The Advantages and Disadvantages of Specific Mass Spectrometry Platforms

What are the Pros and Cons and Performance Metrics of Different Mass Spectrometry Platforms?

It’s well acknowledged that each mass analyzer (and ionization source) has unique performance attributes and limitations. The type of configuration, whether it is an ESI-quadrupole or a MALDI-TOF for example, is largely dictated by the flavor of research and the molecules of interest – and sometimes by the instrument or resources available. Regardless, it is important to know the capabilities of each instrument to determine whether it is right (or at least adaptable) for your research needs. If not, it’s probably time to upgrade components or instruments.

Quadrupole mass analyzer

A quadrupole (or quad) is a type of mass analyzer which consists of four cylindrical rods set in parallel arrangement, which functions as a mass filter for ions entering from the ionization source. Expressed as their mass to change ratio, ions are separated based on the stability of their flight paths when oscillating electric fields are applied to the quadrupole.

Quadrupole mass spectrometer pros

  • Typical mass range – 3000 mass to charge (m/z)
  • Typical resolution – 2000 – the observed m/z divided by the Δm/z for two ions that can be separated
  • Tolerance for high pressure – atmospheric
  • Well-suited for electrospray
  • Ease of switching between positive and negative ions
  • Small size
  • Relatively low cost

Quadrupole mass spectrometer cons

  • Mass range limited to about 3000 m/z
  • Poor adaptability to MALDI

Triple Quadrupole mass analyzer

A triple quad consists of three quadrupoles in series (Q1, Q2, and Q3). Q2 and Q3 acts as mass filters while the central Q2 functions as a collision cell. The Q2 cell is subjected to an inert collision gas such as Ar, He, or N2, in a process known as colission induced dissociation (CID). Daughter fragments of the Q1 selected parent ions are subsequently filtered or scanned by Q3.

Triple Quadrupole mass spectrometer pros

  • MS/MS capabilities for small molecule, peptide, or protein analysis
  • Fast scan speeds and ability to measure positive and negative ions simultaneously (with approprite ionization source).
  • Ability to analyze many (up to several hundred) single reaction monitoring (SRM) or multiple reaction monitoring (MRM) events in a single run.
  • Can interface with multiple electrospray ionization including atmospheric pressure sources.
  • Off-axis detectors, curved collission cells, and a multitude of advanced component technologies make the platform highly desirable from size, throughput, and versatility standpoints.
  • Ability to interface with several mass analyzers in hybrid configurations.

Triple Quadrupole mass spectrometer cons

  • Although compatible with multiple high pressure electrospray sources, not compatible with MALDI ionization.
  • Samples must undergo preparation according to electrospray procedures, thus complex matrices such as blood, tissues, and cell lysates require fractionation, abundant protein depletion, and other procedures to unmask desired analytes.

Ion Trap mass analyzer

An ion trap mass analyzer uses a combination of electric and magnetic fields (DC and radio frequency) to capture and suspend ions prior to selection and detection.

  • A quadrupole trap (or Paul trap) uses static CD and RF oscillating electric fields, two metal electrodes with foci facing each other, and a ring electrode in between, to effectively trap ions in the center region.
  • The modified Kingdon trap or Orbitrap includes a cylindrical electrode and isolated end cap electrodes, along with a static applied voltage, to store ions in a angular orbit around a central wire.
  • A Penning trap stores charged ions using a strong homogenous axial magnetic field to stabilize the molecules radially, and a quadrupole to stabilize ions axially. This type forms the basis for Four Transform Ion Cyclotron Resonance mass spectrometry.

Ion Trap mass spectrometry pros

  • Range 2000 m/z
  • Resolution 1500
  • Small size
  • Medium resolution
  • Simple design – Low cost
  • Well suited for tandem MS
  • Easy for positive/negative ions

Ion Trap mass spectrometry cons

  • Limited mass range – not as much a problem with current innovations

Orbitrap mass spectrometer pros

  • Capability for coupling with linear ion trap (LTQ) or a direct ion source.
  • Compatibility with atmospheric pressure sources such as electrospray and intermediate pressure sources including MALDI
  • High mass accuracy (2 ppm external calibrant, 1 ppm internal calibrant)
  • High resolution (up to 100,000 at m/z 400)
  • High dynamic range and sensitivity

Take a closer look at the Orbitrap

Fourier Transform mass spectrometry (FTICR-MS) pros

  • Since all ions are detected simultaneously (rather than at different places (ion trap) or different times (TOF)), there is a pronounced increase in signal-to-noise ratio over other MS platforms.
  • FTICR resolution can be enhanced by increasing the strength of the magnet or by increasing the duration of detection.
  • Higher levels of mass accuracy are possible over other MS methods due in part to the superconducting magnet, which is much more stable than radio-frequency voltages.
  • The significantly increased sensitivity, accuracy, and resolution enable analysis of complex mixtures or analytes, in which two ion signals with similar m/z ratios can be effectively resolved and detected.
  • Range m/z ∞
  • Resolution 30,000
  • High resolution
  • Well-suited for tandem MS


  • High vacuum required
  • Super conducting magnet required – expensive
  • Extensive maintenance
  • Massive size

Time-of-Flight mass analyzer

TOF is a MS technique in which an ion's m/z ratio is determined by a time-of-flight measurement. Ions are accelerated by an electric field of defined strength resulting in ions of the same charge possessing the same kinetic energy. The velocity of the ion depends on the m/z ratio. The time it subsequently takes to travel down the drift tube and reach the detector can be measured and the ion thus resolved.

Time-of-Flight (TOF) mass spectrometer pros

  • Range m/z ∞
  • Resolution 350
  • Highest mass range
  • Very fast scan speed
  • Simple design – Low cost
  • Ease of adaption to MALDI

TOF mass spectrometer cons

  • Low resolution
  • Difficulty of adaption to electrospray

Time-of-Flight reflectron mass analyzer

The reflectron is an enhancement to a TOF analyzer by which the kinetic energy distribution of ion flight can be corrected. A constant electrostatic field is used to reflect the ion beam back to the detector and, along with better ion focus, this arrangement enables a flight path approximately twice that achieved using a typical TOF.

TOF Reflectron mass spectrometer pros

  • Range m/z ∞
  • Resolution 1500
  • Improved resolution relative to TOF
  • Very fast scan speed
  • Simple design – Low cost

TOF Reflectron mass spectrometer cons

  • Resolving power has limited m/z range
  • Lower sensitivity compared to TOF

Beyond these platforms there is a range of modified or hybrid instrument platforms that allow the pros of multiple techniques to be harnessed for extended applications. For example:

Quadrupole Time-of-Flight (QTOF) mass spectrometer pros

  • Interface with electrospray and atmospheric ionization sources.
  • Capabilities for tandem (MS/MS) analysis.
  • Increased range owing to TOF reflectron.
  • Relatively simple setup and size efficiency.
    Take a look at a diagram of the QTOF.

As you can see, the differences between these instrument platforms is significant in terms of capabilities, limitations, adaptability, requirements, and size. Each type has a specific set of skills that allow it to excel in given applications. Moreover, there are many modifications and emerging improvements in performance which make the capabilities of the described platforms an evolving science. A good example of this is the range of Orbitrap platforms and applications.

An important point is that limitations of performance and functionality may not significantly impact your analysis, depending on the demands of your application. Other applications may demand increasing accuracy and resolution for complex analysis.

View the mass spectrometry resource library for more information and technical insight.