Visualizing life with ambient mass spectrometry

Abstract

Since the development of desorption electrospray ionization (DESI), many other ionization methods for ambient and atmospheric pressure mass spectrometry have been developed. Ambient ionization mass spectrometry has now been used for a wide variety of biological applications, including plant science, microbiology, neuroscience, and cancer pathology. Multimodal integration of atmospheric ionization sources with the other biotechnologies, as well as high performance computational methods for mass spectrometry data processing is one of the major emerging area's for ambient mass spectrometry. In this opinion article, we will highlight some of the most influential technological advances of ambient mass spectrometry in recent years and their applications to the life sciences.

Figure 1

The cycle of major ambient mass spectrometry methods discussed in this opinion article. Center: Schematic diagram of desorption electrospray ionization (DESI) source obtaining chemical information from a biological sample surface. A stream of charged micro-droplets (in red) is sprayed onto the sample surface to desorb and ionize compounds (in multiple colors), during which molecules retain in their structural intact states. Outer strips: Time frame of the major development in ambient ionization mass spectrometry methods since DESI MS was reported in 2004. The year of the first publication using the indicated ion sources are listed in the parentheses.

Figure 2

Representative DESI IMS of cancer tissue sections. (A) DESI IMS of gastric cancer tissue section showing relative ion abundances specifically observed in the regions of cancer or normal epithelial and stromal tissues. Molecular (ion) abundances are usually displayed in false colors. (B) Marginal evaluations (middle panel) of cancerous cells are made by statistical measurements using molecular data (identified as glycerophosphoserine) acquired by DESI-MS (left panel). Results of the computational assessment are compared with cancer diagnosis made by pathologists shown in optical images of H&E stained tissue sections (right panel). Figures are reproduced by permission [17].

Figure 3

Overall real-time microbial metabolomics and peptidogenomics workflow basing on tandem mass spectral analysis. Molecular information is directly fetched from the surface of microbial colonies using nanoDESI [40] or continuous flow-probe [47] as depicted in step A. The massive MS/MS (molecular fragments) data are then grouped into multiple subsets (called “molecular families”) basing on the fragmentation patterns. Each node represents an individual ion and connects to each other showing the spectral similarity between each pair (B). The MS/MS-based computational pipelines have been extensively applied to high-throughput mining of microbe-derived natural products for an instantaneous insight into the molecular classes and structural elucidation (C). The pipelines can further be utilized to connect nonribosomal peptide synthetases (NRPSs) gene clusters to the molecular families (D).

Figure 4

Schematic diagram of microscopy ambient mass spectrometry combining a nanoDESI source with an inverted fluorescence microscope (left). The photo on the right shows a real-time snapshot of the microscope-nanoDESI platform about to make MS measurement from a mouse embryo section mounted on a regular microscope slide [48].

Figure 5

Schematic diagram of REIMS-iKnife technology for real-time data collection in the operating theater using monopolar (A) or dipolar (B) electrosurgery. Evaporative products in REIMS experiment directly from patient tissues are remotely transferred via Teflon tubing into mass spectrometer. The real-time MS patterns provide surgeons an instantaneous indicator to determine tumor margins. Bipolar forceps (C) are commercially available for electrosurgical practices and are used as a REIMS ion source to generate evaporative aerosols. The figure is adapted by permission [53].