Detection of Carbohydrates and Steroids by Cation-Enhanced Nanostructure-Initiator Mass Spectrometry (NIMS) for Biofluid Analysis and Tissue Imaging

Abstract

Nanostructure-initiator mass spectrometry (NIMS) is a highly sensitive, matrix-free technique that is well suited for biofluid analysis and imaging of biological tissues. Here we provide a new technical variation of NIMS to analyze carbohydrates and steroids, molecules that are challenging to detect with traditional mass spectrometric approaches. Analysis of carbohydrates and steroids was accomplished by spray depositing NaCl or AgNO3 on the NIMS porous silicon surface to provide a uniform environment rich with cationization agents prior to desporption of the fluorinated polymer initiator. Laser desorption/ionization of the ion-coated NIMS surface allowed for Na+ cationization of carbohydrates and Ag+ cationization of steroids. The reliability of the approach is quantitatively demonstrated with a calibration curve over the physiological range of glucose and cholesterol concentrations in human serum (1 – 200 μM). Additionally we illustrate the sensitivity of the method by showing its ability to detect carbohydrates and steroids down to the 800-amol and 100-fmol levels, respectively. The technique developed is well suited for tissue imaging of biologically significant metabolites such as sucrose and cholesterol. To highlight its applicability, we used cation-enhanced NIMS to image the distribution of sucrose in a Gerbera jamesonii flower stem and the distribution of cholesterol in a mouse brain. The flower stem and brain sections were placed directly on the ion-coated NIMS surface without further preparation and analyzed directly. The overall results reported underscore the potential of NIMS to analyze and image chemically diverse compounds that have been traditionally challenging to observe with mass spectrometry-based techniques.

Functionalized Nanoparticles and Nanostructured Surfaces for Surface-Assisted Laser Desorption/Ionization Mass Spectrometry

“…NIMS-IMS allows a direct characterization of peptide microarrays, direct mass analysis of single cells, tissue imaging, and direct characterization of blood and urine. [147][148][149][150] Liu et al demonstrated the use of a hybrid ionization approach, matrix-enhanced surface-assisted laser desorption/ionization mass spectrometry (ME-SALDI-MS), in IMS. 151,152 In ME-SALDI, the combination of MALDI with SALDI enables the successful IMS of low-mass species with improved detection sensitivity.…”

Nanostructure Initiator Mass Spectrometry for tissue imaging in metabolomics: Future prospects and perspectives

“…Therefore, the use of NIMS for tissue imaging in negative ionization mode will likely become a reality soon. NIMS surface can be further modified by coating the nanopores with cationization agents such as NaCl or AgNO 3 Adapted from reference [25] and [26], Copyright 2012, with permission from American Chemical Society and Elsevier, respectively. [25].…”

Preparation of nanostructured silicon surface for mass spectrometry analysis by an all-wet fabrication process using electroless metal deposition and metal assisted etching

“…MS analysis methods. In addition to analysis of the model peptide sample (des-Arg 9 -Bradykinin) presented in this study, other samples, such as proteins [12][13][14], peptides [1,2,7,11], polymers [15,16], tissue [17,18] and abuse drugs [19] can be analyzed using the nSi-MS platform. Investigation of various small molecules to the nanostructured silicon surface interactions are detail discussed in our recent published paper [20].…”