Mini-Review

Experimental Methods in Chemical Engineering: Mass Spectrometry-MS†

Accept e d Article
Patrice Perreaulta, Etienne Robertb, Gregory S. Patiencec
a
Facultad de Ingeniería Química, Universidad Autónoma de Yucatán, Periférico Norte Kilómetro 33.5,
Tablaje Catastral 13615, Chuburna de Hidalgo Inn C.P. 97203,Yucatán, México
b
Department of Mechanical Engineering, Polytechnique Montréal, C.P. 6079, Succ. CV
Montréal, H3C 3A7, QC, Canada
c
Department of Chemical Engineering, Polytechnique Montréal, C.P. 6079, Succ. CV
Montréal, H3C 3A7, QC, Canada

Preprint submitted to Canadian Journal of Chemical Engineering November 30, 2018

†
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
[10.1002/cjce.23466]

Received 12 July 2018; Revised 25 September 2018; Accepted 16 October 2018

The Canadian Journal of Chemical Engineering
This article is protected by copyright. All rights reserved
DOI 10.1002/cjce.23466

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 Abstract
Mass spectrometry identifies the atomic mass of molecules and fragments in the gas
phase. The spectrometer ionizes the molecules that then pass through an electric or
Accept e d Article
magnetic field towards a detector. The field modifies the molecule's trajectory and we
infer mass from its direction and velocity in a static field or from the stability of its path
in a dynamic field. The electric current is amplified and a mass spectrum is generated
from the location or timing of the signal from the detector, translated into a plot of the
intensity as a function of the mass-over-charge ratio. It is field deployable, measures
concentrations in real time with a temporal resolution better than 100 ms, and detection
limits of fg. However, the signal drifts with time so we have to calibrate it as frequently
as every hour. Calibrating requires multiple mixtures with varying concentrations to
map the non-linear response.
The Web of Science Core Collection indexed over 60 000 articles that refer to
MS (2016 and 2017) with applications ranging from permanent gas analysis, to
identifying protein, forensic science, and natural products. The bibliometric software
VOSViewer[1] identified four clusters of research related to MS: (1) proteomics,
proteins, plasma, and metabolomics; (2) solid phase extraction together with gas
chromatography; (3) tandem mass spectrometry and liquid chromatography; and (4)
waste water and toxicity. We expect that the technique will continue to evolve with
increased sensitivity, lower drift, and greater specificity. Miniaturization efforts should
also continue in order to develop faster field deployable instruments. This article is
protected by copyright. All rights reserved

INTRODUCTION
The basic steps of mass spectrometry (MS) begin with sample preparation, ionization,
mass filtering, and detection. MS quantifies and identifies the species molar mass and
the molar mass of fragments. High resolution mass spectrometry discriminates between
and identifies the chemical formulas of molecules with

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Accept e d Article
the same nominal mass, like N2 and CO, for example. MS also measures the
relative abundance of different compounds in a sample and quantifies changes
in concentration of targeted ions over time. Biomolecular science derives the
structure of peptides, proteins, and entire intact viruses by analyzing fragmen-
tation patterns.[2, 3, 4] This field is driving the development of new instrumental
approaches.[5]
Physical chemists developed the fundamental principle of mass spectrometry
and have been recognized for this innovation with Nobel prizes: J.J. Thomson
(Nobel prize in 1906) constructed the first mass spectrometer, and acquired
the spectra of O2 , N2 , CO, CO2 , and COCl2 ; F.W. Aston (Nobel prize in 1922)
discovered isotopes in non-radioactive elements with a velocity-based mass spec-
trometer and observed mass defects;[6, 4] R.A. Marcus (1992) explained the frag-
mentation of ions; Paul and Steinwedel developed the quadrupole mass analyzer
(Nobel prize in 1989); and, Tanaka, Karas, Bachmann, Bahr, and Hillenkamp
invented matrix-assisted laser desorption/ionization to analyze large molecules
(Nobel prize in 2002).[7, 4]

Description
Mass spectrometers first ionize target molecules into radical cations with
an odd number of electrons (Figure 1).[8] Molecules and fragments then pass
through a mass filter in which a magnetic or electric field deflects their trajectory
in proportion to the mass-to-charge ratio (m/Z): heavier ions deflect less and
highly charged ions deflect more. At the exit of the mass filter, ions are detected
in proportion to their relative abundance. We arbitrarily assign a value of
100 % to the most intense peak (base peak) and values of the other peaks are
in proportion to their intensity with respect to the base peak (Figure 2).

