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Impressive developments in mass spectrometry
Trends in Analytical Chemistry, Vol. 26, No. 1, 2007
Trends
Impressive developments in mass spectrometry Charles L. Wilkins The practice of mass spectrometry is one of the methods of analytical chemistry that has undergone the greatest change during the past 25 years. There are many developments that could be highlighted in a short overview such as this. However, the present article will simply concentrate on mass analysis of non-volatiles. ª 2006 Elsevier Ltd. All rights reserved. Keywords: Mass analysis; Mass spectrometry; Non-volatile
Charles L. Wilkins* Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
*
Tel.: +1 479 575 3160; Fax: +1 479 575-4049; E-mail: [email protected]
1. Introduction Numerous mass spectrometers have been developed since 1981. That topic could be, and has been, the basis of some very interesting reviews for the non-specialist [1], but this article will simply concentrate on mass analysis of non-volatiles. Mass spectrometry (MS) of non-volatile biomolecules was difficult and, in most cases, impossible in the years before TrAC began publication. In 1985, we were able to report that laser-desorption Fourier transform (FT) MS was capable of being extending to m/z 7000 [2], having bettered the previous record high mass for laser desorption of singly-charged ions of m/z 3628 [3]. Although this development was cause for hope, biomolecules examined by Wilkins and others were pretty much confined to such examples as peptides containing no more than 10 amino acids and a few other relatively undemanding lower mass compounds. Prior to that, two techniques, fast-atom bombardment (FAB) [4] and plasmadesorption MS [5], were being advocated for the more difficult non-volatiles that scientists wanted to analyze. At about this same time, Karas, Hillenkamp and coworkers were involved in investigations of the use of UV-absorbing matrices for laser desorption of non-absorbing analytes (e.g., amino acids and dipeptides) [6]. In retrospect, this was an enormously significant study, in that it served to underpin
0165-9936/$ - see front matter ª 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.trac.2006.11.010
development of one of the two major MS accomplishments of the latter part of the twentieth century – matrix-assisted laser desorption/ionization (MALDI) MS (a concept presented in the seminal paper published by the Hillenkamp group in 1987 [7]). Interestingly, this paper by the Hillenkamp group predated the first formal publication of Tanaka and co-workers on this new technique [8], research for which Tanaka later shared the 2002 Nobel Prize. This he shared with John Fenn (for his accomplishments in electrospray ion source MS (ESI)) and Kurt Wu¨thrich (for developments in biological nuclear magnetic resonance (NMR)). In any event, the significance of the MS part of the Nobel Prize is that the two winners were key players in adapting soft-ionization methods to MS that have ultimately made possible the explosion of biological MS methods being seen today. Direct consequences of these techniques are the fields of proteomics, metabolomics and lipidomics, which would be much more difficult without MALDI and ESI. 2. Upper mass limits Consider the upper mass limits common in 1983. At that time, the highest mass substance measured by MS was reported by Cotter and Tabet. They showed a spectrum of phosphazene (m.w. 3828), reproduced in Fig. 1. Today, it is not uncommon to obtain mass spectra of much higher mass substances routinely, including MALDI of proteins and synthetic polymer distributions, and even proteins included in intact bacteria, all impossible tasks 25 years ago. As an example of one of the highest resolution MS examples today, look at the 65
Trends
Trends in Analytical Chemistry, Vol. 26, No. 1, 2007
Figure 1. Spectrum of phosphazene (m.w. 3828) (Reprinted from [3] by permission of the copyright holders).
MALDI spectrum for cytochrome C obtained in our laboratory, using a 9.4 Tesla Fourier transform mass spectrometer (Fig. 2). Even though this partial spectrum shows only the molecular ion region, it is certainly clear that there has been spectacular progress in the ability to characterize proteins. There is little doubt that this capability has led directly to the development of proteomics. Even more so, the relative ease of interfacing ESI-MS with high performance liquid chromatography (HPLC) has facilitated such high-throughput applications. As
many readers will realize, this development builds directly upon the early work of Dole in the late 1960s [9,10]. It remained for John Fenn some 15 years later (1983) to publish one of his first papers on ESI-MS that presaged the enormous analytical applications of this seemingly innocuous observation that macromolecules could be volatilized by a rather straightforward procedure [11]. Applications to high-mass polymers and other substances followed [12], as did the Nobel Prize, representing the significant importance of this tool, complementary to MALDI-MS [13].
