Developments in FTICR-MS and Its Potential for Body Fluid Signatures

International Journal of Molecular Sciences

Simone Nicolardi²  Bogdan Bogdanov¹  André M. Deelder²  Magnus Palmblad²  Yuri E. M. van der Burgt² 

[1] PerkinElmer, San Jose Technology Center, San Jose, CA 95134, USA;Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), PO Box 9600, 2300 RC Leiden, The Netherlands;

关键词: mass spectrometry;    proteomics;    solid-phase extraction;    ultra-high resolving power;    FTICR-MS;    instrumental development;    serum;    saliva;    clinical cohort;    profiling;   

DOI  :  10.3390/ijms161126012

来源: mdpi

【 摘 要 】

Fourier transform mass spectrometry (FTMS) is the method of choice for measurements that require ultra-high resolution. The establishment of Fourier transform ion cyclotron resonance (FTICR) MS, the availability of biomolecular ionization techniques and the introduction of the Orbitrap™ mass spectrometer have widened the number of FTMS-applications enormously. One recent example involves clinical proteomics using FTICR-MS to discover and validate protein biomarker signatures in body fluids such as serum or plasma. These biological samples are highly complex in terms of the type and number of components, their concentration range, and the structural identity of each species, and thus require extensive sample cleanup and chromatographic separation procedures. Clearly, such an elaborate and multi-step sample preparation process hampers high-throughput analysis of large clinical cohorts. A final MS read-out at ultra-high resolution enables the analysis of a more complex sample and can thus simplify upfront fractionations. To this end, FTICR-MS offers superior ultra-high resolving power with accurate and precise mass-to-charge ratio (m/z) measurement of a high number of peptides and small proteins (up to 20 kDa) at isotopic resolution over a wide mass range, and furthermore includes a wide variety of fragmentation strategies to characterize protein sequence and structure, including post-translational modifications (PTMs). In our laboratory, we have successfully applied FTICR “next-generation” peptide profiles with the purpose of cancer disease classifications. Here we will review a number of developments and innovations in FTICR-MS that have resulted in robust and routine procedures aiming for ultra-high resolution signatures of clinical samples, exemplified with state-of-the-art examples for serum and saliva.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.