Air Flow-Assisted Ionization Imaging Mass Spectrometry Method for Easy Whole-Body Molecular Imaging under Ambient Conditions

Abstract

Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-toimplement, whole-body IMS method was developed with air flow-assisted ionization in a desorption electrospray ionization mode. The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division, or matrix deposition. Moreover, the signal levels were improved, and the spatial assignment errors were eliminated; thus, high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs and predicting possible tumor spectrum, pharmacological activity, and potential toxicity of drug candidates.

Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques

“…39 Furthermore, improved transfer of secondary droplets into a mass spectrometer inlet may be achieved using air-flow-assisted DESI (AFADESI). 40 Fernandez and co-workers reported additional improvements in DESI imaging sensitivity by coupling DESI with a differential mobility filter, which resulted in a 10-fold increase in the signal-to-noise ratio. 41 DESI and its variants have been used for imaging tissue sections, 42,43 imprints of plant tissues 44 and microbial communities, 45 fingerprints, 5 mineral surfaces, 46 and other.…”

“…147 More recently, DESI SRM was used for imaging drug penetration into skin, 148 and AFADESI MRM experiments provided information on the spatial localization of an antitumor drug. 40 Meanwhile, LESA MS/MS experiments performed in MRM mode have been used for imaging drugs in tissue sections with a spatial resolution of ~1 mm. 97 Key findings from these studies will be discussed in the next sections.…”

Development of Non-proximate Probe Electrospray Ionization for Real-Time Analysis of Living Animal

“…As previously reported, appropriate gas ow can assist the ion transfer. 16,17) en, to facilitate the effective uptake of ions into the original ion inlet of the mass spectrometer, it was necessary to attach a bespoke adaptor to an additional diaphragm pump. is modi cation made it possible for the ion sampling ori ce to be placed immediately next to large living animals, which would otherwise be too large to be placed inside the ionization chamber of a conventional MS system.…”

Development and validation of a liquid chromatography–tandem mass spectroscopy method for simultaneous determination of (+)-(13aS)-deoxytylophorinine and its pharmacologically active 3-O-desmethyl metabolite in rat plasma

“…Bioanalytical assays for CAT qualification by LC-MS/MS in mouse plasma or rat tissues were reported [14,15]. However, in the assays, neither report entirely validated LC-MS/MS method nor did they support the determination of S-4.…”