Mass Spectrometry Imaging of Lipids in Human Skin Disease Model Hidradenitis Suppurativa by Laser Desorption Ionization from Silicon Nanopost Arrays

Abstract

Neutral lipids have been implicated in a host of potentially debilitating human diseases, such as heart disease, type-2 diabetes, and metabolic syndrome. Matrix-assisted laser desorption ionization (MALDI), the method-of-choice for mass spectrometry imaging (MSI), has led to remarkable success in imaging several lipid classes from biological tissue sections. However, due to ion suppression by phospholipids, MALDI has limited ability to efficiently ionize and image neutral lipids, such as triglycerides (TGs). To help overcome this obstacle, we have utilized silicon nanopost arrays (NAPA), a matrix-free laser desorption ionization (LDI) platform. Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease of the apocrine sweat glands. The ability of NAPA to efficiently ionize lipids is exploited in the analysis of human skin samples from sufferers of HS. Ionization by LDI from NAPA allows for the detection and imaging of a number of neutral lipid species, including TGs comprised of shorter, odd-chain fatty acids, which strongly suggests an increased bacterial load within the host tissue, as well as hexosylceramides (HexCers) and galabiosyl-/lactosylceramides that appear to be correlated with the presence of HS. Our results demonstrate that NAPA-LDI-MSI is capable of imaging and potentially differentiating healthy and diseased human skin tissues based on changes in detected neutral lipid composition.

Bringing SEM and MSI Closer Than Ever Before: Visualizing Aspergillus and Pseudomonas Infection in the Rat Lungs

“…SEM analysis has been used to monitor the quality of the matrix deposition procedure [ 20 , 21 ] and its influence on the laser ablation process [ 22 ]. Fincher et al [ 23 ] used SEM as a method complementary to MALDI-MSI in their analytical study of lipids in human skin disease. They confirmed the presence of bacteria along the hair shafts on the sick surface.…”

Atherogenic index of plasma is associated with the severity of Hidradenitis Suppurativa: a case-control study

“…Gene expression of certain sphingolipids such as ceramide and sphingosine-1, that act as biologically active signaling molecules, have been implicated in the pathogenesis of the disease [23]. In a recent report, Fincher et al [24], showed an increased localized accumulation of neutral lipids in HS-infected tissue as a result of a great bacterial load in these lesions. Moreover, recurrence of the disease has been linked to the development of dermic and subcutaneous sinus tracts, and lipids rafts in plasma membranes of keratinocytes also play a role in the regulation of metabolic and proliferative activity of these cells in HS patients [25].…”

Spatially Resolved Mass Spectrometry at the Single Cell: Recent Innovations in Proteomics and Metabolomics

“… 178 Experiments by Fincher et al have shown that the sensitivity of NAPA-based LDI is in the subfemtomole range, which is significantly more sensitive than techniques involving modification of tissues after mounting on a substrate. 179 Additionally, it is theorized that understanding the effect of array variation on ion yield quantitation is far easier using the NAPA platform as rapid prototyping techniques typically can be optimized to minimize array variation. 180 Nanostructure-initiator mass spectrometry (NIMS) is another technique that utilizes nanostructured surfaces, which use porous silicon to facilitate analyte desorption by laser irradiation.…”