Micro pillar array columns; Ion mobility mass spectrometry; Proteomics; Microfluidics; Peak capacity
Abstract :
[en] Micro pillar arrays columns (mPAC) are recent nanoflow liquid chromatographic (LC) systems featuring highly ordered pillars containing an outer porous shell grafted with C18 groups. This format limits backpressure and allows the use of extremely long separation channel (up to 2 m). In this study, we evaluated the use of mPAC in combination with ion mobility mass spectrometry (IM-MS). In IM-MS, ions are separated in gas-phase based on their size and charge. mPAC was compared to two other nanoflow systems and a state-of-the-art ultra-high-pressure liquid chromatograph (UHPLC). Performances in the four dimensions of information (LC, IM, MS and intensity) were calculated to assess the multidimensional efficiency of each tested system. mPAC proved to be superior to other nanoflow systems by producing more efficient peaks regardless of the gradient time employed which resulted in higher peak capacities (386 after 240 min gradient). In combination with IM, 3 times more peaks could be separated without loss of analysis time. Although UHPLC-ESI was superior from a chromatographic point of view, its sensitivity was rather limited compared to nanoflow LCs. On average, peaks in mPAC were 45-times more intense. Finally, mPAC combined to IM prove to enhance the proteome coverage by identifying two times more peptides than nanoflow LCs and ten times more than UHPLC. As a conclusion, mPAC combined to IM seems to be a suitable platform for discovery proteomics due to its high separation capacities.
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Gstaiger, M. and R. Aebersold, Applying mass spectrometry-based proteomics to genetics, genomics and network biology. Nature Reviews Genetics, 2009. 10(9): p. 617.
Chen, C.-H.W., Review of a current role of mass spectrometry for proteome research. Analytica chimica acta, 2008. 624(1): p. 16-36.
Novakova, L., et al., High-resolution peptide separations using nano-LC at ultra-high pressure. Journal of separation science, 2013. 36(7): p. 1192-1199.
Wu, Q., et al., Recent advances on multidimensional liquid chromatography-mass spectrometry for proteomics: From qualitative to quantitative analysis-A review. Analytica chimica acta, 2012. 731: p. 1-10.
Chen, G. and B.N. Pramanik, Application of LC/MS to proteomics studies: current status and future prospects. Drug discovery today, 2009. 14(9-10): p. 465-471.
Ishihama, Y., Proteomic LC-MS systems using nanoscale liquid chromatography with tandem mass spectrometry. Journal of Chromatography A, 2005. 1067(1-2): p. 73-83.
Bilbao, A., et al., Processing strategies and software solutions for data-independent acquisition in mass spectrometry. Proteomics, 2015. 15(5-6): p. 964-980.
Mnatsakanyan, R., et al., Detecting post-translational modification signatures as potential biomarkers in clinical mass spectrometry. Expert review of proteomics, 2018. 15(6): p. 515-535.
Wright, P., et al., A review of current proteomics technologies with a survey on their widespread use in reproductive biology investigations. Theriogenology, 2012. 77(4): p. 738-765. e52.
Horvatovich, P., et al., Multidimensional chromatography coupled to mass spectrometry in analysing complex proteomics samples. Journal of separation science, 2010. 33(10): p. 1421-1437.
De Malsche, W., et al., Realization of 1× 106 theoretical plates in liquid chromatography using very long pillar array columns. Analytical chemistry, 2012. 84(3): p. 1214-1219.
Gilar, M., et al., Implications of column peak capacity on the separation of complex peptide mixtures in single-and two-dimensional high-performance liquid chromatography. Journal of chromatography A, 2004. 1061(2): p. 183-192.
Kocher, T., et al., Analysis of protein mixtures from whole-cell extracts by single-run nanoLC-MS/MS using ultralong gradients. Nature protocols, 2012. 7(5): p. 882.
Hsieh, E.J., et al., Effects of column and gradient lengths on peak capacity and peptide identification in nanoflow LC-MS/MS of complex proteomic samples. Journal of the American Society for Mass Spectrometry, 2013. 24(1): p. 148-153.
Vidova, V. and Z. Spacil, A review on mass spectrometry-based quantitative proteomics: Targeted and data independent acquisition. Analytica chimica acta, 2017. 964: p. 7-23.