Ion Sources
Electron ionization (EI) was the first technique applied to fragment molecules
in the gas phase at high vacuum (0.001 Pa).[9] A heated filament generates elec-
trons that accelerate towards an anode and impact and ionize neutral atoms
in their path. Methane, for example, takes a positive charge and produces a
second electron:

CH4 + 1e− →
− CH+
4 + 2e
−
(1)
We refer to this process as hard ionization as the electrons often fragment the
molecules. EI fragments molecules in proportion to the applied energy (ioniza-
tion voltage).
Soft ionization techniques produce fewer fragments because the ions have less
excess energy. Chemical ionization (CI) was the first soft ionization technique,
followed by fast atom bombardment (FAB), then its parent liquid secondary ion-
ization (LSI), and matrix-assisted laser desorption ionization (MALDI), among
others.[10, 4] . Biomolecular chemistry applies CI: a reagent protonates the target
in the gas phase under weak vacuum at low temperature to minimize thermal
degradation. The ions generated collide producing strong acids (NH4+ from

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Accept e d Article
Ion source Mass filter Detector
Quadrupole Faraday cup
+
M+

M+
M+
Electron ionisation M+
M+

M’+
RF signal current
ion trap
sample (anode) ion extraction measurement
and focussing

M e-
e-
M
M+
Time-of-flight Electron multiplier
M M+

e - conversion
e-
e -
acceleration field-free drift dynode
anode
M+

pumping e-
paths
filament
(cathode)
heavy light
ions ions
current
measurement
E
field

Figure 1: Mass spectrometry components. Quadrupole and time-of-flight are the most com-
mon mass filters. MS manufactures may integrate both Faraday cup and electron multiplier
detectors.

Figure 2: Furfural fragmentation pattern. The measured spectra is in blue while the reference
spectra is in red. We assign the base peak 100 %.

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Accept e d Article
ammonium, or CH5+ from methane) and quasi-molecular ions 1 amu heavier
than the parent molecule. In FAB, atoms are accelerated towards a sample
on a viscous solvent matrix like glycerol and sputter-off protonated molecules.
This technique is appropriate for non-volatile, high molecular weight, or highly
polar molecules. In LSI, an ion like Cs+ is directed towards the sample, rather
than an atom like in FAB. Researchers apply FAB/LSI to compounds with a
molar mass up to 20 000 amu, but solvent matrices, like glycerol, complicate the
spectrum. In MALDI, laser pulses ablate an analyte doped crystal matrix that
ionizes large non-volatile molecules up to 300 000 amu. Atmospheric pressure
ionization (API) measures molar masses of living organisms at ambient temper-
ature and requires no sample preparation. Desorption electrospray ionization
(DESI) atomizes a stream of ionized solvent over a sample, with the extracted
portion captured via the inlet of an atmospheric pressure interface.[4, 11] Field
ionization (FI) applies 8–12 kV electric fields that generate ions from gas-phase
molecules via quantum tunnelling. It is also a soft ionization technique due to
the low excess energy, and it minimizes fragmentation.

Mass Filters
Mass analyzers separate ions on based on their mass-to-charge (m/Z) ra-
tio with static or dynamic electric and/or magnetic fields. Scanning analyzers
measure m/Z ratios sequentially, while simultaneous analyzers measures them
all at once. Performance parameters include:
• mass range (m/Z);
• acquisition frequency (mass scans per unit time);
• transmission efficiency of ions reaching the detector;
• mass accuracy (difference between theory and measurement);
• resolution (capability to discriminate ions with close m/Z values); and
• sensitivity, (C µg−1 ).[4]

∆(detector current intensity)

(2)
∆(quantity of analytes)

The quadrupole mass filter belongs to the scanning family of analyzers along
with magnetic sector instruments. Quadrupole mass analyzers (QMA) are the
least expensive and easiest to operate but have relatively low resolution. They
consist of 4 circular or hyperbolic parallel rods and separate based on the ion
trajectory stability in the space between the rods. A high frequency alternat-
ing current superimposed on a direct voltage between pairs of opposing rods
generates a dynamic electric field. In a transmission QMA filter, we chose the
field frequency to allow only ions with a narrow m/Z ratio to pass through. All
other ions have unstable trajectories and lose their charge when they eventually

