June 14, 2024
by Baljit Bains, Marketing Communications Specialist, ACD/Labs
In the Beginner’s Guide to Mass Spectrometry blog series, you will have learned about the steps involved in MS—ionization, ion separation by a mass analyzer, detection, deflection, and data processing.
Central to this process are the components that separate ions based on their mass-to-charge ratio—mass analyzers. The choice of mass analyzer can have a significant impact on the resolution, accuracy, and speed of the analysis; making it crucial for scientists to understand the various types available and their respective advantages.
In this final installment, we will delve into the different types of mass analyzers in mass spectrometry including time-of-flight (TOF), quadrupole, ion trap, and Fourier transform analyzers. Understanding their unique features and applications can help select the most appropriate mass analyzer for the specific needs of your analysis. With the possibility of combining mass analyzers to create tandem or hybrid mass spectrometers, scientists can improve experimental results and achieve higher throughput experiments.
Acceleration
In the mass analyzer, ions are accelerated through a potential difference and focused into a beam. The purpose of this is to give all the molecules the same kinetic energy. The ions are between a set of charged parallel plates where they are attracted to one and repelled from the other. Adjusting the charge on the plates controls the acceleration speed.
Types of Mass Analyzers
There are several mass analyzers available, and each has their own place within different experiments and applications.
Time-of-flight (TOF)
A time-of-flight (TOF) mass analyzer is unique in that it does not require an electric or magnetic field. It works by separating ions based on their flight times over known distances. It measures the time taken for an ion to travel a specific distance with a specific kinetic energy, to determine the m/z ratio. Separation is based on the velocity and kinetic energy of ions. Ions with a smaller m/z ratio travel faster than those with a larger m/z ratio. Typically, TOF is quite sensitive and has quick scan speeds.
Magnetic Sector
Magnetic sector mass analyzers are like TOF mass analyzers, with the key difference being that a magnetic field is used to separate the ions. In magnetic sector mass analyzers, high voltage is applied to the ions to accelerate them through a flight tube in the magnetic sector, where the ions will separate based on m/z ratios. Ions with selected m/z values will deflect similarly and travel on the same trajectory to the detector. Ions not selected will collide with the tube walls and not pass through to the detector.
Magnetic sector analyzers have high resolution but have slower scan speeds than most other mass analyzers.
Quadrupole
Quadrupole mass analyzers are the most common type of mass analyzers used due to their quick scan speeds, sensitivity, and ease of use. A quadrupole mass analyzer is a low-resolution analyzer that is ideal to use with LC/MS and GC/MS. Quadrupole analyzers are made up of 4 parallel rods. Each opposing pair of rods is connected electrically, and a radio frequency (RF) is applied between them. Ions of a certain m/z ratio will reach the detector for a given ratio of voltages. Varying the voltage applied allows targeting of ions either with a specific m/z ratio or within a set range of m/z ratios to transmit through the analyzer. Ions separate based on the stability of their paths in the oscillating electric fields applied to the rods.
Ion Trap
Ion trap mass analyzers use a combination of electric or magnetic fields to “trap” ions within the analyzer. Ion trap mass analyzers work by using the electric/magnetic field in the cavity to get ions of specified m/z values to orbit in the cavity. Specific ions can be excited by energy from the electrode and ejected to the detector. This is useful, as ions with m/z not of interest can be ejected and further fragmentation on the ions of interest can be performed. Gradually increasing the applied RF voltage allows for the selective ejection of ions from the “trap” in order of increasing m/z ratio. As ions leave, they strike a detector and create an output signal.
There are two types of ion trap mass analyzers: 2D and 3D.
3D ion traps work similarly to quadrupole mass analyzers, but with different configurations. In a 3D ion trap mass analyzer, two hyperbolic metal electrodes (end caps) are facing each other, and a ring electrode is placed halfway between these. Ions become trapped between the electrodes due to the applied oscillating RF potential and static DC current. Selective ejection and detection of ions with specific m/z ratios occur by applying varying RF potential.
2D ion trap (also called a linear trap) uses quadrupole rods with electrodes on each end to facilitate ion trapping. This allows it to be used as either a quadrupole mass filter or as an ion trap. The selected ions are ejected either radially or axially.
Ion trap mass analyzers are widely used in mass spectrometry for protein and metabolite identification, and screening applications.
Orbitrap
The orbitrap mass analyzer is made up of a central spindle-like electrode surrounded by an outer barrel-shaped electrode. The outer electrode is split laterally into two halves. Electrostatic voltages are applied to either the inner or outer electrodes or applied to both sets of electrodes, creating an electric field. This causes ions injected into the space between the inner and outer electrodes to undergo orbital motion around the central electrode. The frequency of the motion is characteristic of the ions’ m/z. The analyzer measures the frequency of ions injected simultaneously into an electrostatic trap, creating a back-and-forth motion.
Orbitrap mass analyzers are high-resolution and have a wide range of applications, including the identification of unknowns in biomarker discovery, metabolism, clinical research, forensics, and food safety.
Fourier Transform Mass Spectrometry (FTMS)
FTMS combines ion trap and Fourier transform ion cyclotron resonance (FTICR) in a single instrument. The FTMS mass analyzer determines the m/z ratio of ions based on their cyclotron frequencies in a fixed magnetic field. The ions are trapped in the magnetic field between the electric plates where an oscillating electric field applied perpendicularly excites them to a larger cyclotron radius. As the excitation field is removed, the ions rotate at their cyclotron frequency as a “packet” of ions. As this packet of ions passes close to the electrodes, it induces a charge resulting in a free induction decay signal. Applying the Fourier transform mathematical operation on this signal generates a mass spectrum.
Mass resolution is dependent on magnetic field strength and time of observation (scan time). FTMS is a very sensitive technique providing excellent accuracy (up to units of parts per billion) and ultra-high resolution. It can be used to identify structures, allowing access to ion elemental formulas. However, the operation and maintenance of FTMS machinery can be costly, difficult, and slow.
Tandem Mass Spectrometry (Tandem MS)
Tandem mass spectrometers (MS/MS) combine mass analyzers in sequence. In the first analyzer (MS1), the formed ions of a defined m/z ratio pass through. These are then split into ion fragments in the collision cell and analyzed by the second analyzer (MS2). Tandem MS is an automated technique that is useful in large-scale analysis as it allows users to conduct multiple rounds of mass spectrometry experiments.
Added benefits of tandem MS include the ability to study numerous molecules (regardless of whether they are from the same structural family) and the capacity to highlight specific metabolites of a disease.
Hybrid Mass Analyzer
It is possible to combine various mass analyzers into one mass spectrometer to perform advanced experiments with more specific separation, resolution, and detection requirements. Hybrid mass spectrometers are a type of tandem MS that combines two (or more) different mass analyzers, increasing versatility and providing higher analytical performance. Examples of hybrid mass spectrometers include:
- Sector Quadrupole
- Q-TOF: Quadrupole + Time of Flight
- Q-Trap: Quadrupole + Ion Trap
- Ion Trap Time of Flight
- Linear Ion Trap + Fourier Transform Mass Analyzers
Understanding the capabilities and limitations of each type of mass analyzer allows scientists to make informed decisions—optimizing their mass spectrometry workflows for better accuracy, efficiency, and overall performance.
Through this blog series, we have covered the basics of mass spectrometry. Understanding the basic principles including ionization methods, mass analyzers, and detectors is key to setting the stage for the analysis and characterization of molecules.
Learn more about ACD/Labs Mass Spectrometry software here.
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