Mass Analyzers

After the production of ions in ion sources, the next critical step in mass spectrometry is to separate these gas phase ions according to their mass-to-charge ratio (m/z). Ions are extracted from the ion source and sent to a device called the Mass Analyzer (Figure 1a). Gas phase ions in motion can be characterized by their momentum, kinetic energy, velocity, and response to electric or magnetic field. Mass analyzers make use of one or more of these properties to distinguish between ions. There are many types of mass analyzers and they can be classified in a variety of ways. One classification (based on their general principle of operation) sorts them into two groups:

Mass filters are devices in which only ions of interest make it through the mass analyzer to the detector (Figure 1b). All other ions are neutralized. Conditions on the mass analyzer are then reset so that other ions are guided to the detector.

Beam analyzers are devices in which the ions are separated according to their m/z such that each ion travels through the mass analyzer and arrives at the detector at q different time or different location on q focal plane (Figure 1c).

Principles of the three most common types – magnetic sector, quadrupole and time of flight - will be discussed herein.

Figure 1a: Ions produced in the ion source (blue and red dots) are extracted (from cloud of neutral compounds and ions) and accelerated by the ion optics into the mass analyzer.

Figure 1b: General principle of operation of a mass filter. With mass filters a mixture of ions that are continuously extracted by the ion optics are introduced into the mass analyzer. Under a set of conditions imposed on the mass analyzer, only one group of ions (with a unique m/z) makes it through to the detector (the red ones in the diagram). Other ions are neutralized and removed from the mass analyzer (the blue ions produced in the ion course in Figure 1a).

Figure 1c: General principle of operation of beam analyzers. In an ideal situation, all m/z ions successfully make it through the mass analyzer, but they arrive at the detector at different times or at different points in space (i.e. the ions are spatially resolved). In the diagram, the blue and red ions will make it to the detector at different times.

1. Magnetic Sector Mass Analyzers

M a gne t

Ion fligh t tube

Ion

S ou rce IonD e te c to r

Ion

Ex trac tion

op tic s

Figure 2: Schematic diagram of a magnetic sector instrument.

These are first generation mass analyzers that date back to the days of J.J. Thompson experiment on analysis of positive rays. As the name indicates, they are comprised of a magnet that typically is in a semi-circular shape. An ion flight tube runs through the magnet (see Figure 2). The interaction of ions with the magnetic field can be modeled by the following expression:

Where m is the mass of the ion (in kg), z is the number of charges on the ion, e is the electronic charge (1.602 x 10-19C), r is the radius of the ion path through the flight tube, V is the acceleration potential of the ions and B is the strength of the magnetic field (in Tesla, T).

From this expression, it can be predicted that at a given value of B and V, ions with smaller m/z will travel in a path of smaller radius compared to an ions with a bigger m/z ratio. However, only ions that travel in a path that is similar in radius to the flight tube can successfully make it through to the detector. Other ions travel in a path that leads them to collide with the wall of the flight tube. They become neutralized and are pumped out of the tube under the prevailing low pressure (~10-6 Torr) condition. Varying the magnetic field while keeping the acceleration potential (V) constant will vary which ions (of select m/z) successfully make it through the flight tube to the detector. Monitoring the signal that is generated by the detector for each group of ions and plotting that signal versus the m/z of each group results in the mass spectrum

2. Quadrupole Mass Analyzers

Figure 3: Schematic diagram of a quadrupole mass analyzer.

The quadruple mass analyzer is also called a mass filter (Figure 3). It consists of four rods (conducting metals). Separation of gas phase ions is achieved by creating an electric field that makes the ions oscillate within the space between the rods. At a particular set of conditions, only one m/z ion has the correct oscillation to make it through the quadrupole to the ion detector. Other ions oscillate with so much amplitude that they collide with one of the rods and are neutralized and pumped out of the system. To accomplish the oscillation, a positive dc voltage is applied to one pair of the rods and a negative dc potential is applied to the other pair. Additionally, an alternating radiofrequency voltage is superimposed on the rods. At an instant of time, the ions are attracted to one pair of the rods and repelled by the other pair.

