مقاله انگلیسی رایگان در مورد طیف سنجی جرمی در پاتولوژی – الزویر ۲۰۱۸

Mass spectrometric (MS) techniques are applied in various areas of medical diagnostics. For the detection of microbiological germs and genetic mutations, MS is a method used in routine. Since MS also allows the analysis of proteins and peptides, it seems an ideal candidate to supplement histopatholological diagnostics. Matrixassisted laser desorption/ionization time-of-flight Imaging MS links molecular analysis of numerous analytes with morphological information about their spatial distribution in cells or tissues. Herein, we review principle MS techniques as well as potential applications in pathology and discuss our vision for a future workflow.

Introduction

Mass spectrometric (MS) techniques are applied in various areas of medical diagnostics. In microbiological germ detection, MS is a routine diagnostic method since the last years [17,58]. Similarly, this technique has been introduced into toxicology [51], as well as in forensic medicine [6,28]. For the analysis of DNA, this technique allows the detection of several hunrdred different mutations and is therefore applied in molecular pathology already today [41,45]. However, as the identification of mutations by MS is based on prior PCR amplification, the method is most suitable for the detection of hotspot mutations and there are limitations when it comes to the identification of complex mutations or genetic aberrations. As MS also allows the analysis of proteins [68] and peptides [40,48], it seems an ideal candidate for histopatholological diagnostics which strongly relies on the detection of proteins and peptides by immunohistochemical (IHC) methods [71]. An advantage of MS as compared to IHC, is the detection of numerous proteins or peptides without the need for target-specific antibodies [56]. On the other hand, the identification of the detected ion peaks might be a challenge. MS can be applied in the profiling mode where a region of a tissue section has been chosen for application of the laser which ionizes the proteins or peptides or in the imaging mode, where numerous proteins or peptides can be localized in a given tissue section [2]. Furthermore, other chemical classes can be detected in tissue such as lipids or phospholopids [14,31,39,70], carbohydrates and glycoconjugates [37], exogenous or endogenous small molecules, especially molecules playing a role in drug metabolism [34,50,65] and nucleic acids [38,57]. Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) Imaging MS (MALDI-IMS), first described by Caprioli et al. in 1997 [9], links molecular analysis of numerous analytes with morphological information about their spatial distribution in cells or tissues [7,12,22,63] and provides unbiased visualization of the arrangement of biomolecules [29]. The information contained in tissues cannot be replaced by investigation of serum or blood [67]. Therefore, pathology is not only a large field of medical research but also a basis for diagnostics of various diseases and treatment decisions.