Mass spectrometry is used by scientists to analyze the chemical composition of a sample on an elemental level, giving often unrivalled detail about the species the user is dealing with. The simple principle which drives the technology is the use of an electromagnetic field to separate and select charged molecules or fragments, ions, depending on their mass to charge ratio (m/z), size and shape.

Although there are many types available, all instruments are typically composed of a sample inlet and ion source, a mass analyzer, and a detector; along with a data processing and user interface system. The appeal of commercial machines, as preferred to building your own, is often the ease of use, reliability and consistency that comes with intuitive user systems. Most of these systems combine different ion source and mass analyzer systems, appropriate depending on the user application; and are often used in conjunction with other analytical techniques, such as gas (GC) or liquid (LC) chromatography.

Whether you work in proteomics, environmental science, analytical chemistry, food science, drug discovery or other disciplines, this buying guide aims to provide the vital information needed to assist the decision making process.

When purchasing a mass spectrometer, there are a number of factors to consider. Firstly, you should think about your chosen application area. Proteomics, for example, will require a different setup to environmental or geological sample analysis. This may seem obvious, but as the power of commercial products increases, many more have multiple application uses. Considering your exact requirements will allow you to make an effective purchase, increasing the useful lifetime of the machine.

Cost and training are also contributing factors. GC-MS, for example, will be significantly cheaper to run than HPLC-MS, and might be most suitable if you work with volatile organic analytes. A different machine will likely be needed on the lab bench to the one in a dedicated analytical department, as staff have different expertise and requirements. The main manufacturers offer comprehensive industry service coverage across the range of instruments, and whilst expensive, this must be balanced against productivity outages and downtime.

Each section below talks you through the terms, technologies available and possible application areas.

As with all scientific equipment, each analytical tool has its own language. As we mentioned above, different applications will require varying accuracy, power and flexibility. Here are some of the terms to look for when comparing products and technologies.

Mass Range – This is the specified maximum range of masses (in m/z, atomic mass units or Daltons) that the instrument can cope with. Dealing with single elements in isotope ratio MS, for example, will not require a large range, but large organic molecules, polymers and proteins will need machines with a powerful mass range.

Mass Resolution - An indication of the resolving power (RP) of that instrument between two neighbouring ion peaks. Greater resolving power contributes to better confidence in the accuracy of results. Depending on the technology used, Full Width Half Maximum (FWHM) or 10 percent valley definitions of resolved peaks are used.

Mass Accuracy – The margin of error in operation for an instrument, the ability of an MS setup to resist deviation from the true mass to charge ratio in each case.

Sensitivity - This indicates the minimum quantity of analyte needed to produce a response in the spectrometer apparatus. This is important to bear in mind when working with complex matrices using gentle ionization techniques like MALDI or ESI (see below).

Dynamic Range – The range in which the sample ion strength is proportional to the signal output strength. This factor is important when searching for low level impurities, and increased scanning speeds of instruments in modern instruments contribute to maintaining sensitivity over a wider dynamic and mass range. Many current machines boast a 105 dynamic range.

SNR – Signal to Noise ratio. For sensitive applications, this needs to be very low, and with the sensitivity and capability of most products to be highly selective, some manufacturers view this as less of a good indicator of quality when comparing instruments. Current market spectrometers use damping gases, ion cooling and magnetic technologies to stablize ions, getting rid of neutral species or photons that create interference.

SIM/Full Scan – Selected Ion Monitoring or Full Scan mode. Many instruments work in both, either scanning through their entire mass range capability (Full Scan) or working with specific target ion masses (SIM), giving greater sensitivity and accuracy.

MRM/SRM – Multiple/Selected Reaction Monitoring. The ability to follow a specific reaction species or multitude through the collision or reaction cell, giving a clear spectrum suited for target analysis using tandem MS setups. Current market technologies are capable of scanning and following up to 500 species a second. See Triple Quadrupole instruments below for more details.

CID/ETD – Collisionally Induced Dissociation and Electron Transfer Dissociation are both key modes of dissociation within a collision or reaction cell, specifically important to MS-MS experiments.

A range of ionization methods are employed in modern mass spectrometry, and the choice of method heavily affects mass accuracy, resolution and sensitivity. Commercial MS systems give a broad range of options, and typically allow users to pair a number of ionization methods with the mass analyzer setup.

