Abstract

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) emerges as a promising tool to identify the ions (small molecules) indicative of disease states from the surface of patient tissues. In TOF-SIMS analysis, an enhanced ionization of surface molecules is critical to increase the number of detected ions. Several methods have been developed to enhance ionization capability. However, how these methods improve identification of disease-related ions has not been systematically explored. Here, we present a multi-dimensional SIMS (MD-SIMS) that combines conventional TOF-SIMS and metal-assisted SIMS (MetA-SIMS). Using this approach, we analyzed cancer and adjacent normal tissues first by TOF-SIMS and subsequently by MetA-SIMS. In total, TOF- and MetA-SIMS detected 632 and 959 ions, respectively. Among them, 426 were commonly detected by both methods, while 206 and 533 were detected uniquely by TOF- and MetA-SIMS, respectively. Of the 426 commonly detected ions, 250 increased in their intensities by MetA-SIMS, whereas 176 decreased. The integrated analysis of the ions detected by the two methods resulted in an increased number of discriminatory ions leading to an enhanced separation between cancer and normal tissues. Therefore, the results show that MD-SIMS can be a useful approach to provide a comprehensive list of discriminatory ions indicative of disease states.

Highlights

  • Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used to study surface properties of specimens due to its high molecular specificity and surface sensitivity[1,2,3]

  • One section was used for hematoxylin and eosin (H&E) staining to identify cancer and adjacent normal regions, whereas the other section was used for TOF- and MetA-SIMS analyses (Fig. 1a)

  • TOF-SIMS is a promising tool to identify the secondary ions reflecting disease states at the surface of patient tissues, its use has been hampered by the limited capacity of detecting the ions

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Summary

Introduction

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used to study surface properties of specimens due to its high molecular specificity and surface sensitivity[1,2,3]. Several studies[13,14,15] have further demonstrated that submonolayer depositions of silver or gold on the surface improve the ionization of surface molecules How these methods increase the number of detected ions and thereby improve the efficiency for identifying disease-related ions has not been systematically investigated. We present a multi-dimensional TOF-SIMS (MD-SIMS) approach for effective profiling of the secondary ions from the surface of tissue samples, which can lead to an efficient identification of disease-related ions at the tissue surface This approach first uses conventional TOF-SIMS to analyze the fresh surface of the tissues, after which Au is deposited on the surface, followed by TOF-SIMS analysis (i.e., MetA-SIMS). By combining the ions detected by TOF- and MetA-SIMS, the MD-SIMS analysis produced an increased number of discriminatory ions between cancer and normal tissues, which can be used as indicators of disease states

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