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Accept e d Article
impact the rods. Within 1 min, a QMS scans the full spectra but it can measure
a single mass repeatedly in <100 ms.
Time-of-flights (TOFs) are simultaneous analyzers that assign m/Z ratios
based on the transit time of the ions to a detector after they are ionized. All ions
have equal kinetic energy after a static electric field accelerates them, but lighter
ions travel faster. They drift in a field-less flight chamber under high vacuum
and arrive at the detector at different times according to m/Z. Compared to
QMAs, TOF instruments have a somewhat lower resolution but a much higher
acquisition frequency—up to 500 full spectra per second. The also produce a
continuous spectrum.
Tandem mass spectrometers (MS×MS×. . . = MSn ) analyze high molecular
weight organic compounds by combining multiple mass filters sequentially. The
first mass filter separates the molecules of interest then fragments a subset,
which then goes to the second mass filter. Rather than tandem-MS, gas chro-
matography and liquid chromatography are coupled with an MS to separate
the constituents of complex mixtures. GC requires volatile mixtures while LC
operates with non-volatiles and thermosensitive compounds.

Detectors
Detectors generate an electrical current from the incoming ions proportion-
ately to their abundance. Point detectors count ions at a fixed location in space
either sending only a narrow m/Z range to this point (QMA) or segregating
the arriving ions in time (TOF). Array detectors count multiple m/Z ratios
simultaneously over a specific region where the mass analyzer segregates ions in
space (magnetic sector mass analyzers).
The Faraday cup is a simple point detector consisting of a metallic cup with
a small orifice open to the vacuum of the mass analyzer on the other side. It
generates a direct current when the grounded cup surface neutralizes the ion
beam. Accuracy is a function of how effective the cup prevents ion reflection
and secondary electron ejection. Cup geometry, coating, and the magnetic field
are design parameters to minimize these phenomena. Faraday cups are less
sensitive than other detectors and are best for abundant analytes. The lower
limit ranges from 50–100 ppm (1 µg g−1 ) depending on the electronics. Other
detectors can identify concentrations as low as a couple 1 ng g−1 .
Ions colliding with the surface of SEM detectors (secondary electron emis-
sion) generate secondary electrons and from the cascade effect, these electrons
also produce secondary electrons. Discrete dynodes at decreasing negative po-
tential and continuous dynodes (channeltron) with a voltage applied at the two
extremities amplify the current. The low frequency collision ions hitting the
detector surface generate a current that is amplified. SEMs scan more rapidly
than Farady detectors but are less precise. They are best suited for light ions
that generate more secondary ions due to their high speed compared to heavy
ions. Sputtering of the semiconductor-coated surface and contaminants limit
their lifetime to 1–2 y.

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Accept e d Article

Figure 3: Relative sensitivity of binary mixture of light gases in Ar measured over a period of
one month with a Hiden QIC-20 quadrupole MS.

Calibration
Instrument sensitivity depends on ionization technique, mass filtering and
detection, vacuum chamber pressure, analyte molar mass, concentration, and
on the nature of the other constituents (space charge effect). The signal varies
linearly over +− two decades. Calibrating n species requires an n − 1 sen-
sitivity hyper-surface and mixtures of 3–5 gases require hundreds of reference
mixtures.[12] For example, when the concentration of an easy-to-ionize molecule
increases in the sample, the space charge density increases in the ionization
chamber and mass filter, which decreases sensitivity of the other species. Con-
sider the sensitivity of binary mixtures of small gaseous molecules diluted with
argon (Figure 3). When we replace argon with CO2 or CH4 , which have a
larger ionization cross section, sensitivity decreases asymptotically. Sensitiv-
ity increases when replacing Ar with He and H2 , which are more difficult to
ionize.[12]
We measured the relative sensitivities (RS) during a one month period.
The carbon dioxide relative sensitivity RS was the most accurate. Increasing
the concentration of each species reduces the RS of CH4 and CO2 most.
When the ionization cross-section of the manufacturer’s reference species is
known, relative sensitivity for other species is based on their cross-sections and
scales with the raw mass spectra with species-specific factors. When instruments
express m/Z peak intensity as partial pressure, the real signal intensity is the
ratio of measured intensity (Pmeas,i ) and relative sensitivity (RSi ).[13] The mole
fraction is then:
Pmeas,i
yi = P (3)
RSi i Pmeas,i
This approach accounts for ionization under idealized conditions but ignores

