Nanostructure-initiator mass spectrometry: a protocol for preparing and applying NIMS surfaces for high-sensitivity mass analysis

Abstract

Nanostructure-initiator mass spectrometry (NIMS) is a new surface-based MS technique that uses a nanostructured surface to trap liquid ('initiator') compounds. Analyte materials adsorbed onto this 'clathrate' surface are subsequently released by laser irradiation for mass analysis. In this protocol, we describe the preparation of NIMS surfaces capable of producing low background and high-sensitivity mass spectrometric measurement using the initiator compound BisF17. Examples of analytes that adsorb to this surface are small molecules, drugs, lipids, carbohydrates and peptides. Typically, NIMS is used to analyze samples ranging from simple analytical standards and proteolytic digests to more complex samples such as tissues, cells and biofluids. Critical experimental considerations of NIMS are described. Specifically, NIMS sensitivity is examined as a function of pre-etch cleaning treatment, etching current density, etching time, initiator composition, sample concentration, sample deposition method and laser fluence. Typically, NIMS surface preparation can be completed in less than 2 h. Subsequent sample preparation requires 1-5 min, depending on sample deposition method. Mass spectrometric data acquisition typically takes 1-30 s per sample.

A novel laser desorption/ionization method using through hole porous alumina membranes

“…To date a number of ionization techniques that belong to SALDI have been proposed,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, ...…”

“…The techniques in the other category utilize planar solid substrates with fine structures on the uppermost surface layer as the target plate, so that the photon energies of the laser can reach analytes which are spread over and adsorbed onto the surface and achieve desorption and ionization of analytes 20, 23, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80. Desorption Ionization on Silicon (DIOS) is the representative technique in this category 46.…”

Surface analysis of lipids by mass spectrometry: More than just imaging

“…A variety of similar approaches have been described including desorption/ionization from porous silicon (DIOS) [131], nanowire-assisted laser desorption ionization (NALDI) [132], nanostructure-initiator mass spectrometry (NIMS) [133] and graphite-assisted laser desorption ionization (GALDI) [134], with the primary difference between the techniques being the type of substrate. Additionally NIMS uses a porous, nanostructured silicon substrate doped with an "initiator" molecule, typically siloxanes or silanes [133,135]. The primary advantage of these techniques compared to standard MALDI is the production of significantly fewer matrix-related ions in the resulting spectrum, greatly simplifying the detection of low mass compounds such as FFAs [136,137].…”

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

“…However, different MALDI matrices have different ionization/desorption characteristics and may not enable adequate ionization of the target analyte. More complex techniques and tools have, therefore, been developed, which include nanostructure initiator mass spectrometry (NIMS) [11,12], ionic matrices [13,14], desorption ionization from porous silicon (DIOS) [15,16], and surface-assisted laser desorption ionization [17][18][19]. Despite some successes, these methods have never been as widely used as conventional MALDI because of technical and practical limitations, some of which are particularly problematic in imaging applications.…”