We report the coupling of a hybrid ionization source, matrix-assisted laser desorption electrospray ionization (MALDESI), to a Fourier transform-ion cyclotron resonance mass spectrometer (FT-ICR MS). The details of the source design and initial data are presented. Analysis of peptides and proteins ranging from 1 to 8.6 kDa resulted in high resolving power single-acquisition FT-ICR mass spectra with average charge-states highly correlated to those obtained by nanoESI, thus, providing strong evidence that the ESI process dictates the observed charge-state distribution. Importantly, unlike the recently introduced electrospray assisted laser desorption ionization (ELDI) source reported by Shiea and coworkers [1,2], the data we have obtained to date rely on the use of an organic acid matrix. The results presented herein provide insight into the charging mechanism of this emerging ionization approach, while also expanding the utility of FT-ICR MS for top-down protein and complex mixture analysis. T he field of mass spectrometry has grown tremendously over the past century due in large part to the continued development of more powerful ionization techniques, mass analyzer technologies, and ion dissociation techniques. New ionization techniques inherently increase the breadth of applications amenable to mass spectrometry, thereby driving the discovery, development, implementation, and refinement of mass analyzers and ion dissociation methods. The advent of electrospray ionization (ESI) [3] and matrixassisted laser desorption ionization (MALDI) [4,5] resulted in a paradigm shift in the biological sciences whereby intact biomacromolecules could be ionized and detected by mass spectrometry.The benefits of direct analysis of samples under ambient conditions with minimal or no sample pretreatment has led to the development of a wide range of novel ionization methods with potentially extraordinary impact in numerous fields (e.g., environmental, forensics, material science, biomedical). These include fused-droplet electrospray ionization (FD-ESI) [6], laser desorption atmospheric pressure chemical ionization (LD-APCI) [7], desorption electrospray ionization (DESI) [8], direct analysis in real time (DART) [9], atmospheric-pressure solids analysis probe (ASAP) [10], and electrospray-assisted laser desorption/ionization (ELDI) [1,2]. Interestingly, modern high-performance mass analyzers are largely based on hybrid technology (e.g., coupling of linear ion trap with a Fourier transform mass spectrometer [11]) and, similarly, so are these new ionization techniques.Electrospray ionization is inherently well-suited for FT-ICR MS due to the inverse relationship between cyclotron frequency and m/z [12]. Because cyclotron frequency dictates mass resolving power, mass accuracy, limits of detection, and top-down tandem MS efficiencies, the multiple charging (lower m/z) afforded by ESI provides significant advantages [13]. Matrixassisted laser desorption ionization (MALDI) can also be coupled to FT-ICR MS where it can be a very powerful tec...

Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo lipid synthesis and glutaminolysis. These alterations are pivotal to the development and maintenance of the malignant phenotype of cancer cells in unfavorable tumor microenvironment or metastatic sites. Although mitochondrial fatty acid β-oxidation (FAO) is a primary bioenergetic source, it has not been generally recognized as part of the metabolic landscape of cancer. The last few years, however, have seen a dramatic change in the view of cancer relevance of the FAO pathway. Many recent studies have provided significant evidence to support a "lipolytic phenotype" of cancer. FAO, like other well-defined metabolic pathways involved in cancer, is dysregulated in diverse human malignancies. Cancer cells rely on FAO for proliferation, survival, stemness, drug resistance, and metastatic progression. FAO is also reprogrammed in cancer-associated immune and other host cells, which may contribute to immune suppression and tumor-promoting microenvironment. This article reviews and puts into context our current understanding of multi-faceted roles of FAO in oncogenesis as well as anti-cancer therapeutic opportunities posed by the FAO pathway.

The TripleTOF 5600 System, a hybrid triple quadrupole time-of-flight mass spectrometer, was evaluated to explore the key figures of merit in generating peptide and protein identifications which included spectral acquisition rates, data quality, proteome coverage, and biological depth. Employing a Saccharomyces cerevisiae tryptic digest, careful consideration of several performance features demonstrated that the speed of the TripleTOF contributed most to the resultant data. The TripleTOF system was operated with 8, 20, and 50 MS/MS events in an effort to compare to other MS technologies and to demonstrate the abilities of the instrument platform.

C-terminal brain (B-type) natriuretic peptide (BNP)-biomarkers ͉ electrospray ionization ͉ Fourier transform-ion cyclotron resonance MS ͉ immunoaffinity purification ͉ targeted proteomics

Biomarker discovery and proteomics have become synonymous with mass spectrometry in recent years. Although this conflation is an injustice to the many essential biomolecular techniques widely used in biomarker-discovery platforms, it underscores the power and potential of contemporary mass spectrometry. Numerous novel and powerful technologies have been developed around mass spectrometry, proteomics, and biomarker discovery over the past 20 years to globally study complex proteomes (e.g., plasma). However, very few large-scale longitudinal studies have been carried out using these platforms to establish the analytical variability relative to true biological variability. The purpose of this review is not to cover exhaustively the applications of mass spectrometry to biomarker discovery, but rather to discuss the analytical methods and strategies that have been developed for mass spectrometry–based biomarker-discovery platforms and to place them in the context of the many challenges and opportunities yet to be addressed.