Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

Abstract

Ambient ionization imaging mass spectrometry is uniquely suited for detailed spatially-resolved chemical characterization of biological samples in their native environment. However, the spatial resolution attainable using existing approaches is limited by the ion transfer efficiency from the ionization region into the mass spectrometer. Here we present a first study of ambient imaging of biological samples using nanospray desorption ionization (nano-DESI). Nano-DESI is a new ambient pressure ionization technique that uses minute amounts of solvent confined between two capillaries comprising the nano-DESI probe and the solid analyte for controlled desorption of molecules present on the substrate followed by ionization through self-aspirating nanospray. We demonstrate highly sensitive spatially resolved analysis of tissue samples without sample preparation. Our first proof-of-principle experiments indicate the potential of nano-DESI for ambient imaging with a spatial resolution of better than 12 μm. The significant improvement of the spatial resolution offered by nano-DESI imaging combined with high detection efficiency will enable new imaging mass spectrometry applications in clinical diagnostics, drug discovery, molecular biology, and biochemistry.

Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

“…Now, desorption electrospray ionization mass spectrometry (DESI-MS) (11), as well as related MS-imaging methods (12), offer the possibility of incorporating lipid information into tumor diagnostics. DESI is one of a recently developed group of ionization techniques in MS in which samples are examined in the ambient environment with minimal pretreatment (13)(14)(15)(16)(17). Using DESI, direct lipid analysis from biological samples such as tissue sections can be performed rapidly and routinely.…”

Ambient Molecular Analysis of Biological Tissue Using Low-Energy, Femtosecond Laser Vaporization and Nanospray Postionization Mass Spectrometry

“…Molecular profiling and imaging of animal tissue samples with minimal sample preparation have been demonstrated by several ambient ionization MS techniques, including DESI [9,25,61], nano-DESI [10,22], IR-MALDESI [11,62], and LAESI [12,63]. To investigate the possibility of using LEMS for the analysis of animal samples, mouse brain was chosen in our analysis.…”

“…Plasma-based techniques like direct analysis in real time (DART) or low temperature plasma (LTP) are ideal for the analysis of volatile analytes [17,18], and have been used to explore the hydrocarbon profile of live flies [7] as well as the metabolite distribution of a chili fruit [19]. Liquid extraction sampling techniques, including liquid microjunction surface sampling probe (LMJ-SSP) [8], liquid extraction surface analysis (LESA) [20], nanospray desorption ionization (nano-DESI) [21], and single-probe [16], are powerful tools to study the distribution of lipids, drugs, and metabolites in animal tissues [8,20,22], bacterial colonies [23], and single cells [16], but require careful design and optimization to manipulate the liquid sampling probe because of the physical and chemical heterogeneity of the sample in question. The spraybased technique desorption electrospray ionization (DESI) has high sensitivity, histologic compatibility, and lateral analysis capability [9,24], but routine DESI has a spatial resolution of 200 μm, although a resolution of 35 μm has been demonstrated through careful optimization of the spray operating parameters [25], and the analysis is limited to compounds that are ionized by ESI-like processes [5].…”

Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions

“…However, these methods require extensive sample preparation, such as the application of matrix molecules to the sample surface, and a vacuum sampling environment, which could introduce artifacts to the data obtained. Ambient techniques such as desorption electrospray ionization (DESI) MS 5 , laser ablation electrospray ionization (LAESI) MS 6 , and nano-DESI MS 7 are capable of MSI of samples with little to no prior preparation under the ambient environment, which is able to produce MS images that potentially reflect the sample in its most native state. However, most of these techniques generally lack the high spatial resolution and detection sensitivity compared with the non-ambient techniques, with experiments typically conducted at around 150 μm per pixel 8 .…”