Quadrupole Ion Filters

Quadrupole mass filters are perhaps the most widespread analyzers in mass spectrometry. Quadrupoles are used as a single mass filter or in hybrid combinations like triple-quadrupole (QqQ), Q-TOF (time-of-flight), Q-Exactive (quadrupole combined with Orbitrap), and other instruments for both GC-MS and LC-MS analyses. The triple-quad GC-MS/MS and LC-MS/MS instruments are undisputed leaders for reliable and sensitive targeted analysis.

In our laboratory quadrupole mass filters are installed on several instruments: GC-MS (single-quad, Agilent), GC-QTOF 7200 (in combination with TOF, Agilent), GC-MS/MS triple-quad TSQ 9000 (Thermo Scientific), LC-MS/MS QTRAP 6500+ (Sciex), Q-Exactive Plus (in combination with Orbitrap, Thermo Scientific).

A quadrupole mass analyzer consists of four parallel metal rods to which specific direct current (DC) and radio-frequency (RF) voltages are applied. Segments 180 degrees apart are electrically connected. Segments 90 degrees apart are electrically isolated from each other. Radio frequencies of adjoining segments are 180 degrees out of phase with each other. One connected pair has a positive DC voltage added to the RF voltage, and the other connected pair has a negative DC voltage added to the RF voltage. The pair with a positive bias is the high pass filter that filters out all masses lower than the selected m/z. The pair with a negative bias is the low pass filter that filters out all masses higher than the selected m/z.

A varying RF voltage combined with a DC voltage is applied to the two pairs of segments. The magnitude of the RF voltage determines the m/z of the ions that pass through the mass filter and reach the detector. The ratio of DC-to-RF voltages determines the resolution (widths of the mass peaks). There are two parameters that control the DC and RF voltages, - AMU gain and AMU offset (AMU - the atomic mass unit is equivalent to Dalton).

As the voltages are increased, ions with increasing m/z values are allowed to pass through. A full MS scan is obtained by increasing the opposite polarity but keeping the same magnitude DC voltage with the same RF voltages applied to the connected pairs of hyperbolic surfaces over an expanded range of values.

The diagram of ion stability in the hyperbolic quadrupole field while increasing opposite polarity DC voltage and 180 degree out of phase RF voltage applied to the adjacent hyperbolic surfaces of a quadrupole mass filter is shown in the following figure. This plot is known as a Mathieu Stability Diagram. The shaded area represents a stable region that allows the 152 m/z ion to pass through the quadrupole and be counted by the detector. The region to the left of this stable region filters out all ions with a lower m/z, and the region to the right filters out all ions with a higher m/z value. The stable region also includes overlapping stable regions for other ions allowing them to also pass through the quadrupole. To obtain unit resolution on the 152 m/z ion the quadrupole must be adjusted so that only ions with an m/z of 151.5 to 152.5 can reach the detector.

The next figure is an example of a Mathieu Stability Diagram showing how the detection of 3 ions varies with the DC and RF voltages on opposing poles of the mass filter. Each DC/RF pair that allows a certain mass/charge to oscillate with stability through the quadrupole is indicated by a separate curve. The goal is to obtain a unit mass resolution and a half-height peak width of 0.5 AMU by varying the AMU Gain and AMU Offset. The slope of the Scan line is the AMU Gain. Its Y-axis intercept is the AMU Offset. The region above the Scan line has a unit resolution for these three ions. Increasing the lines offset improves specificity at the cost of resolution and peak width.

The slope of the scan line is the AMU Gain. Adjusting the AMU Gain affects the ratio of DC voltage to RF frequency on the mass filter, which controls the mass of the ions filtered by the mass analyzer and the width of the mass peaks. A higher gain gives narrower peaks. Changing this parameter has a greater effect on the high mass peaks than on the low mass peaks. Similar to AMU Gain, AMU Offset can also control the widths of the mass peaks. A higher offset also yields narrower peaks equally at all masses.

When the quadrupole is operated in RF-only mode without DC voltages applied, all ions of m/z higher than defined by a low mass cutoff will (theoretically) pass the quadrupole analyzer. 

Low m/z cutoff. By selecting an appropriate RF frequency and potential, the quadrupole acts like a high pass filter, transmitting high m/z ions and rejecting low m/z ions. The low m/z ions have a greater acceleration rate so the wave for these ions has a greater amplitude. If this amplitude is great enough the ions will collide with the electrodes and can not reach the detector. The low m/z value cutoff of the quadrupole is changed by adjusting the RF potential or the RF frequency. Any ions with m/z greater than this cutoff are transmitted by the quadrupole.