Figure 2. MALDI spectrum for cytochrome C obtained using a 9.4 Tesla Fourier transform mass spectrometer.
66
http://www.elsevier.com/locate/trac
Trends in Analytical Chemistry, Vol. 26, No. 1, 2007
Others followed up on ESIÕs numerous implications, especially the fact that ESI can produce multiple-charged ions, greatly extending the mass range of most mass spectrometers. Early adapters of this technique included McLafferty and his students who have recently been advocating ‘‘Top Down’’ proteomics [14]. In other work, those from the Marshall Laboratory have ranged as far afield as ‘‘petroleomics’’ as well as exploring the sites of ubiquitination in proteins by FTMS [15]. Thus, ESI has led to soft-ionization capabilities every bit as impressive as MALDI. It is indeed fortunate that the time for both had come at the end of the 1980s. For the entire 25 years that TrAC has been published, scientists have had available these two complementary and exceptionally empowering ionization techniques. Conservatively, we can now say that in the past 25 years the accessible mass range has been extended by a factor of almost 1000 and mass accuracies in the subppm range have been achieved for a great many applications. For the first time, it has become possible in the twenty-first century to make mass measurements sufficiently precise and accurate to begin realistically using them to solve some of the most important and difficult medical problems. It is truly a time of great scientific opportunity, made possible in part by the stupendous advancements in MS. The few brief examples that I have used to make the point that MS has come a long way were drawn from the fields of FT ion cyclotron resonance (ICR) and timeof-flight (TOF) MS. However, they could have as easily been based on the capabilities of the plethora of new mass spectrometers that continue to emerge under the impetus of metabalomics, proteomics and lipidomics, which are fields of great and increasing interest. It is certainly a stimulating and exciting time both for mass spectrometrists and those who benefit from the wealth of new information that is becoming available.
Trends
What is most interesting is that new approaches continue to be introduced. Staying with the FTMS theme, even the past few years have been the occasion for introduction of atmospheric pressure ionization (API), electron capture dissociation (ECD), and numerous new laser-based techniques just to this field. So, one should keep in mind that relatively new designs continue to be developed and that we are far from the end. I have absolutely no doubt that the developments of the next 25 years will be as surprising to us as those that have occurred during the life of TrAC. References [1] C. Brunnee, Int. J. Mass Spectrom. Ion Proc 76 (1987) 125. [2] C.L. Wilkins, D.A. Weil, C.L.C. Yang, C.F. Ijames, Anal. Chem 57 (1985) 520. [3] R.J. Cotter, J.C. Tabet, Int. J. Mass Spectrom. Ion Phys 53 (1983) 151. [4] M. Barber, R.S. Bordoli, R.D. Sedgwick, A.N. Tyler, J. Chem. Soc, Chem. Commun (1981) 325. [5] D.F. Torgerson, R.P. Skowronski, R.D. Macfarlane, Biochem. Biophys. Res. Commun 60 (1974) 616. [6] M. Karas, D. Bachmann, F. Hillenkamp, Anal. Chem 57 (1985) 2935. [7] M. Karas, D. Bachmann, U. Bahr, F. Hillenkamp, Int. J. Mass Spectrom. Ion Proc 78 (1987) 53. [8] K. Tanaka, H. Waki, Y. Ido, S. Akita, Y. Yoshida, T. Yoshida, T. Matsuo, Rapid Commun. Mass Spectrom 2 (1988) 151. [9] M. Dole, R.L. Hines, L.L. Mack, R.C. Moble, L.D. Ferguson, M.B. Alice, Macromolecules 1 (1968) 96. [10] M. Dole, L.L. Mack, R.L. Hines, R.C. Mobley, L.D. Ferguson, M.B. Alice, J. Chem. Phys 49 (1968) 2240. [11] M. Yamashita, J.B. Fenn, J. Phys. Chem 88 (1983) 4451. [12] T. Nohmi, J.B. Fenn, J. Am. Chem. Soc 114 (1992) 3241. [13] J.B. Fenn, Angew. Chem. Int. Ed. 42 (2003) 3871. [14] Y. Ge, B.G. Lawhorn, M. Elnagger, E. Strausse, J.-H. Park, T.P. Begley, F.W. McLafferty, J. Am. Chem Soc. 124 (2001) 672. [15] H.J. Cooper, J.K. Heath, E. Jaffray, R.T. Hay, T.T. Lam, A.G. Marshall, Anal. Chem 76 (2004) 6982–6988.