Figure 4: Representation of the pair of rods on the y-z plane of a quadrupole mass analyzer.

Assuming that the ions are positively charged, when they oscillate in the y-z plane (that is they are vibrating in the y direction while travelling in the z direction), they experience repulsion from the positively charged rod (Figure 4). This repulsion focuses them onto the z-axis. This is strongly the case during the positive cycle of the superimposed rf potential. However, during the negative cycle of the rf potential, the ions are slightly defocused away from the z-axis. Relatively high m/z ions are less affected by this defocussing. Relatively low m/z ions are more affected and can oscillate high enough that they collide with the rods. Upon collision with the rods, they are neutralized and are removed from the analyzer chamber (i.e. they are filtered out). With a certain combination of dc (U) and ac (Vsin t) potentials, a group of ions with similar m/z will successfully travel through the analyzer to the detector. When the dc-ac conditions are changed, another group of ions of another m/z will successfully navigate their way to the detector. Repeating this process such that a range of ions (i.e. a range of m/z) are eventually guided to the detector sequentially is called scanning. Two dimensionless parameters, a and q (shown below) define the conditions for successful oscillation.

, Re-arranging we get:

and

Where ro is the inscribed radius (or ½ the distance between opposite pair of rods, in ‘m’) = 2f, and ‘f’ is the radio frequency m is the mass of a single ion in kg e is electronic charge (1.602 x 10-19C), U is the dc potential (in V) V is the rf potential (in V)

During scanning, U and V are varied linearly to keep their ratio constant ( a/q = 2U/V ). At a particular combination of U and V, values of a and q are set and this determines which m/z ion navigates successfully though to the detector.

3. Time-of-flight Mass Analyzer

In a time-of-flight (TOF) mass analyzer, ions from the ion source are directed into a region where they are repelled and accelerated into a field-free flight tube. The repulsion and acceleration of an ion depends on its m/z ratio. Therefore, ions in the flight tube travel at different speeds and arrive at the detector at different times (Figure 5).

Figure 5: Schematic diagram of a time-of-flight mass analyzer.

The time of arrival of an ion is given by the expression:

Or

Where t is the time, v is the velocity, and L is the distance (in m) between the extraction optics and the detector. L can be approximated with the length of the flight tube. Note that ions with smaller m/z will travel faster and reach the detector sooner.

A TOF mass analyzer is calibrated with compounds of known molecular weight and fragments so that the time can be related to several m/z values.A generally accepted calibration equation is:

A TOF mass analyzer is an example of a beam analyzer because all the ions in a packet are transmitted to the detector.

4. Ion Trap Mass Analyzers

Ion traps are mass analyzers that can perform dual roles of ion storage and mass analysis. A few things to note about ion traps are that:

The ions are typically stored for only a limited period of time, There is a limit to the amount of ions that can be stored in a given device otherwise

development of space charge may lead to resolution problems. Ion traps can also function as molecule-fragmentation and mass a selective device

There are several kinds of ion traps which can be broadly classified as indicated in Figure 1 below:

Figure 1: A Classification of ion trap devices. Note: LIT means linear ion trap. QIT means Quadrupole ion trap

The 3D QIT will be discussed here as an example (representative) of ion traps. Three-dimensional quadrupole ion traps (3D, QITs’) are commonly employed in the GC-MS systems that are frequently found in undergraduate laboratories. These devices confer multiple stage mass spectrometric (MSn) capability, small size and low cost nature to the bench-top GC-MS systems.

Figure 2: Schematic diagram showing the electrodes of a quadrupole ion trap (QIT).

