different locations to generate two-dimensional molecular maps. Recent developments in nano-DESI MSI instrumentation by our group have enabled quantitative imaging of lipids, metabolites, drugs, glycans, and proteins in tissues with high sensitivity and spatial resolution down to 8-10 microns, using finely pulled capillaries. Furthermore, we have developed microfluidic nano-DESI probes and used them for both MSI and high-throughput analysis of a broad range of biological and environmental samples. To enhance the chemical specificity of nano-DESI MSI experiments, we have integrated it with ion mobility spectrometry, online photochemical derivatization of extracted analytes, and tandem mass spectrometry. These complementary approaches have been used for isomer-selective imaging of biomolecules in tissue samples, providing unique insights into complex biochemical pathways in biological systems.