Tissue Imaging by Nanostructure-initiator Mass Spectrometry (NIMS): from Pharmacokinetics to Disease Models
Wed 8:30 AM - Track 2: Protein and Metabolite Analysis from Tissue
Oscar Yanes
The Scripps Research Institute
Oscar Yanes, Gary J Patti, #Leah Shriver, Hin-Koon Woo, Gary Siuzdak

Center for Mass Spectrometry, Scripps Research Institute, La Jolla, CA
#Department of Cell Biology, The Scripps Research Institute, La Jolla, CA
Nanostructure-initiator mass spectrometry (NIMS) is a matrix‐free mass spectrometry technology that uses a nanostructured surface to trap liquid teflon‐like polymers ('initiator'). Analytes adsorbed onto this NIMS surface are subsequently released by laser irradiation for mass analysis. In this work we demonstrate the utility of NIMS toward imaging drugs and endogenous metabolites in tissues. Brain tissue analysis showed localized clozapine and N‐desmethylclozapine from treated animals. Also, spinal cord tissue sections in a mouse model of multiple sclerosis revealed specific localization of acyl-carnitines in lesions present in the white matter, verifying previous LC-MS metabolomics analysis. NIMS has also been applied to direct biofluid analysis where ketamine and norketamine were observed from plasma and urine. Detection of xenobiotics from biofluids was made even more effective using a novel NIMS on‐surface extraction method taking advantage of the hydrophobic nature of the initiator. Linear response and limits of detection were also evaluated for xenobiotics such as methamphetamine, codeine, alprazolam, and morphine, revealing that NIMS can be used for quantitative analysis. We also 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 Na+ or Ag+ on the NIMS porous silicon surface to provide a uniform environment rich with these cationization agents. Analysis 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). 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. In addition, we used a mouse model of Smith-Lemli-Opitz syndrome (SLOS) to image the distribution of cholesterol and 7-dehydrocholesterol in brain tissue sections, revealing the accumulation of 7-dehydrocholesterol in the cerebellum. The overall results reported underscore the potential of NIMS to analyze and image chemically diverse compounds in a sensitive, simple, and rapid way from highly complex biological tissues and biofluids.