Three-dimensional QIT’s comprise of three electrodes: two end-caps and a ring electrode (see Figure 2). Both end cap electrodes have orifices for ion injection and ejection. An ion source is placed in front of the entrance end-cap electrode and a transducer is positioned behind the exit end-cap electrode. Operation of the QIT can be broken into following steps: ion injection, ion trapping, ion fragmentation (if necessary), and sequential ion ejection and detection (i.e. mass analysis). Each of the steps is further described below:

Ion InjectionElectron and chemical ionization devices are used for generating ions from thermally stable and volatile molecules, while electrospray ionization device is used to generate ions from polar and non-volatile molecules. These externally generated ions are extracted with appropriate lenses into the trap. The amount of ions injected/extracted into the trap is controlled to avoid space charge which can subsequently disrupt mass resolution. Ions are injected into the trap in batches. The ions are trapped, fragmented (if necessary), analyzed and detected before the next batch of ions is introduced trapping chamber.

Ion TrappingSince the kinetic energies of externally generated ions are typically too high to permit efficient trapping, a bath gas (e.g. helium) is allowed into the chamber to cause their collisional cooling (i.e. the reduction of their kinetic energy). This cooling also enables the confining of ions to (or near) the center of the trapping chamber. This is important because ions that travel closer to the electrodes are easily lost due to the steeper gradient of the electric field near the chamber. To sustain the ions in stable trajectories within the chamber, a high ac voltage called the ‘fundamental RF’ is applied to the ring electrode while the end caps are kept grounded. This

makes each ion to oscillate axially while travelling in a circular trajectory which is similar to the Lissajous shape. Frequency of oscillation of the ions under this condition is called the ‘secular frequency’. Ions of same m/z have a unique secular frequency of oscillation.

Ion FragmentationTo facilitate fragmentation of the trapped ions, a small auxiliary RF voltage is applied to the end-caps. When the frequency of this auxiliary voltage matches the secular frequency of an ion, the amplitude of its axial oscillation is increased and it collides with the bath gas and fragments. Such an ion is described as tickled and the voltage that is used in effecting the excitation is called the ‘tickle voltage’. Magnitude of the tickle voltage (or auxiliary voltage) is about 100mV.

Ion Ejection/Mass AnalysisA few methods are utilized for ion ejection from the trap but only the resonance ejection approach will be described here for simplicity. To initiate resonance ejection of ions with a particular m/z, first the corresponding fundamental RF is set, and the amplitude (magnitude) of the auxiliary RF is increased until its frequency matches the secular frequency of the desired ion (i.e. m/z). The trajectory of these ions is destabilized, as their axial oscillation increases and they escape through the orifice of the exit end cap to the detector. The fundamental and auxiliary rf voltages are then changed the next ion is then ejected.

Advantages of ITMSa. ITMS generally have high sensitivity. This is facilitated by their ion storage/accumulation

ability, coupled with the fact that ions that are not of interest can be rejected. Combination of these two factors leads to high signal –to-noise ratio and consequently high sensitivities.

b. ITMS can be used for Multistage mass spectrometry (MSn) studies in which parent/precursor ion can be fragmented, and the fragment can be further fragmented to obtain structural information of molecules.

c. QIT in particular can be coupled with ions sources that are operated at modest (e.g. CI) to high pressures (ESI).

d. The small size of these mass analyzers enables the design of bench-top mass spectrometers (e.g. GC-MS).

Disadvantagesa. ITMS are not generally good for quantitationb. They have limited dynamic rangec. Collision energies are not well defined when operated in the collision induced

dissociation (fragmentation) mode, thereby leading to irreproducibility of ions.d. There are too many parameters to control to obtain quality mass spectrum

Describing Performance of Mass Analyzers

Several important parameters describe the performances of a mass analyzer

The mass range is the highest m/z that can be analyzed on a particular mass analyzer.

Resolution is a measure of the mass analyzer’s ability to separate and distinguish ions of similar masses. Mathematically, it is calculated using the expression:

Where m2 is the larger of the two masses and m is their difference.

Mass Accuracy is defined as the error in measuring the mass in m/z of a particular ion divided by its calculated exact mass.

Mass Error = Exact Mass – Measured mass(Note: measured mass is the experimentally measured mass while Exact Mass is the calculated mass based on the sum of exact masses of each atom in the molecule). Tables of exact masses of atoms are commonly available (e.g. http://www.nist.gov/pml/data/comp.cfm )