A robust and efficient software algorithm is presented that automatically optimizes the performance of a single quadrupole mass spectrometer for any user-supplied calibrant in 3 steps: 1) it tunes the extraction electrode and hexapole bias voltages to maximize signal intensity for all masses, 2) it tunes the hexapole RF, ion energy, and resolution voltages to optimize peak quality factors like intensity, resolution, and symmetry for each mass, and 3) it determines ramps for these voltages to provide good performance across all masses.

1. Automated Tuning of a Single Quadrupole MS System
for User-Supplied Calibrants
Overview: Instrument Voltages to be Tuned
Summary:
Introduction:
Ben Trumbore, Simon Prosser, Nigel Sousou
Advion, Inc. 30 Brown Rd, Ithaca, NY 14850
A mass spectrometer tuned to specific
compounds can produce more intense
and accurate signals for those
compounds than when it is tuned
using a generic calibrant mixture. It is
challenging to achieve this benefit
while maintaining efficiency,
robustness and ease of use.
The presented algorithm requires
users to declare the masses of the
compounds that are to be targeted by
the algorithm. It also ensures that the
initial voltages and mass calibration
are such that peaks can be seen at
these masses. The ensuing
auto-tuning process is described
below. After the instrument’s voltages
have been tuned, a mass calibration is
performed to complete the
auto-tuning process.
This algorithm was implemented in
Advion’s Mass Express software for
controlling the Advion expression
Compact Mass Spectrometer (CMS).
The auto-tuning process described here operates only
on voltages that are applied within the instrument’s
chambers. Voltages used to optimize the behavior of
an ion source are not included, allowing multiple ion
source optimizations to be used with a single set of
tuned instrument voltages. Detector gain is also not
auto-tuned.
Compounds Used to
Produce Sample Data
An algorithm is presented that allows a single quadrupole
mass spectrometer to be automatically tuned to any
user-supplied calibrant containing one or more
compounds. Its run-time is proportional to the number of
masses targeted by the user. The algorithm incorporates
different analysis techniques as appropriate for the
voltage(s) being tuned.
A robust and efficient software
algorithm is presented that
automatically optimizes the
performance of a single quadrupole
mass spectrometer for any
user-supplied calibrant.
Auto-tunable Parameters
Extraction Electrode
Hexapole Bias
Hexapole RF Ramp
Ion Energy Ramp
Resolution Ramp
Ion Source Parameters
Ion source voltage
Ion source gas temperature
Capillary voltage
Capillary temperature
Source voltage ramp
Name m/z
Chloride 34.97
Nitrite 46.1
Nitrate 62.1
Bromide 78.92
Sulfate 96.96
Tetra (butyl) ammonium bromide 242.28
Tetra (hexyl) ammonium bromide 354.41
Tetra (octyl) ammonium bromide 466.53
Tetra (decyl) ammonium bromide 578.66
Extraction Electrode & Hexapole Bias
These voltages mainly affect signal
intensity and are inter-dependent:
Extraction Electrode must be ≥ Hexapole
Bias. Using Extraction Electrode of 9.0 V,
find the best Hexapole Bias voltage using
an average response for all masses. Then
find the best Extraction Electrode voltage
using an average response for all masses,
selecting the lowest voltage that raises
intensity to the plateau.
Signal Intensity for Several Masses:
Hexapole RF only affects
signal intensity, is
independent of other
voltages, and behaves very
consistently between
instruments, so we use an
explicit ramp instead of
tuning for each instrument.
The voltage range for good
performance is very tight
for low masses, and the
ramp that fits through that
window is not ideal for
higher masses.
Hexapole RF
Ion Energy & Resolution
These highly inter-dependent voltages
affect peak intensity, resolution and shape,
and poor settings make peaks disappear.
They are tuned by first defining a function
for evaluating peak “quality”, which
multiplies peak intensity by evaluators for
peak resolution and shape. Then, for each
target mass, find a voltage pair that
optimizes this function. Finally, find
parameter ramps that most closely fit the
best voltage pairs for all target masses.
