Colloquium: 100 years of mass spectrometry: Perspectives and future trends

Mass spectrometry (MS) is widely regarded as the most sensitive and specific general purpose analytical technique. More than a century has passed for MS since the ground-breaking work of Nobel laureate Sir Joseph John Thomson in 1913. This Colloquium aims to (1) give an historical overview of the major instrumentation achievements that have driven mass spectrometry forward in the past century, including those leading up to the initial work of Thomson, (2) provide the nonspecialist with an introduction to MS, and (3) highlight some key applications of MS and explore the current and future trends. Because of the vastness of the subject area and quality of the manifold research efforts that have been undertaken over the last 100 years, which have contributed to the foundations and subsequent advances in mass spectrometry, it should be understood that not all of the key contributions may have been included in this Colloquium. Mass spectrometry has embraced a multitude of scientific disciplines and to recognize all of the achievements is an impossible task, such has been the diverse impact of this invaluable technique. Scientific progress is usually made via the cumulative effort of a large number of researchers; the achievements reported herein are only a representation of that effort.

Figure 1

MS stages.

Figure 2

DESI (upper) and DART (lower) ionization for ambient high-throughput mass spectrometric analysis of unprepared samples (e.g., skin, bricks, urine, clothing, tissue, etc.). From [35].

Figure 3

Canal rays formed in front of the perforated cathode ($C$) in a discharge tube. $A$ is the anode. Adapted from [207].

Figure 4

Thomson’s cathode-ray deflection apparatus. Rays from the cathode ($C$) pass through a slit in the anode ($A$) and through a slit in a grounded metal plug ($B$). A voltage is applied between aluminum plates ($D$ and $E$) and a scale situated on the end of the tube measures the ray deflection. Adapted from [186].

Figure 5

Thomson’s mass spectrum of carbon monoxide (CO). From [192].

Figure 6

Parabola spectrograph result showing isotopes of ${}^{20}\mathrm{Ne}$ and ${}^{22}\mathrm{Ne}$. Adapted from [188].

Figure 7

Dempster’s 180° magnetic sector instrument. From [42].

Figure 8

Various types of tandem MS experiments depicted using CID: (a) Product ion scanning. In this experiment, the first analyzer (MS1) is set to a value that selects one specific precursor ion. The selected ion undergoes CID in the collision cell, and the resulting fragments are analyzed by the second analyzer (MS2). (b) Precursor ion scanning. This sets the second analyzer (MS2) to transmit only one specific fragment ion to the detector. (c) Neutral loss scanning. Both analyzers are scanned in a synchronized manner, so that the mass difference of ions passing through MS1 and MS2 remains constant. (d) Multiple ion monitoring. This consists of a series of short experiments in which one precursor ion and one specific fragment characteristic for that precursor are selected by MS1 and MS2, respectively. From [48].

Figure 9

Electrospray ionization process. The analyte solution is pumped through a needle to which a high voltage is applied. A Taylor cone with an excess of positive charge on its surface forms as a result of the electric field gradient between the ESI needle and the counter electrode. Charged droplets from the tip of the Taylor cone evaporate as they move toward the mass spectrometer inlet. Adapted from [29].

Figure 10

Summary time line of major advances in MS.

Figure 11

The relative precision $\Delta Q/Q$ for $Q_{EC}$-value measurements of superallowed transitions vs their publication date, where $Q$ is the measured $Q_{EC}$ value and $\Delta Q$ is its quoted uncertainty. The data encompass the superallowed transitions from ${}^{10}\mathrm{C}$, ${}^{14}\mathrm{O}$, ${}^{26}{\mathrm{Al}}^m$, ${}^{34}\mathrm{Cl}$, ${}^{38}{\mathrm{K}}^m$, ${}^{42}\mathrm{Sc}$, ${}^{46}\mathrm{V}$, ${}^{50}\mathrm{Mn}$, and ${}^{54}\mathrm{Co}$. Each point is identified by the experimental method used in the corresponding measurement: solid squares denote ($p$, $n$) reactions; open triangles (${}^3\mathrm{He}$, $t$) reactions; solid circles, two-nucleon transfer reactions ($p$, $t$) or (${}^3\mathrm{He}$, $n$); solid triangles, combined ($p$, $t$) and ($n$, $\gamma$) reactions; and solid diamonds, Penning-trap measurements. The line illustrates the decreasing trend. From [55].

Figure 12

Maps of the predicted (a) average H isotope ratios ($\delta {}^2{\mathrm{H}}_h$) and (b) average O isotope ratios ($\delta {}^{18}{\mathrm{O}}_h$) of human scalp hair across the coterminous United States. From [51].

Figure 13

Bottom-up approach (top): proteins of interest are digested in solution with an enzyme such as trypsin, and the resulting peptides are analyzed in the gas phase by mass spectrometry. Top-down approach (bottom): intact protein ions are introduced into the gas phase and are fragmented and analyzed in the mass spectrometer, yielding the molecular mass of the protein as well as protein ion fragment ladders; this information can be used to deduce the complete primary structure of the protein. Both methods make extensive use of correlation of the mass spectrometric data with protein and whole-genome sequence databases. From [30].

Figure 14

Top-down quantitative proteomics methodology for the comprehensive analysis of post-translational modifications (PTMs) in whole proteins extracted from normal and diseased tissues. The five steps include (1), (2) Sample preparation—extraction and purification. (3) Top-down quantitative MS analyses. (4) Data interpretation. Protein sequences were characterized and their PTMs detected, identified, quantified, and mapped to single amino acid residues. (5) Correlation of PTMs with disease phenotypes. From [217].

Figure 15

Overview of tissue processing to achieve a diagnosis by traditional pathological staining techniques and by DESI imaging mass spectrometry. From [46].

Figure 16

Two different approaches to imaging mass spectrometry: (a) mass spectral information is collected from an array of designated positions to reconstruct a molecular image after completion of the experiment; (b) a two-dimensional position-sensitive detector acquires $m/z$ and position information in parallel. From [119].

Figure 17

In situ mass spectrometry using a system that provides a simplified operational protocol. (a) Miniature mass spectrometer composed of two sections, a backpack section that houses the vacuum system and control electronics and hand-held head unit with an integrated low-temperature plasma (LTP) source for a geometry-independent sampling or ionization probe. (b) Multiple-stage product ion scan (MS/MS/MS) demonstrated using 100 ppm of the model compound cocaine. (c) Miniaturized desktop point-of-care mass spectrometer system coupled with ambient paper spray for medical applications. (d) MS/MS spectra of (i) $50\mathrm{ng}/\mathrm{mL}$ of amitriptyline in blood recorded with paper spray ionization. (ii) MS/MS spectra of thiabendazole on an orange peel obtained using paper spray ionization. Adapted from [73], and [109].

Figure 18

(Top) Electrospray deposition (ESD) and (bottom) soft landing (SL) of peptide ions on self-assembled monolayer (SAM) surfaces. ESD of ${\mathrm{AcA}}_{15}\mathrm{K}$ from solution results in the formation of a peptide layer dominated by the $\beta$-sheet structure, and a stable α-helical peptide layer on SAM surfaces is formed by SL. From [202].

Figure 19

Schema of REIMS instrumentation and data collection showing use with monopolar electrosurgery. Adapted from [13].