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space charge effects and other species-dependent phenomena attributable to
the ion source and the detector. Even so, this simple calibration procedure is
adequate when the analytes are present in trace amounts, where concentration
varies modestly, or for qualitative analysis. Quantitative analysis requires a
model for RS as a function of species mole fraction (c.f. Figure 3), e.g., as a
polynomial, and include it in Equation 3.
We must correct the calibration equation in the case when the fragments
overlap with other analytes’ signals. For example, electron ionization of CO2
produces an m/Z ratio of 28: the high energy CO2+ radical cation decomposes
to CO+ , CO, and O+ :

CO2 + 1e− →
− CO2+ +2e− (4)

CO + O+

CO2+

CO+ + O

For mixtures of CO and CO2 , we modify the CO calibration equation to

remove the CO2 contribution (Equation 5). For complex systems, researchers
compare their spectra with the NIST database[14] , like to identify complex or-
ganic molecules,[15, 16] peptides,[17] and proteins, [18] often with a GC or LC to
separate the compounds. However, we recommend that you measure the frag-
ments: feed sequentially Ar then a mixture of Ar and the gas of interest (as
long as its molar mass is not 40 g mol−1 : We prefer Ar rather than N2 because
of air ingress through fittings at the capillary inlet) that would contribute to
the m/Z = 28 signal. Furthermore, we can quantify how much gas enters. The
spectrum must have a signal at m/Z = 28, m/Z = 32, and m/Z = 16 due to
oxygen. Air has a 28:32 ratio of about 3.8.
Pmeas,CO − X28,CO2 ∗ Pmeas,CO2
yCO = P (5)
RSCO i Pmeas,i

Applications
The Web of Science Core Collection (WoS) indexed over 60 000 documents
in 2016 and 2017 that contained ”Mass Spectrometry” in the basic search tab,
which ranks it second after x-ray diffraction as the most frequently cited tech-
nique. A bibliometric map of the top 10 000 cited articles with mass spectrome-
try among the keywords identifies four research clusters (Figure 4). The small-
est cluster relates to water analysis, pharmaceuticals, and toxicity (blue circles
on the lower right). The next smallest field relates to several MS techniques
including tandem-MS, LC-MS, and urine analysis (beige circles on the lower

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Accept e d Article
right). Mass spectrometry characterizes aerosols, by sizing particles followed by
laser ablation or thermal vaporization in time-of-flight mass spectrometers thus
characterizing the composition of particles extending down to 35 nm.[19] GCMS,
HPLC, solid phase extraction, and nanoparticle analysis form the second most
cited interlinked group. Finally, the most cited cluster includes biochemistry
and the analysis of biological fluids and biomolecules (red circles).
Among the top cited 10 000 articles, 24 % belong to analytical chemistry,
followed by biochemistry (13 %), environmental science (9 %), and molecular
biology (9 %). Chemical engineering is 20th with 232 articles. In The Cana-
dian Journal of Chemical Engineering, MS is the 8th most cited spectroscopic
method, with 50 articles mentioning it in the keywords.
Lancet Infectious Diseases and Nucleic Acids Research published the most
cited articles from 2016 and 2017. The former’s ”Emergence of Plasmid-Mediated
Colistin Resistance Mechanism MCR-1 in Animals and Human Beings in China:
A Microbiological and Molecular Biological Study” had 861 cites[20] after two
years and the latter’s ”Metabolomics Workbench: An International Repository
for Metabolomics Data and Metadata, Metabolite Standards, Protocols, Tuto-
rials and Training, and Analysis Tools” had over 700 cites.[21] The top cited
article WoS assigned to chemical engieering with 51 cites was ”Thermal Degra-
dation of CH3 NH3 PbI3 Perovskite into NH3 and CH3 I Gases Observed by Cou-
pled Thermogravimetry-Mass Spectrometry Analysis,”[22] published by Energy
& Environmental Science. The authors coupled thermal gravimetric analysis
with a quadropole MS to monitor gases evolving during the decomposition of
CH3 NH3 PbI3 . In the second most cited chemical engineering article (ranked
114th with 48 cites), the authors apply Fourier transform ion cyclotron reso-
nance mass spectrometry (FT ICR MS) to confirm that Ni2 P/SiO2 moderately
deoxygenates bio oil.[23]
In 2016 and 2017 Can. J. Chem. Eng.published 30 articles citing mass spec-
trometry. Only two articles applied MS independently from any other analyt-
ical technique to monitor gas-phase transient composition in real time like in
Figure 5.[25, 26, 27] Another article combined a homemade H2 temperature pro-
grammed reduction reactor with an MS to study Fischer-Tropsch synthesis with
a Co based catalyst on γ −Al2 O3 .[28] Three articles mention inductively coupled
plasma with MS (ICP-MS), one of which prepared mesoporous metal-CeO2 cat-
alysts for the reverse water gas shift reaction,[29] while another article studied
polyethylenimine capped copper nanoparticles to oxidatively degrade organic
pollutants for water treatment.[30] Eight articles mention HPLC electrospray
ionization-mass spectrometry but combining gas chromatography with MS is
by far the most common combination with 16 articles of the 30.