R e s o l u t i o n
function appraises
peak width at half
height such that
0.6 evaluates to 1.0
and below 0.45 or
above 0.75
evaluate to 0.0.
Shape function appraises
peak symmetry about its
centroid by comparing
the peak’s front and tail
partial-widths at half
height, evaluating a
width imbalance of 0 to
be 1, and an imbalance
of 0.2 to be 0.
• Green is desirable, blue and red are not.
• Combining evaluation functions reduces the number of candidate voltage pairs.
Dark green region is best voltage combination for this mass.
expression CMS
Quadrupole AnalyzerHexapole Detector
~2 mbar
~5 x 10-3
mbar ~5 x 10-6
mbar
Heated Capillary Inlet
Electrospray Probe
Compact Mass Spectrometer
ESI Voltage
Hexapole
RFHexapole
Bias
Extraction Electrode
Capillary
Voltage and
Temperature
Source
Voltage
Ion Energy
Pole Bias
(fixed)
Resolution adjusts
RF/DC ratio
Detector
Gain
Dynode
Electron
Heated Desolvation Gas
Nebulization Gas
multiplier
Simultaneous Selection of Resolution and Ion Energy Voltages to
Produce Best Peak Resolution, Symmetry and Intensity
Application of Evaluation Functions for m/z 242.28:
Evaluation Functions:
0.1
0.2
0.3
0.4
0.5
-3.0
-2.6
-2.2
-1.8
-1.4
-1.0
-0.6
-0.2
0.2
0.6
1.0
1.4
1.8
2.2
2.6
3.0
Resolution(volts)
Ion Energy (volts)
Intensity 0E+0-1E+8
1E+8-2E+8
2E+8-3E+8
3E+8-4E+8
4E+8-5E+8
5E+8-6E+8
6E+8-7E+8
7E+8-8E+8
0.1
0.2
0.3
0.4
0.5
-3.0
-2.6
-2.2
-1.8
-1.4
-1.0
-0.6
-0.2
0.2
0.6
1.0
1.4
1.8
2.2
2.6
3.0
Resolution(volts)
Ion Energy (volts)
Peak Shape -0.2--0.15
-0.15--0.1
-0.1--0.05
-0.05-0
0-0.05
0.05-0.1
0.1-0.15
0.15-0.2
0.1
0.2
0.3
0.4
0.5
-3.0
-2.6
-2.2
-1.8
-1.4
-1.0
-0.6
-0.2
0.2
0.6
1.0
1.4
1.8
2.2
2.6
3.0
Resolution(volts)
Ion Energy (volts)
Resolution 0.4-0.45
0.45-0.5
0.5-0.55
0.55-0.6
0.6-0.65
0.65-0.7
0.7-0.75
0.75-0.8
Over-resolved
Under-resolved
Fronting
Tailing
Poor
Intensity
0.1
0.2
0.3
0.4
0.5
-3.0
-2.6
-2.2
-1.8
-1.4
-1.0
-0.6
-0.2
0.2
0.6
1.0
1.4
1.8
2.2
2.6
3.0
Resolution(volts)
Ion Energy (volts)
Intensity, Resolution and Peak Shape 0E+0-1E+8
1E+8-2E+8
2E+8-3E+8
3E+8-4E+8
4E+8-5E+8
0.1
0.2
0.3
0.4
0.5
-3.0
-2.6
-2.2
-1.8
-1.4
-1.0
-0.6
-0.2
0.2
0.6
1.0
1.4
1.8
2.2
2.6
3.0
Resolution(volts)
Ion Energy (volts)
Resolution and Peak Shape 0.0-0.1
0.1-0.2
0.2-0.3
0.3-0.4
0.4-0.5
0.5-0.6
0.6-0.7
0.7-0.8
0.8-0.9