http://www.elsevier.com/locate/trac
67
Trends
Impressive developments in mass spectrometry Charles L. Wilkins The practice of mass spectrometry is one of the methods of analytical chemistry that has undergone the greatest change during the past 25 years. There are many developments that could be highlighted in a short overview such as this. However, the present article will simply concentrate on mass analysis of non-volatiles. ª 2006 Elsevier Ltd. All rights reserved. Keywords: Mass analysis; Mass spectrometry; Non-volatile
Charles L. Wilkins* Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
*
Tel.: +1 479 575 3160; Fax: +1 479 575-4049; E-mail: [email protected]
1. Introduction Numerous mass spectrometers have been developed since 1981. That topic could be, and has been, the basis of some very interesting reviews for the non-specialist [1], but this article will simply concentrate on mass analysis of non-volatiles. Mass spectrometry (MS) of non-volatile biomolecules was difficult and, in most cases, impossible in the years before TrAC began publication. In 1985, we were able to report that laser-desorption Fourier transform (FT) MS was capable of being extending to m/z 7000 [2], having bettered the previous record high mass for laser desorption of singly-charged ions of m/z 3628 [3]. Although this development was cause for hope, biomolecules examined by Wilkins and others were pretty much confined to such examples as peptides containing no more than 10 amino acids and a few other relatively undemanding lower mass compounds. Prior to that, two techniques, fast-atom bombardment (FAB) [4] and plasmadesorption MS [5], were being advocated for the more difficult non-volatiles that scientists wanted to analyze. At about this same time, Karas, Hillenkamp and coworkers were involved in investigations of the use of UV-absorbing matrices for laser desorption of non-absorbing analytes (e.g., amino acids and dipeptides) [6]. In retrospect, this was an enormously significant study, in that it served to underpin
0165-9936/$ - see front matter ª 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.trac.2006.11.010
development of one of the two major MS accomplishments of the latter part of the twentieth century – matrix-assisted laser desorption/ionization (MALDI) MS (a concept presented in the seminal paper published by the Hillenkamp group in 1987 [7]). Interestingly, this paper by the Hillenkamp group predated the first formal publication of Tanaka and co-workers on this new technique [8], research for which Tanaka later shared the 2002 Nobel Prize. This he shared with John Fenn (for his accomplishments in electrospray ion source MS (ESI)) and Kurt Wu¨thrich (for developments in biological nuclear magnetic resonance (NMR)). In any event, the significance of the MS part of the Nobel Prize is that the two winners were key players in adapting soft-ionization methods to MS that have ultimately made possible the explosion of biological MS methods being seen today. Direct consequences of these techniques are the fields of proteomics, metabolomics and lipidomics, which would be much more difficult without MALDI and ESI. 2. Upper mass limits Consider the upper mass limits common in 1983. At that time, the highest mass substance measured by MS was reported by Cotter and Tabet. They showed a spectrum of phosphazene (m.w. 3828), reproduced in Fig. 1. Today, it is not uncommon to obtain mass spectra of much higher mass substances routinely, including MALDI of proteins and synthetic polymer distributions, and even proteins included in intact bacteria, all impossible tasks 25 years ago. As an example of one of the highest resolution MS examples today, look at the 65
Trends
Trends in Analytical Chemistry, Vol. 26, No. 1, 2007
Figure 1. Spectrum of phosphazene (m.w. 3828) (Reprinted from [3] by permission of the copyright holders).
MALDI spectrum for cytochrome C obtained in our laboratory, using a 9.4 Tesla Fourier transform mass spectrometer (Fig. 2). Even though this partial spectrum shows only the molecular ion region, it is certainly clear that there has been spectacular progress in the ability to characterize proteins. There is little doubt that this capability has led directly to the development of proteomics. Even more so, the relative ease of interfacing ESI-MS with high performance liquid chromatography (HPLC) has facilitated such high-throughput applications. As
many readers will realize, this development builds directly upon the early work of Dole in the late 1960s [9,10]. It remained for John Fenn some 15 years later (1983) to publish one of his first papers on ESI-MS that presaged the enormous analytical applications of this seemingly innocuous observation that macromolecules could be volatilized by a rather straightforward procedure [11]. Applications to high-mass polymers and other substances followed [12], as did the Nobel Prize, representing the significant importance of this tool, complementary to MALDI-MS [13].
Figure 2. MALDI spectrum for cytochrome C obtained using a 9.4 Tesla Fourier transform mass spectrometer.