Zhao, Y.-Y. and R.-C. Lin, UPLC-MSE application in disease biomarker discovery: the discoveries in proteomics to metabolomics. Chemico-biological interactions, 2014. 215: p. 7-16.
DeStefano, J.J., et al., Performance characteristics of new superficially porous particles. Journal of Chromatography A, 2012. 1258: p. 76-83.
Broeckhoven, K., D. Cabooter, and G. Desmet, Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: Intrinsic evaluation and application to a pharmaceutical test compound. Journal of pharmaceutical analysis, 2013. 3(5): p. 313-323.
Saito, Y., K. Jinno, and T. Greibrokk, Capillary columns in liquid chromatography: between conventional columns and microchips. Journal of separation science, 2004. 27(17-18): p. 1379-1390.
Wilson, S.R., et al., Nano-LC in proteomics: recent advances and approaches. Bioanalysis, 2015. 7(14): p. 1799-1815.
Vissers, J.P., Recent developments in microcolumn liquid chromatography. Journal of chromatography A, 1999. 856(1-2): p. 117-143.
Vissers, J.P., H.A. Claessens, and C.A. Cramers, Microcolumn liquid chromatography: instrumentation, detection and applications. Journal of chromatography A, 1997. 779(1-2): p. 1-28.
Shen, Y., et al., High-efficiency nanoscale liquid chromatography coupled on-line with mass spectrometry using nanoelectrospray ionization for proteomics. Analytical chemistry, 2002. 74(16): p. 4235-4249.
Karger, B.L. and P. Vouros, A Chromatographic perspective of high-performance liquid chromatography-mass spectrometry. Journal of Chromatography A, 1985. 323(1): p. 13-32.
Urban, P.L., Clarifying misconceptions about mass and concentration sensitivity. Journal of Chemical Education, 2016. 93(6): p. 984-987.
Smith, R.D., Future directions for electrospray ionization for biological analysis using mass spectrometry. Biotechniques, 2006. 41(2): p. 147-148.
Smith, R.D., Y. Shen, and K. Tang, Ultrasensitive and Quantitative Analyses from Combined Separations− Mass Spectrometry for the Characterization of Proteomes. Accounts of chemical research, 2004. 37(4): p. 269-278.
Buckenmaier, S., et al., Instrument contributions to resolution and sensitivity in ultra high performance liquid chromatography using small bore columns: comparison of diode array and triple quadrupole mass spectrometry detection. Journal of Chromatography A, 2015. 1377: p. 64-74.
Lenčo, J., et al., Conventional-Flow Liquid Chromatography-Mass Spectrometry for Exploratory Bottom-Up Proteomic Analyses. Analytical chemistry, 2018. 90(8): p. 5381-5389.
De Malsche, W., et al., Pressure-driven reverse-phase liquid chromatography separations in ordered nonporous pillar array columns. Analytical chemistry, 2007. 79(15): p. 5915-5926.
Illa, X., et al., An array of ordered pillars with retentive properties for pressure-driven liquid chromatography fabricated directly from an unmodified cyclo olefin polymer. Lab on a Chip, 2009. 9(11): p. 1511-1516.
Mogensen, K.B., et al., Pure-silica optical waveguides, fiber couplers, and high-aspect ratio submicrometer channels for electrokinetic separation devices. Electrophoresis, 2004. 25(21-22): p. 3788-3795.
De Smet, J., et al., On the optimisation of the bed porosity and the particle shape of ordered chromatographic separation media. Journal of Chromatography A, 2005. 1073(1-2): p. 43-51.
Lavrik, N.V., L. Taylor, and M. Sepaniak, Nanotechnology and chip level systems for pressure driven liquid chromatography and emerging analytical separation techniques: A review. Analytica chimica acta, 2011. 694(1-2): p. 6-20.
Malsche, W.D., H. Gardeniers, and G. Desmet, Experimental study of porous silicon shell pillars under retentive conditions. Analytical chemistry, 2008. 80(14): p. 5391-5400.
Causon, T.J. and S. Hann, Theoretical evaluation of peak capacity improvements by use of liquid chromatography combined with drift tube ion mobility-mass spectrometry. Journal of Chromatography A, 2015. 1416: p. 47-56.
Kanu, A.B., et al., Ion mobility-mass spectrometry. Journal of mass spectrometry, 2008. 43(1): p. 1-22.
Lanucara, F., et al., The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics. Nature chemistry, 2014. 6(4): p. 281.
