The design was complex. The time interval between different compounds flowing out of the chromatograph was hard to control. So, the mass spectrometer had to finish working on one compound before the next one flowed out of the chromatograph. In the early models, the measurements from the mass spectrometer was recorded on graph paper. Highly-trained chemists studied the patterns of peaks to identify each compound. By the 1970s, analog-to-digital converters were added to mass spectrometers. This allowed computers to store and to interpret the results. As computers grew faster and smaller, GC-MS became faster and spread from laboratories into every day life. Today, computerized GC-MS instruments are widely used in environmental monitoring of water, air, and soil. It is also used in the regulation of agriculture, food safety and in the discovery and production of medicine.
The development of small computers has helped in the simplification of GC-MS machines. It also greatly reduced the amount of time it takes to analyze a sample. Electronic Associates, Inc. (EAI) was a leading U.S. supplier of analog computers. In 1964, EAI began development of a computer-controlled mass spectrometer under the direction of Robert E. Finnigan. By 1966, over 500 gas-analyzer instruments were sold. In 1967, the Finnigan Instrument Corporation (FIC) was formed. In early 1968, delivered the first prototype quadrapole GC-MS instruments to Stanford and Purdue University. FIC was eventually renamed Finnigan Corporation and went on to establish itself as the worldwide leader in GC-MS systems.
GC-MS can find all of the compounds mixed together in a sample object. The operator dissolves the sample in a liquid. The operator then injects the liquid into a stream of gas. (Helium, Hydrogen or Nitrogen gas are used most often.) The gas flows through a tube with a special coating. Because each compound in the sample sticks to the coating in a different way, each compound comes out of the tube at a different time. So the coating is used to separate each compound that was mixed together in the sample. As each compound comes out at the end of the tube, it is ionized and gets an electric charge. Most compounds break apart when they are ionized. The different pieces fly under a magnet which separates the pieces based on their weight and charge. A computer then measures all of the pieces of each compound. By comparing the measurements against a computer library of known compounds, the computer makes a list of the names of all of the compounds in the sample. The computer can also tell how much of each compound was in the sample.
The GC-MS is made up of two major building blocks: the gas chromatograph and the mass spectrometer. The gas chromatograph uses a capillary column which depends on the column's dimensions (length, diameter, film thickness) as well as the phase properties (e.g. 5% phenyl polysiloxane). The difference in the chemical properties between different molecules in a mixture will separate the molecules as the sample travels the length of the column. The molecules take different amounts of time (called the retention time) to come out of (elute from) the gas chromatograph. This allows the mass spectrometer downstream to capture, ionize, accelerate, deflect, and detect the ionized molecules separately. The mass spectrometer does this by breaking each molecule into ionized fragments and detecting these fragments using their mass to charge ratio.
These two machines, used together, allow a much finer precision of substance identification than either unit used separately. It is not possible to make an accurate identification of a particular molecule by gas chromatography or mass spectrometry alone. The mass spectrometry process normally requires a very pure sample. In the past, gas chromatography use other detectors such as a Flame Ionization Detector. These detectors cannot separate different molecules that happen to take the same amount of time to travel through the column. (When two different molecules have the same retention time they are said to "co-elute".) The co-eluting molecules will confuse the computer programs that are reading a single mass spectrum for both molecules.
Sometimes two different molecules can also have a similar pattern of ionized fragments in a mass spectrometer (mass spectrum). Combining the two processes reduces the possibility of error. It is extremely unlikely that two different molecules will behave in the same way in both a gas chromatograph and a mass spectrometer. Therefore, if a mass spectrum matches the analyte of interest, the retention time of that spectrum can be checked against a characteristic GC retention time to increased confidence that the analyte is in the sample.
The most common type of MS associated with a GC is the quadrupole mass spectrometer. Hewlett-Packard (now Agilent) markets it under trade name "Mass Selective Detector" (MSD). Another relatively common detector is the ion trap mass spectrometer. Additionally one may find a magnetic sector mass spectrometer. However these particular instruments are expensive and bulky and not typically found in high-throughput service laboratories. Other detectors are used such as time of flight (TOF), tandem quadrupoles (MS-MS) (see below), or in the case of an ion trap MS. The n indicates the number mass spectrometry stages.
A mass spectrometer is typically used in one of two ways: Full Scan or Selective Ion Monitoring (SIM). The typical GC-MS can work either way alone, or both at the same time.
When collecting data in the full scan mode, a target range of mass fragments is selected and put into the instrument's method. An example of a typical broad range of mass fragments to monitor would be "m/z" 50 to "m/z" 400. The determination of what range to use is largely set by what one expects being in the sample while being aware of the solvent and other possible interferences. If an MS looks for mass fragments with a very low m/z, it may detect air or other possible interferring factors. Using a large scan range decreases the sensitivity of the instrument. The machine will perform fewer scans per second because each scan will take more time to detect a wider range of mass fragments.
Full scan is useful in determining unknown compounds in a sample. It provides more information than SIM when it comes to confirming or resolving compounds in a sample. Most instruments are controlled by a computer which operates a computer program called an "instrument method." The instrument method controls the temperature in the GC, the MS scan rate and the range of fragment sizes being detected. When a chemist is developing an instrument method, the chemist sends test solutions through the GS-MS in full scan mode. This checks the GC retention time and the mass fragment fingerprint before moving to a SIM instrument method. Specialized GC-MS instruments, such as explosive detectors, have an instrument method pre-loaded at the factory.
In selected ion monitoring (SIM), the instrument method focuses on certain ion fragments. Only those mass fragments are detected by the mass spectrometer. The advantages of SIM are that the detection limit is lower since the instrument is only looking at a small number of fragments (e.g. three fragments) during each scan. More scans can take place each second. Since only a few mass fragments of interest are being monitored, matrix interferences are typically lower. To improve the chances of reading a positive result correctly, the ion ratios of the various mass fragments are comparable to a known reference standard.