Mass Spectrometry in Systems Biology - Systems Biology: Networks, Models, and Applications - page 3

ionization (e.g., anionic lipids, peptides carrying negative charges—
phosphopeptides, etc.). Ionization of nonpolar compounds could be
promoted by formation of metal clusters (e.g., lithium adducts of tria-
cylglycerols) [10]. In global analysis of lipids, sensitivity of analysis
depends on the concentration of lipids; lipids tend to form aggregates
at higher concentration, therefore linearity of the instrument response
is obtained only at low concentration of lipids [10]. For extremely
hydrophilic compounds, such as carbohydrates, chemical derivatiza-
tion might be used for better ionization [11].

Mass Spectrometers
Several types of mass analyzers are employed in analysis of bioana-
lytes, including time-of-flight, quadrupole, quadrupole ion trap, and
ion cyclotron resonance trap. We will briefly introduce these mass
analyzers below.
Three parameters characterize the performance of the mass
analyzer [5]:

resolution or the ratio of m / z value of a bioanalyte to the width
of the m / z peak, that is, m / z /

∆ m / z ;

mass accuracy , which defines how close the measurement of the
mass is to the actual molecular weight of the bioanalyte
(expressed in parts per million, ppm); and

scan speed or how fast a mass spectrometer collects data.

Time-of-flight (TOF) analyzer determines the m / z of an ion from its
measured flight time in field-free region. Ionized molecules receive a
predetermined amount of kinetic energy from an acceleration voltage,
therefore kinetic energy

Uz , where U is the accelerating voltage and
z is charge. Therefore, the velocity of an ion is given by v

=

(2 Uz / m ) 1/2 ,
where m is the mass of the ionized molecule. In other words, for
the same distance ions with low m / z will travel faster than ions
with high m / z .
Sources that generate ions in repetitive pulses are the natural choice
for TOF analyzers (for example, MALDI). Ideally, acceleration voltage
would be applied to a population of ions with unique initial velocities
per each m / z value. However, vaporization and ionization distribute
initial kinetic energy on the ions, therefore resulting in different initial
velocities of ions with the same m / z values. Ions with the same m / z
value travel the field-free tube accelerated at different initial velocities
and reach the detector over a time interval (

=

∆ t ). Consequently, ∆ t even-

tually results in m / z , therefore affecting the resolution of mass

measurement. By using longer flight tubes, one could minimize the
effects of initial velocities. An alternative solution is to use a reflectron
(figure 1.1a). A reflectron focuses ions of same m / z but different initial
velocities by reversing their flight path, with lower initial velocities

∆