66
http://www.elsevier.com/locate/trac
Trends in Analytical Chemistry, Vol. 26, No. 1, 2007
Others followed up on ESIÕs numerous implications, especially the fact that ESI can produce multiple-charged ions, greatly extending the mass range of most mass spectrometers. Early adapters of this technique included McLafferty and his students who have recently been advocating ‘‘Top Down’’ proteomics [14]. In other work, those from the Marshall Laboratory have ranged as far afield as ‘‘petroleomics’’ as well as exploring the sites of ubiquitination in proteins by FTMS [15]. Thus, ESI has led to soft-ionization capabilities every bit as impressive as MALDI. It is indeed fortunate that the time for both had come at the end of the 1980s. For the entire 25 years that TrAC has been published, scientists have had available these two complementary and exceptionally empowering ionization techniques. Conservatively, we can now say that in the past 25 years the accessible mass range has been extended by a factor of almost 1000 and mass accuracies in the subppm range have been achieved for a great many applications. For the first time, it has become possible in the twenty-first century to make mass measurements sufficiently precise and accurate to begin realistically using them to solve some of the most important and difficult medical problems. It is truly a time of great scientific opportunity, made possible in part by the stupendous advancements in MS. The few brief examples that I have used to make the point that MS has come a long way were drawn from the fields of FT ion cyclotron resonance (ICR) and timeof-flight (TOF) MS. However, they could have as easily been based on the capabilities of the plethora of new mass spectrometers that continue to emerge under the impetus of metabalomics, proteomics and lipidomics, which are fields of great and increasing interest. It is certainly a stimulating and exciting time both for mass spectrometrists and those who benefit from the wealth of new information that is becoming available.
Trends
What is most interesting is that new approaches continue to be introduced. Staying with the FTMS theme, even the past few years have been the occasion for introduction of atmospheric pressure ionization (API), electron capture dissociation (ECD), and numerous new laser-based techniques just to this field. So, one should keep in mind that relatively new designs continue to be developed and that we are far from the end. I have absolutely no doubt that the developments of the next 25 years will be as surprising to us as those that have occurred during the life of TrAC. References [1] C. Brunnee, Int. J. Mass Spectrom. Ion Proc 76 (1987) 125. [2] C.L. Wilkins, D.A. Weil, C.L.C. Yang, C.F. Ijames, Anal. Chem 57 (1985) 520. [3] R.J. Cotter, J.C. Tabet, Int. J. Mass Spectrom. Ion Phys 53 (1983) 151. [4] M. Barber, R.S. Bordoli, R.D. Sedgwick, A.N. Tyler, J. Chem. Soc, Chem. Commun (1981) 325. [5] D.F. Torgerson, R.P. Skowronski, R.D. Macfarlane, Biochem. Biophys. Res. Commun 60 (1974) 616. [6] M. Karas, D. Bachmann, F. Hillenkamp, Anal. Chem 57 (1985) 2935. [7] M. Karas, D. Bachmann, U. Bahr, F. Hillenkamp, Int. J. Mass Spectrom. Ion Proc 78 (1987) 53. [8] K. Tanaka, H. Waki, Y. Ido, S. Akita, Y. Yoshida, T. Yoshida, T. Matsuo, Rapid Commun. Mass Spectrom 2 (1988) 151. [9] M. Dole, R.L. Hines, L.L. Mack, R.C. Moble, L.D. Ferguson, M.B. Alice, Macromolecules 1 (1968) 96. [10] M. Dole, L.L. Mack, R.L. Hines, R.C. Mobley, L.D. Ferguson, M.B. Alice, J. Chem. Phys 49 (1968) 2240. [11] M. Yamashita, J.B. Fenn, J. Phys. Chem 88 (1983) 4451. [12] T. Nohmi, J.B. Fenn, J. Am. Chem. Soc 114 (1992) 3241. [13] J.B. Fenn, Angew. Chem. Int. Ed. 42 (2003) 3871. [14] Y. Ge, B.G. Lawhorn, M. Elnagger, E. Strausse, J.-H. Park, T.P. Begley, F.W. McLafferty, J. Am. Chem Soc. 124 (2001) 672. [15] H.J. Cooper, J.K. Heath, E. Jaffray, R.T. Hay, T.T. Lam, A.G. Marshall, Anal. Chem 76 (2004) 6982–6988.
http://www.elsevier.com/locate/trac
67