Hydrogen–Deuterium Exchange Desorption Electrospray Ionization Mass Spectrometry Visualizes an Acidic Tumor Microenvironment

Abstract

We report that microdroplet hydrogen−deuterium exchange (HDX) detected by desorption electrospray ionization mass spectrometry imaging (DESI-MSI) allows the measurement of the acidity of a tissue sample. The integration of HDX and DESI-MSI has been applied to visualize the acidic tumor microenvironment (TME). HDX-DESI-MSI enables the simultaneous collection of regional pH variation and its corresponding in-depth metabolomic changes. This technique is a cost-effective tool for providing insight into the pH-dependent tumor metabolism heterogeneity.

Distinguishing between Isobaric Ions Using Microdroplet Hydrogen–Deuterium Exchange Mass Spectrometry

“…Only a few microliters of methanol-water solvent suffice to desorb and ionize a wide range of metabolites within a few seconds. In other studies, we have also shown that the transient process of microdroplet HDX can be well captured by a DESI-MS system [29]. In this study, a proportion of methanol-deuterium water is used as the desorption solvent in CPSI-MS.…”

“…Urea ([2M+H] + ) and creatinine ([M+H] + ) were the most typical ones because their isotope peak intensity differences between the two groups were so obvious to be directly read out from the average mass spectra (Figure 6B). It is probably originated from the different pH environments [29].…”

“…Urea ([2M+H] + ) and creatinine ([M+H] + ) were the most typical ones bec their isotope peak intensity differences between the two groups were so obvious directly read out from the average mass spectra (Figure 6B). It is probably originated the different pH environments [29]. Because there were more HDX-generated deuterated peaks in the metabolic pro compared to the pre-HDX metabolic profile, we evaluated the performance of prin…”

Recent Advances of Ambient Mass Spectrometry Imaging and Its Applications in Lipid and Metabolite Analysis

“…The abundance of ten amino acids, four nucleotides, nucleobases, lactate and vitamin E varies in renal cell carcinomas, and normal tissue was obtained with the help of LARESI-MSI and tandem mass spectrometry. In 2021, Song et al reported a new MSI technique called hydrogendeuterium exchange DESI MSI (HDX-DESI-MSI) to detect the pH value and visualize the acidic tumor microenvironment (TME) (Figure 7B) [120]. In this work, methanol-D 2 O was used as the spray solvent of DESI and a xenograft tumor was roughly divided into three microregions with different pH values, including 6.4 ± 0.2, 6.8 ± 0.2 and 7.2 ± 0.2.…”

Visualizing the distribution of curcumin in the root of Curcuma longa via VUV-postionization mass spectrometric imaging

“…12,13 Moreover, in situ detection can display the distribution of target molecules in the whole plant tissue and reveal the transport routes of nutrients during metabolism. Generally, the sampling methods in the field of mass spectral analysis of plant ingredients mainly include desorption electrospray ionization (DESI), 14 plasma-jet, 15 and methods based on laser technology including laser ablation-dielectric barrier discharge ionization (LA-DBDI), 16 laser ablation-electrospray ionization (LA-ESI) 17 and laser desorption ionization (LDI). 18 Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has long been used in in situ detection of biological macromolecules in animal and plant tissues, such as proteins, polysaccharides, lipids, metabolites and other biological macromolecules.…”