Clathrate nanostructures for mass spectrometry

Abstract

The ability of mass spectrometry to generate intact biomolecular ions efficiently in the gas phase has led to its widespread application in metabolomics, proteomics, biological imaging, biomarker discovery and clinical assays (namely neonatal screens). Matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization have been at the forefront of these developments. However, matrix application complicates the use of MALDI for cellular, tissue, biofluid and microarray analysis and can limit the spatial resolution because of the matrix crystal size (typically more than 10 mum), sensitivity and detection of small compounds (less than 500 Da). Secondary-ion mass spectrometry has extremely high lateral resolution (100 nm) and has found biological applications although the energetic desorption/ionization is a limitation owing to molecular fragmentation. Here we introduce nanostructure-initiator mass spectrometry (NIMS), a tool for spatially defined mass analysis. NIMS uses 'initiator' molecules trapped in nanostructured surfaces or 'clathrates' to release and ionize intact molecules adsorbed on the surface. This surface responds to both ion and laser irradiation. The lateral resolution (ion-NIMS about 150 nm), sensitivity, matrix-free and reduced fragmentation of NIMS allows direct characterization of peptide microarrays, direct mass analysis of single cells, tissue imaging, and direct characterization of blood and urine.

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.…”

Charge assisted laser desorption/ionization mass spectrometry of droplets

“…With such shortcomings, the ionization step may be considered the weakest link and the bottleneck in mass spectrometry at its current stage. Therefore, more vigorous research has been devoted to the study of ion generation in recent years, resulting in several new ionization techniques such as desorption electrospray ionization (DESI) [3], atmospheric pressure photoionization (APPI) [4], laser desorption atmospheric pressure chemical ionization (LD-APCI) [5][6][7], electrospray assisted laser desorption ionization (ELDI) [8,9], laser ablation electrospray ionization (LAESI) [10], no-discharge APCI [11,12], direct analysis in real time (DART) [13], desorption atmospheric pressure chemical ionization (DAPCI) [14], laser induced acoustic desorption (LIAD) [15,16], field-induced droplet ionization (FIDI) [17], and nanostructure-initiator ionization [18]. Among the techniques cited, APPI, ELDI, LAESI, LD-APCI, and LIAD are similar in the sense that they utilize a two-step approach in which desorption and ionization occur during two separate physical processes.…”

Post-Genomics Nanotechnology Is Gaining Momentum: Nanoproteomics and Applications in Life Sciences

“…The field of nanotechnology has been associated with several proteomics applications such as phosphoproteomics/metal oxide nanoparticles, nanostructure surfaces for protein separation, and analytical detection of biomarker proteins using arrays techniques (Leitner, 2010;Nelson et al, 2009;Northen et al, 2007;Rissin et al, 2010). This merging between nanotechnology and proteomics has generated nanoproteomics, which is defined as a discipline of science involving the application of proteomics techniques aided by nanotechnology to enhance probing and evaluating protein systems (Archakov, 2007).…”