UNCERTAINTY

Limitations
The three components of a mass spectrometer are the ion source, mass filter,
and detector. We choose the ion source based on analyte composition and

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ICP MS

biological

crystal structure

biosynthesis oxidation

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adsorption

milk

9
acid

gene expression
antibiotics
inflammation

risk assessment
diagnosis bisphenol a
exposure

serum

Figure 4: MS bibliometric map.[1, 24] The size of the keyword is proportional to the number of occurrences (from 87 to 1167—Tandem MS). The
distance between keywords shows how closely topics are related. The map includes the top 100 topics.
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Figure 5: MS continuous monitoring of the effluent gas from a fluidized bed reactor—
dehydration of fructose to 5-hydroxymethyl furfural.[27] The gas composition of the feed at
t = 0 was 99.9 % (molar) Ar and 0.1 % O2 . At t = 10 min, a pump sparged a fructose-in-water
solution to the reactor. Consequently, the O2 signal dropped and the CO and CO2 signals
increased. Air leaks through fittings between the capillary and process lines so nitrogen con-
tributes to the 28 amu baseline signal, which we label as CO. During the 3 h experiment, we
sampled the quench immediately upstream of the MS take-off, which perturbs the system and
the signal: at 140 min, the oxygen signal increases simultaneously with the 28 amu, which
represents a large infiltration of air. The Ar signal drifts down from 5.8 × 10−8 at 0.5 h to
5.0 × 10−8 at 3 h. Coincidentally, the O2 signal drops from 4.8 × 10−11 to 3.4 × 10−11 .

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the phase. Mass filters determine resolution and acquisition frequency, while
the detector limits sensitivity. Commercial instruments often bundle the three
components. Furthermore, MS is almost always combined with a GC or HPLC,
which further narrows the possibilities, especially in terms of suitable mass
filters. For instance, a GC-MS requires high scan rates so TOF mass filters are
best, although the scan rate of quadrupoles is increasing (Table 1).

Analyzer Mass Resolving Detection Scan Price

range power limit rate
Quadrupole 1-1000 2000 ppb / fg 0.1 Hz $
Time of flight 4-12000 12000 pg kHz $$
Magnetic sector 1-2400 60000 fg Hz $$$$
Ion trap 50-6000 140000 fg 10 Hz $$$

Table 1: Qualitative comparison between mass filtering approaches

Most mass spectrometers have turbo-molecular or diffusion pumps that gen-

erate a high vacuum (0.001 Pa), which is important to minimize collisions be-
tween other ions and internal surfaces. For gas phase systems, the analytes pass
through a capillary (direct infusion) or a vacuum interlock (direct insertion)
to maintain a high vaccum. Electrospray ionization (ESI) and matrix-assisted
laser desorption (MALDI) volatilize condensed phases.
Electron-ionization quadrupole mass spectrometers (EI-QMS) are the most
economic, but have limited acquisition frequencies (single points in a few sec-
onds, full scans in a few minutes). When the fragment overlap is extensive,
the spectra are difficult to interpret. The resolving power of an instrument is
defined as the ratio between the mass measured (m) and the width of the peak
associated with this mass (∆m). This parameter guides choices of the three
components: QMSs are inexpensive but have low resolving power. TOFs have
high scan rate and good resolution, but since they measure all species simulta-
neously and integration time is limited, sensitivity is relatively low. Instruments
that simultaneously have high resolving power and high sensitivity are, not sur-
prisingly, the most expensive and include ion trap and magnetic sector.

