Direct Infusion Mass Spectrometry for Metabolomic Phenotyping of Diseases

Abstract

Metabolomics based on direct mass spectrometry (MS) analysis, either by direct infusion or flow injection of crude sample extracts, shows a great potential for metabolic fingerprinting because of its high-throughput screening capability, wide metabolite coverage and reduced time of analysis. Considering that numerous metabolic pathways are significantly perturbed during the initiation and progression of diseases, these metabolomic tools can be used to get a deeper understanding about disease pathogenesis and discover potential biomarkers for early diagnosis. In this work, we describe the most common metabolomic platforms used in biomedical research, with special focus on strategies based on direct MS analysis. Then, a comprehensive review on the application of direct MS fingerprinting in clinical issues is provided.

Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer's disease: Amyloid beta peptides and beyond

“…Indeed, because the majority of AD clinical trials that focus on the Aβ target have failed, the need for other therapeutic approaches based on different metabolic routes is more urgent than ever . It is possible to consider metabolomics as the last step of the “‐omics” cascade, to be added to the central dogma of molecular biology (genes>transcripts>proteins>metabolites); it represents the level of organization closest to the organism's phenotype . At variance with proteomic and metallomics studies, metabolomics requires the investigation of many different components that comprise a wide variety of compound classes with very different physical and chemical properties, as well as range of concentrations .…”

Advances in mass spectrometry-based metabolomics for investigation of metabolites

“…3,84 This feature considerably shortens the total analysis time, thus minimizing the dri of sequence analysis, and improves the repeatability and accuracy among the intersamples. 9,85 In addition, subsequent data processing is also simplied because it needs no alignment of the retention time.…”

Correction to: Metabolomic Fingerprinting of Blood Samples by Direct Infusion Mass Spectrometry: Application in Alzheimer’s Disease Research

“…Therefore, it has been demonstrated that the relationship between signal intensity and metabolite concentration is generally linear at higher sample dilutions, given that the high number of ions in concentrated samples may reduce sensitivity due to ion suppression, while at higher dilutions the beneficial effect of diminished ion suppression is lost [17]. After the extraction of metabolites, direct MS fingerprinting can be accomplished by means of different instrumental configurations [5]. Direct infusion mass spectrometry (DIMS) uses a syringe pump to constantly introduce sample extracts into the mass spectrometer, while flow injection mass spectrometry (FI-MS) is based on the infusion of samples as a plug into a stream of solvent delivered by a LC pump.…”

“…Metabolomics based on direct infusion MS has demonstrated a great potential in numerous areas, such as disease phenotyping, nutritional research, food characterization and authentication, and environmental monitoring, as recently reviewed by several authors [5,7]. Nevertheless, it should be noted that special care must be taken during the optimization of these analytical tools in order to maximize metabolomic coverage, particularly with regard to sample extraction and non-targeted MS fingerprinting.…”

“…In this context, direct infusion mass spectrometry (DIMS) has emerged as a very interesting alternative with the aim to overcome these drawbacks. DIMS-based metabolomics exhibits multiple advantages, including high-throughput screening capability because of the reduced analysis time, as well as comprehensive metabolomic coverage, thanks to the lack of a previous separation step, which prevents the inherent analytical bias introduced by these selective retention mechanisms and enables the simultaneous determination of a broad range of metabolites with very different physicochemical characteristics [5]. Thus, direct MS analysis has been postulated as a suitable tool to perform a preliminary metabolomic exploration of complex samples prior to the application of orthogonal hyphenated platforms [6].…”