Morphology-Driven Control of Metabolite Selectivity Using Nanostructure-Initiator Mass Spectrometry

Abstract

Nanostructure-initiator mass spectrometry (NIMS) is a laser desorption/ionization analysis technique based on the vaporization of a nanostructure-trapped liquid "initiator" phase. Here we report an intriguing relationship between NIMS surface morphology and analyte selectivity. Scanning electron microscopy and spectroscopic ellipsometry were used to characterize the surface morphologies of a series of NIMS substrates generated by anodic electrochemical etching. Mass spectrometry imaging was applied to compare NIMS sensitivity of these various surfaces toward the analysis of diverse analytes. The porosity of NIMS surfaces was found to increase linearly with etching time where the pore size ranged from 4 to 12 nm with corresponding porosities estimated to be 7-70%. Surface morphology was found to significantly and selectively alter NIMS sensitivity. The small molecule (<2k Da) sensitivity was found to increase with increased porosity, whereas low porosity had the highest sensitivity for the largest molecules examined. Estimation of molecular sizes showed that this transition occurs when the pore size is <3× the maximum of molecular dimensions. While the origins of selectivity are unclear, increased signal from small molecules with increased surface area is consistent with a surface area restructuring-driven desorption/ionization process where signal intensity increases with porosity. In contrast, large molecules show highest signal for the low-porosity and small-pore-size surfaces. We attribute this to strong interactions between the initiator-coated pore structures and large molecules that hinder desorption/ionization by trapping large molecules. This finding may enable us to design NIMS surfaces with increased specificity to molecules of interest.

Quantitative Analysis of Immunosuppressive Drugs Using Tungsten Disulfide Nanosheet-Assisted Laser Desorption Ionization Mass Spectrometry

“…On the basis of the optimization process of the WS 2 -assisted LDI-MS platform, it was identified that the sensitivity is greatly influenced by the thickness of the deposited TMD material. Although many studies reported the successful analysis of biomolecules using inorganic nanomaterials as alternative matrixes, however, the analytical sensitivity that the nanomaterials can provide is a key issue for their practical applications. − In many cases, it is ambiguous to define the major factor that limits the analytical sensitivity of nanomaterials because the method of deposition is as significant as the physicochemical properties of the material itself. The microliquid dispenser inkjet system adopted in this study is capable of controlling the volume of deposition in picoliter scales with excellent uniformity.…”

“…To deal with these limitations, several types of nanomaterials such as metal nanoparticles, carbon-based nanomaterials, and silicon-based nanostructures have been investigated in LDI-MS and have demonstrated feasibility for the analysis of biomolecules including peptides, fatty acids, and pharmaceutical drugs. − However, there are several drawbacks that need to be resolved to ensure the applicability of these alternative LDI materials. For example, metal nanoparticles can be unstable in solid states after being deposited onto the target substrate and often require in situ synthesis prior to the analysis, particularly in the case of gold nanoparticles .…”

Ecosystem Fabrication (EcoFAB) Protocols for The Construction of Laboratory Ecosystems Designed to Study Plant-microbe Interactions

“…Identify metabolites based on m/z values, retention time and compound fragmentation patterns using a library of metabolite standards. NOTE: EcoFAB devices made of a 5:1 elastomer base to curing agent mixture with custom clamps (Figure 7A) are used for root stamping onto nanostructure-initiator mass spectrometry (NIMS) chips, 28,29,30 since PDMS layers can be reversely bonded to the surfaces of NIMS chips.…”

Mass Spectrometry for Single-Cell Analysis

“…Here, the targeted sample is treated with a fixed wavelength of the laser beam to accomplish the sample desorption and ionization followed by the measurement of m/z ratio of the conditioned analyte via mass spectrometry (Abdelhamid and Wu 2015;Calavia et al 2012;Cheng et al 2012). Therefore, it is necessary for the sample to absorb the specific wavelength of laser light (Etxebarria et al 2014;Gao et al 2017;Greving et al 2011). The optimized LDI-MS technique has high sensitivity and accuracy and can detect up to femtogram (fg) level.…”