Sources of Error
Contrary to many other analytical instruments, mass spectrometry reports
quantitative data terms of the molar mass of the consituents and their relative
abundance. When we want to identify the presence of an analyte in a sample,
the main error relates to assessing its mass—its resolving power. Errors with a
QMS are on the order of 0.1–0.5 amu (<0.1 %), while mass accuracy of other
mass filtering approaches are 3 orders of magnitude better (<0.002 %).
Calibration is necessary to quantify (rather than identify) mixture composi-
tions, which entails relating ionic current at the detector to the relative abun-
dance of all constituents. The intrinsic non-linearity of the ion source and mass

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filter contribute to the error particularly when the concentration of the ana-
lytes change with time or their proportions. For QMS, a change in sensitivity
to a specific mass by more than 50 % over a large concentration range is not
uncommon (Figure ??). Errors of 5 % to 7 % are possible when the MS is cal-
ibrated with several mixtures that cover the concentration range, while errors
for uncalibrated instruments are as high as 50 %[12] .
Check both single point and multivariate instruments periodically to check
drift (from hours to months). Wear of the ionization source and detector causes
the drift.

Detection Limits
The minimum amount or proportion of a substance that MS detects or quan-
tifies depends on its mass. Detection limits depend on the efficiencies to ionize,
filter, and detect a specific mass. Only high-resolution (HRMS) or tandem (MS-
MS) mass spectrometry report non-zero signals, so defining an instrument de-
tection requires identifying a signal sufficiently different from background noise
to be quantifiable.
When an MS samples a gas stream continuously, we define detection limits
in terms of the relative abundance of a constituent. EI-QMS instruments with
electron mulitplier detectors have gas phase detection limits of of 100 ppb. More
sophisticated QMS can achieve detection limits of a few ppb.
For GC-MS or LC-MS, an MS measures each peak of the analytes that
elute from the column. Detection limit expressed in terms of concentration is
of little interest since the injection volume and the flow rate of carrier fluid
varies between instruments. Rather we express detection limit in terms of the
minimum mass of a substance that must be present in the sample introduced
in the column. When coupled with adapted detectors, the mass filters detect
analytes from the pg to fg range (Table 1). Increasing the scan rate increases
the detection limit because there is less time to measure a signal for each specific
m/Z ratio. For this reason, the TOF high scanning rates have higher (poorer)
detection limits compared with other mass filters.

CONCLUSIONS

Mass spectrometry is a routine tool in many scientific fields ranging from

process monitoring to protein identification with tens of thousands of articles
published every year. An MS identifies molecules in a sample by first ionizing
them, then separating the ions and fragments based on mass over charge ratios.
However, the technique is qualtitative by nature as the ionization, separation,
and detection efficiency depend on the species and sample composition. Tan-
dem MS and coupling it with HPLC and GC increase its capability to identify
unknown analytes at the expense of speed. MS instruments are effective to moni-
tor process streams but require frequent calibration with multiple mixtures over
a wide composition range to report concentration quantitatively. Extra care
should be taken in the case of extensive fragmentation and overlapping ions.

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Mass spectrometry is now entering in a new era of increased resolution, accu-
racy, and detection capabilities, opening new possibilities, especially in the field
of proteomics, where the technique enables major contributions in structural
biology. For example, for structure determination, proteins are transferred in
the gas phase with minimal structure deformation, allowing the characteriza-
tion of their average collision cross-sections.[31] In medicine, by analyzing the
the aerosol released during electrosurgical dissection, researchers are capable of
identifying cancer cells in vivo.[32] A disposable, biocompativle handheld pen-
like mass spectrometer, the MasSpec Pen, is also being developed to identify
potential cancer biomarkers from molecules extracted from a tissue sample ex
and in vivo, using a water droplet, enabling surgeons to identify the boundary
between cancer cells and normal tissues. This tool can thus help surgeons assess
whether they fully removed cancer cells.[33] In material science, ionization time-
of-flight mass spectrometry is being used for mass spectrometry imaging (MSI).
Nanoscale resolution chemical analysis is performed via the formation of 50 nm
to 80 nm craters via laser ablation, and the sputtered material is analyzed.[34]
For decades, researchers have attempted to miniaturize these instruments for
security applications, detecting toxic compounds in transportation systems, can-
cer cells in medicine, environmental field and material science measurements,
and travelling to Mars.[9]

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