Biology Reference
In-Depth Information
induced dissociation (CID) of the ion with the helium damping
gas, followed by ejection and detection of the fragment ions
[
14
,
15
]. Using quadrupole mass analyzers, tandem MS/MS
requires combinations of multiple quadrupoles such as the lin-
ear series of three quadrupoles (Q1-Q2-Q3) known as triple
quadrupole instrument. The first triple-quadrupole mass spec-
trometer was developed at Michigan State University in the late
1970s [
16
]. Q1 and Q3 act as mass filters whereas Q2, an
RF-only quadrupole, is used as a collision cell where parent ions
selected in Q1 are allowed to collide (at ~30 eV) with neutral
molecules (often He, Ar, or N at low pressure, ~10
−3
Torr),
resulting in bond breakage of the molecular ion thus generating
smaller fragments. These daughter ions are then transferred
into Q
3
where they may be filtered or fully scanned. The process
of collision-induced dissociation allowing the elucidation of the
structure of the parent ion provides an added dimension of mass
spectral information discussed below.
The principles of time-of-flight (TOF), conceptually the sim-
plest mass analyzer, were introduced in 1946 [
17
]. An early time-
of-light mass spectrometer, named the Velocitron, was reported in
1948 [
18
]. Using TOF-MS an ion's mass-to-charge ratio is deter-
mined via a time measurement. Ions are accelerated by an electric
field of known strength (1-20 kV). The velocity of the ion depends
on its mass-to-charge ratio, which can be derived by measuring the
time taken for the particle to reach the detector at a known dis-
tance in a field-free time-of-flight tube (typically 0.5-2 m) before
striking the detector. When the charged particle is accelerated into
time-of-flight tube by the voltage
U
, its potential energy (
E
p
=
qU
)
is converted to kinetic energy:
qU
= 1/2
mv
2
. Substituting
v
=
d
/
t
,
t
= [
d
/(2
U
)
1/2
](
m
/
q
)
1/2
or, since the TOF tube distance (
d
) and
the accelerating voltage (
U
) are constants related to the instrument
settings and characteristics,
t
=
k
(
m
/
q
)
1/2
.
In 1974, Fourier transform ion cyclotron resonance mass spec-
trometry (FT-ICR MS) was developed [
19
,
20
]. The theory of
cyclotron resonance was developed in the 1930s by Lawrence
(1939 Nobel Prize in Physics) [
21
]. The operating principles of an
ICR cell (a Penning trap) in trapping and detecting ions are based
on the observation that a charged particle in a spatially uniform
magnetic field experiences a Lorentz force which causes the ion
trajectory to bend such that it rotates in a plane perpendicular to
the magnetic field axis at a frequency related to its
m
/
z
value [
20
,
22
-
24
]. In a spatially uniform static magnetic field (
B
), all ions
move in circular orbits with characteristic cyclotron frequencies
that are inversely related to the
m
/
q
:
f
=
qB
/2
πm
, where
f
= cyclo-
tron frequency,
q
= ion charge,
B
=magnetic field strength and
m
= ion mass. This is more often represented in angular frequency
(ω
c
), which is related to frequency by
f
= ω
c
/2
π
, and thus ω
c
=
qB/m
.
