Advances in MALDI Mass Spectrometry in Clinical Diagnostic Applications

Abstract

The concept of matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was first reported in 1985. Since then, MALDI MS technologies have been evolving, and successfully used in genome, proteome, metabolome, and clinical diagnostic research. These technologies are high-throughput and sensitive. Emerging evidence has shown that they are not only useful in qualitative and quantitative analyses of proteins, but also of other types of biomolecules, such as DNA, glycans, and metabolites. Recently, parallel fragmentation monitoring (PFM), which is a method comparable to selected reaction monitoring, has been reported. This highlights the potentials of MALDI-TOF/TOF tandem MS in quantification of metabolites. Here we critically review the applications of the major MALDI MS technologies, including MALDI-TOF MS, MALDI-TOF/TOF MS, SALDI-TOF MS, MALDI-QqQ MS, and SELDI-TOF MS, to the discovery and quantification of disease biomarkers in biological specimens, especially those in plasma/serum specimens. Using SELDI-TOF MS as an example, the presence of systemic bias in biomarker discovery studies employing MALDI-TOF MS and its possible solutions are also discussed in this chapter. The concepts of MALDI, SALDI, SELDI, and PFM are complementary to each other. Theoretically, all these technologies can be combined, leading to the next generation of the MALDI MS technologies. Real applications of MALDI MS technologies in clinical diagnostics should be forthcoming.

Species identification within Acinetobacter calcoaceticus–baumannii complex using MALDI-TOF MS

“…Such instruments are usually single TOF mass analysers that do not allow for efficient structure and sequence investigation of analytes. The ABSciex 5800 instrument in our laboratory is a TOF/TOF instrument which can overcome the limitations of a single TOF mass analyser by linking two TOF mass analysers in series, making it a much more powerful tool in protein research (Ng et al, 2014). However, due to the lack of a database, bacterial identification is not readily performed with this instrument.…”

Nanomaterial-based miniaturized extraction and preconcentration techniques coupled to matrix-assisted laser desorption/ionization mass spectrometry for assaying biomolecules

“…In the past decade, several approaches (e.g., microbial culture, microscopy, biochemical tests, immunoassays, and molecular diagnostics) were used for the diagnosis of infectious diseases independently or in combination with each other [109]. Even though these methods provide accurate information about the microorganisms, they are unfortunately laborious and time consuming, as they involve the pathogen-amplification step.…”

Proteomic profiling of platelet signalling

“…There are more than 20,000 genes within the genome of which approximately 20% are involved in signaling at some level [20,21]. Although platelets are enucleated cell fragments, they still contain 3000 -6000 mRNAs, of which many are abundant and expressed including those coding for membrane GPs [11]. Many diseases are underpinned by alterations in signaling networks Expert Rev.…”

“…As platelets are enucleated, the primary focus is on the protein content of these cellular fragments. Comprehensive analysis of the platelet signaling proteome may Review therefore shed light on both hypo-and hyperthrombotic conditions through the comprehensive quantification and analysis of protein function and modification [11].…”