Abstract
Many studies focused on the discovery of novel biomarkers for the diagnosis and treatment of disease states are facilitated by mass spectrometry-based technology. HPLC coupled to mass spectrometry is widely used; miniaturization of this technique using nano-liquid chromatography (LC)-mass spectrometry (MS) usually results in better sensitivity, but is associated with limited repeatability. The recent introduction of chip-based technology has significantly improved the stability of nano-LC-MS, but no substantial studies to verify this have been performed. To evaluate the temporal repeatability of chip-based nano-LC-MS analyses, N-glycans released from a serum sample were repeatedly analyzed using nLC-PGC-chip-TOF-MS on three non-consecutive days. With an average inter-day coefficient of variation of 4 %, determined on log10-transformed integrals, the repeatability of the system is very high. Overall, chip-based nano-LC-MS appears to be a highly stable technology, which is suitable for the profiling of large numbers of clinical samples for biomarker discovery.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, Feuer E, de Koning H (2009) Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst 101(6):374–383
Ross JS, Hatzis C, Symmans WF, Pusztai L, Hortobagyi GN (2008) Commercialized multigene predictors of clinical outcome for breast cancer. Oncologist 13(5):477–493
Fine BM, Amler L (2009) Predictive biomarkers in the development of oncology drugs: a therapeutic industry perspective. Clin Pharmacol Ther 85(5):535–538
Furihata T, Sawada T, Kita J, Iso Y, Kato M, Rokkaku K, Shimoda M, Kubota K (2008) Serum alpha-fetoprotein level per tumor volume reflects prognosis in patients with hepatocellular carcinoma after curative hepatectomy. Hepatogastroenterology 55(86–87):1705–1709
Ju W, Smith S, Kretzler M (2012) Genomic biomarkers for chronic kidney disease. Transl Res 159(4):290–302
Taguchi A, Politi K, Pitteri SJ, Lockwood WW, Faca VM, Kelly-Spratt K, Wong CH, Zhang Q, Chin A, Park KS, Goodman G, Gazdar AF, Sage J, Dinulescu DM, Kucherlapati R, Depinho RA, Kemp CJ, Varmus HE, Hanash SM (2011) Lung cancer signatures in plasma based on proteome profiling of mouse tumor models. Cancer Cell 20(3):289–299
Mishur RJ, Rea SL (2012) Applications of mass spectrometry to metabolomics and metabonomics: detection of biomarkers of aging and of age-related diseases. Mass Spectrom Rev 31(1):70–95
Adamczyk B, Tharmalingam T, Rudd PM (2012) Glycans as cancer biomarkers. Biochim Biophys Acta 1820(9):1347–1353
Lebrilla CB, An HJ (2009) The prospects of glycan biomarkers for the diagnosis of diseases. Mol Biosyst 5(1):17–20
Chu CS, Ninonuevo MR, Clowers BH, Perkins PD, An HJ, Yin H, Killeen K, Miyamoto S, Grimm R, Lebrilla CB (2009) Profile of native N-linked glycan structures from human serum using high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. Proteomics 9(7):1939–1951
Aldredge D, An HJ, Tang N, Waddell K, Lebrilla CB (2012) Annotation of a serum N-glycan library for rapid identification of structures. J Proteome Res 11(3):1958–1968
Alley WR Jr, Madera M, Mechref Y, Novotny MV (2010) Chip-based reversed-phase liquid chromatography-mass spectrometry of permethylated N-linked glycans: a potential methodology for cancer-biomarker discovery. Anal Chem 82(12):5095–5106
Ruhaak LR, Miyamoto S, Kelly K, Lebrilla CB (2012) N-Glycan profiling of dried blood spots. Anal Chem 84(1):396–402
Kocher T, Pichler P, Swart R, Mechtler K (2011) Quality control in LC-MS/MS. Proteomics 11(6):1026–1030
Kronewitter SR, de Leoz ML, Peacock KS, McBride KR, An HJ, Miyamoto S, Leiserowitz GS, Lebrilla CB (2010) Human serum processing and analysis methods for rapid and reproducible N-glycan mass profiling. J Proteome Res 9(10):4952–4959
Hua S, An HJ, Ozcan S, Ro GS, Soares S, DeVere-White R, Lebrilla CB (2011) Comprehensive native glycan profiling with isomer separation and quantitation for the discovery of cancer biomarkers. Analyst 136(18):3663–3671
Kronewitter SR, An HJ, de Leoz ML, Lebrilla CB, Miyamoto S, Leiserowitz GS (2009) The development of retrosynthetic glycan libraries to profile and classify the human serum N-linked glycome. Proteomics 9(11):2986–2994
Ruhaak LR, Deelder AM, Wuhrer M (2009) Oligosaccharide analysis by graphitized carbon liquid chromatography-mass spectrometry. Anal Bioanal Chem 394(1):163–174
Gast MC, van Gils CH, Wessels LF, Harris N, Bonfrer JM, Rutgers EJ, Schellens JH, Beijnen JH (2009) Influence of sample storage duration on serum protein profiles assessed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS). Clin Chem Lab Med 47(6):694–705
Acknowledgments
The authors are thankful for the funding provided by the National Institutes of Health (R21 CA135240, HD061923, HD059127, R01 GM049077, and UL1 TR 000002), the Department of Defense (CDMRP LCRP W81XWH1010635), the Tobacco Related Disease Research Program, and the LUNGevity Foundation.
Conflict of interest
The authors have declared no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 1004 kb)
Rights and permissions
About this article
Cite this article
Ruhaak, L.R., Taylor, S.L., Miyamoto, S. et al. Chip-based nLC-TOF-MS is a highly stable technology for large-scale high-throughput analyses. Anal Bioanal Chem 405, 4953–4958 (2013). https://doi.org/10.1007/s00216-013-6908-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-013-6908-z