Desorption Electrospray Ionization Mass Spectrometry Imaging: Recent Developments and Perspectives

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is an ambient ionization MS method utilized in over 730 peer-reviewed manuscripts. In this technique, a highly charged aerosol of microdroplets is sprayed onto a surface, desorbing and ionizing molecules which are then analyzed by MS. Since samples are analyzed in their native conditions with minimal to no sample preparation (e.g. without the need for separation or an organic matrix), chemicals, drugs, metabolites and lipids are rapidly detected and mapped in diverse types of samples. We focus on three recent DESI-MSI developments: (1) intraoperative brain cancer diagnostics, (2) developmental biology, and (3) high-throughput chemical reaction screening. For intraoperative brain cancer diagnostics, DESI-MS is being used in operating rooms for rapid tissue biopsy smear analysis to screen for diagnostic lipids and oncometabolites indicative of tumor type (e.g. glioma), grade and extent of tumor infiltration at surgical margins. Recently, isocitrate dehydrogenase (IDH) mutation status was determined intraoperatively by DESI in gliomas, offering new tumor management options which may impact extent of resection goals. In developmental biology, DESI-MSI was applied to whole body 2D and 3D swine fetus cryosections, and a range of lipids and metabolites specific to particular organs were spatially mapped and related to organogenesis. Finally, an autonomous system for high-throughput chemical reaction screening by DESI-MSI is an ongoing effort funded by the Defense Advanced Research Projects Agency (DARPA). This system takes advantage of the fact that chemical reactions are accelerated in DESI microdroplets to read over 1,000 unique reaction spots/hour and to explore the high dimensional chemical reaction space. To accomplish that, DESI-MS is integrated with four other commercial instruments all under computer control (a robotic pipetting robot, a robotic arm, a plate hoteling system and a precision solvent delivery system). In addition, future directions and perspectives for DESI-MSI will be presented.