Stow, S.M., et al., An interlaboratory evaluation of drift tube ion mobility-mass spectrometry collision cross section measurements. Analytical chemistry, 2017. 89(17): p. 9048-9055.
Gabelica, V. and E. Marklund, Fundamentals of ion mobility spectrometry. Current opinion in chemical biology, 2018. 42: p. 51-59.
Revercomb, H. and E.A. Mason, Theory of plasma chromatography/gaseous electrophoresis. Review. Analytical Chemistry, 1975. 47(7): p. 970-983.
Gabelica, V., et al., Recommendations for reporting ion mobility mass spectrometry measurements. Mass spectrometry reviews, 2019.
Hernández-Mesa, M., et al., Collision Cross Section (CCS) database: An additional measure to characterize steroids. Analytical chemistry, 2018. 90(7): p. 4616-4625.
McLean, J.A., et al., Ion mobility-mass spectrometry: a new paradigm for proteomics. International Journal of Mass Spectrometry, 2005. 240(3): p. 301-315.
Bidlingmeyer, B.A. and F.V. Warren Jr, Column efficiency measurement. Analytical Chemistry, 1984. 56(14): p. 1583A-1596A.
Causon, T.J., et al., Probing the kinetic performance limits for ion chromatography. I. Isocratic conditions for small ions. Journal of Chromatography A, 2010. 1217(31): p. 5057-5062.
Eeltink, S., et al., Optimizing the peak capacity per unit time in one-dimensional and off-line two-dimensional liquid chromatography for the separation of complex peptide samples. Journal of Chromatography A, 2009. 1216(44): p. 7368-7374.
Fountain, K.J., et al., Effects of extra-column band spreading, liquid chromatography system operating pressure, and column temperature on the performance of sub-2-μm porous particles. Journal of Chromatography A, 2009. 1216(32): p. 5979-5988.
Snyder, L.R., J.J. Kirkland, and J.L. Glajch, Practical HPLC method development. 2012: John Wiley & Sons.
Valentine, S.J., et al., Multidimensional separations of complex peptide mixtures: a combined high-performance liquid chromatography/ion mobility/time-of-flight mass spectrometry approach. International Journal of Mass Spectrometry, 2001. 212(1-3): p. 97-109.
Wang, X., et al., Peak capacity optimization of peptide separations in reversed-phase gradient elution chromatography: fixed column format. Analytical chemistry, 2006. 78(10): p. 3406-3416.
Bobaly, B., et al., Utility of a high coverage phenyl-bonding and wide-pore superficially porous particle for the analysis of monoclonal antibodies and related products. Journal of Chromatography A, 2018. 1549: p. 63-76.
Van Deemter, J., F. Zuiderweg, and A.v. Klinkenberg, Longitudinal diffusion and resistance to mass transfer as causes of nonideality in chromatography. Chemical Engineering Science, 1956. 5(6): p. 271-289.
De Pra, M., et al., Pillar-structured microchannels for on-chip liquid chromatography: Evaluation of the permeability and separation performance. Journal of separation science, 2007. 30(10): p. 1453-1460.
Sandra, K., et al., Evaluation of micro-pillar array columns (μPAC) combined with high resolution mass spectrometry for lipidomics. LC GC Spec. Issues, 2017. 30(6): p. 6-13.
Vangelooven, J. and G. Desmet, Computer aided design optimisation of microfluidic flow distributors. Journal of Chromatography A, 2010. 1217(43): p. 6724-6732.
Vangelooven, J. and G. Desmet, Theoretical optimisation of the side-wall of micropillar array columns using computational fluid dynamics. Journal of Chromatography A, 2010. 1217(52): p. 8121-8126.
Shalliker, R.A., B.S. Broyles, and G. Guiochon, Physical evidence of two wall effects in liquid chromatography. Journal of Chromatography A, 2000. 888(1-2): p. 1-12.
Ruotolo, B.T., et al., Peak capacity of ion mobility mass spectrometry:: Separation of peptides in helium buffer gas. Journal of Chromatography B, 2002. 782(1-2): p. 385-392.
Ruotolo, B.T., et al., Peak capacity of ion mobility mass spectrometry: the utility of varying drift gas polarizability for the separation of tryptic peptides. Journal of mass spectrometry, 2004. 39(4): p. 361-367.