How a Mass Spectrometer Works

The mass spectrometer is one of the most versatile instruments available to the analytical chemist. It can analyze samples that are gases, liquids, or solids. It is used to analyze individual atoms or complex biopolymers. When coupled with chromatography, which is a broad range of methods used to separate mixtures, it can characterize rather complicated substances. It has applications in fields ranging from environmental monitoring to medical testing. Mass spectrometers have even been used in space exploration. This versatility is possible because of decades of research that has gone into adapting the mass spectrometer to various types of analysis. The driving force behind this research is the fact that the mass spectrometer is essentially a very sensitive balance that works at the molecular scale. Since chemical analysis is basically determining at the atomic and molecular scale what a sample is made of and in what proportion, a ‘molecular balance’ is a powerful tool indeed.

But how does a mass spectrometer work? Mass spectrometers must be able to do three things:

– convert a portion of the sample into particles with electrical charge (ions)
– separate the resulting ions by mass
– detect the ions

Ionization of the sample is essential for the operation of the mass spectrometer since the instrument relies on electric and magnetic fields to ‘weigh’ the molecules that compose the sample. Many ionization techniques have been developed over the years. One of the earliest techniques, electron impact ionization, involved bombarding the sample with electrons. Some of the electrons strike sample molecules in such a way that the sample molecule loses an electron and becomes positively charged. In another method, chemical ionization, the sample is ionized via chemical reactions. A gas, such as methane, is bombarded with electrons to form very reactive molecular ions. These molecular ions then react with the sample molecules, which become ionized themselves.

Both electron impact and chemical ionization require the sample to be in the gas phase. Techniques that allow for the analysis of non-volatile liquids or even solids often rely on a process called desorption. In desorption, energy is applied to the surface of the sample. This causes the molecules to detach from the surface as gaseous ions. One example, called MALDI (Matrix-Assisted Laser Desorption Ionization), is used in the analysis biomolecules. The sample is first mixed with another substance called the matrix. Desorption is accomplished by firing a laser at the mixture. The purpose of the matrix is to help transfer energy from the laser beam to the sample molecules. The matrix also helps to absorb excess energy from the laser that would otherwise destroy the sample molecule.

Once it has been ionized, the sample proceeds to the heart of the mass spectrometer, the mass analyzer, where the various ions generated by the sample are ‘weighed.’ By using various combinations of electric and magnetic fields, the ions are separated by mass. (Technically the ions actually are separated by mass-to-charge ratio, but to simplify the discussion we will assume all of the ions have the same charge.) Three common types of mass analyzers are sector, time-of-flight, and quadrupole.

In a sector mass analyzer, the ions pass through an electric field, which causes them to accelerate. The amount of acceleration is dependent on the mass of the ion. Ions with more mass accelerate less than those with less mass. The ions then proceed through a magnetic field. When a charged particle enter a magnetic field, it is deflected from its original course. The amount of deflection depends on the particle’s speed. Faster particles (i.e. the lighter particles that underwent more acceleration when they passed through the electric field) are deflected less and slower particles are deflected more. Most of the particles are deflected away from the detector, but if the speed of the particle is just right, the particle will enter the detector. Therefore, by varying the strength of the magnetic field, one can determine the mass of the ions generated by the sample.

Like the sector analyzer, the time-of-flight analyzer also uses an electric field to accelerate the ions. However, instead of selecting ions by mass with a magnetic field, the analyzer allows the ions to drift before they enter the detector. Since the lighter particles are traveling faster, they will reach the detector first. Therefore, by accurately measuring the time between ionization and detection, the mass of the ion can be calculated.

In a quadrupole analyzer, the ions travel along the intersection of two oscillating electric fields positioned perpendicular to each other and to the path of the ion. As the ion travels toward the detector, it is constantly being deflected vertically and horizontally. If the ion is of the appropriate mass, it will reach the detector. Otherwise, it collides with one of the four electrodes used to generate the electric fields. By varying the strength of the two electric fields, a wide range of masses can be detected.

After exiting the mass analyzer, the ions must then be detected. Usually a device called an electron multiplier is used. After entering the electron multiplier, the strike a surface called a dynode, which is made of a material that ejects electrons when struck by an energetic charged particle. The dynode is oriented in such a way that the ejected electrons end up striking other dynodes. The process causes a cascade of electrons that becomes an electrical signal that is directed to the data acquisition system.

Mass spectrometry is a field nearly a century old. Many more variations on ionization, mass analysis, and detection exist, and the interpretation of the resulting data can involve more effort than the experiment itself. Yet, despite all the complexity, every mass spectrometry experiment consists of those three steps.