Method	Mass Analyzer	Description	Sample/Analyte	Application
Electron Impact (EI) / Chemical Ionization (CI).	Used commonly with a GC-MS setup using Ion Trap, single or triple quadrupole MS.	Volatilized sample bombarded with high energy electrons or reagent gas at high pressure.	Small organic molecules, non – polar, volatile but thermally stable.	Routine use in clinical research and drug discovery, food, environmental and hydrocarbon analysis, as part of GC-MS.
Atmospheric Pressure Chemical Ionization (APCI)	Used in liquid chromatography (LC-MS) setups.	Discharge creates ionic nitrogen species, which then collide with solvent and analyte vapour, creating predominantly single charged ions.	Use for complex matrices, but less polar that ESI. Limited by thermally unstable compounds.	LC-MS experiments, uses in metabolomics, drug screening and pesticides.
Atmospheric Pressure Photo Ionization. (APPI)	Used in LC-MS, or as in solvent assisted APPI as a source in Ion Mobility MS, whose modern machines use triple quadrupole mass analyzers.	Analyte molecules are ionized to a cationic (positive) radical by high energy photons.	Non polar compounds not suitable for ESI and APCI, for example, complex hydrocarbons. Useful with poor charge carrier solvents (hexane, isooctane etc).	Applications which demand a wide dynamic range, and low chemical noise. Useful for work on drug research, steroids and PAH's (polycyclic aromatic hydrocarbons).
Secondary Ion MS (SIMS)	Magnetic Sector -MS, TOF	Secondary surface analyte ions liberated as a result of sputtering; bombardment with high energy Xe+ / Ar+ ions. FAB uses a glycerol matrix and Xe species to similar effect. Can use negative ions and neutral species as well as positive, most commonly O- and neutral rare noble gases (non charged Xe/Ar).	This is a destructive method, which can result in a noisy spectrum, but is ideal for solid surfaces and thin film analyte/matrix samples.	Surface content analysis, alternately used with Fast Atom Bombardment (FAB). Analysis of films, paints, polymers, semiconductors and electronic materials.
Matrix Assisted Laser Desorption Ionization (MALDI)	Most commonly used with TOF (see below), TOF/TOF and triple TOF tandem setups.	Pico-molar amounts of analyte mounted onto an adhesive chemical matrix, then irradiated, causing soft ionization of sample for mass analysis.	Complex matrices, low level analyte concentrations. For example: polymers, biomolecules and proteins.	Proteomics and Pharmacokinetics, mass determination and sequencing of proteins, molecular weight characteristics of polymers.
Laserspray Ionization (LSI)	Used with Ion Mobility techniques. Orbitrap MS mass analyzer with LSI sources exist.	Laser ablation of analyte and matrix at atmospheric pressure, to obtain sample ions.	Can be used to give a selection of singly charged ions, similar to MALDI, or multiply charged species, like ESI.	Proteomics, de novo sequencing. Metabolite characterisation.
Electrospray Ionization (ESI)	TOF, Ion Trap, Quadrupole, FT-ICR MS	The softest ionization technique, a standard choice for LC-MS. Taylor cone and spray techniques develops high charge density droplets, aiding solvent evaporation to give intact ions for mass analysis.	Typically used in large m/z, molecular weight applications, involving protein folding, biomolecules and polymer analysis. The most versatile choice for polar compounds, like drugs, if low fragmentation is required.	Pharmacology, clinical research and drug development. Polymers, materials. Bioanalysis and protein sequencing, Metabolomics.
Field Desorption / Ionization (FD/FI)	GC-MS setups	Unlike other techniques, no primary beam is employed for ionization. FI uses heating to volatilize samples, which then experience a high gradient field. FD uses a filament emitter to make non-volatile samples available.	Good for thermally labile samples, such as organometallics, sugars, peptides and carbohydrates.	Liquid Injection Field Desorption Ionization (Linden CMS), allows automation of MS for sterically hindered, reactive organometallic samples, hydrocarbons matrices such as crude oil.

Time-of-Flight (TOF) MS

One of the most common setups, TOF mass spectrometers use a field-free region to separate ions after acceleration from the source. Modern machines use reflectron technology to provide accuracy, but the real advantage lies in the flexibility of TOF mass spectrometry, as the technology copes with high mass limits. Frequently used with GC-MS and LC-MS chromatography systems, many modern TOF setups employ quadrupole mass analyzers (Q-TOF), giving extra selectivity and power. Particularly useful for proteomics and biological analytical procedures, TOF is most commonly combined with ESI or MALDI ion sources. Companies like AB SCIEX specialise in tandem systems, like parallel TOF/TOF and Triple TOF systems, designed for protein imaging and MALDI experiments.

ICP-MS

Inductively coupled plasma-mass spectrometry provides a uniquely powerful tool for those needing the lowest detection limits (single parts per trillion) and greatest flexibility in elemental analysis. An increasing number of ICP-MS machines are used to detect trace metals in electronic semiconductor research, for example, or environmental and bio-monitoring applications.

Many of these machines use quadrupole mass analyzers, and can scan greater than 5000 amu per second, meaning the greatest range of elements and isotopes can be accurately and quickly separated, increasing user power and productivity. These machines provide reproducible clarity but using the instruments with quadrupole ion detectors, and using them in collision and reaction modes, is the best way to ensure very low interference. Universal cell technology means that you can use ICP-MS in both the modes, using a scanning quadrupole to minimize interference and maximize selectivity.

Orbitrap MS

Used with an LC-MS, Orbitrap employs a combination of ion trapping and collisional cooling, before analyzing a typical sample, separating components using axial oscillations of different frequencies, depending on the mass/charge ratio of the analyte species. This ion-current motion is then transformed into spectral data. With a typical mass resolution power of around 150,000, and very high mass accuracy of a couple of parts per million, this innovation can utilize a variety of ion sources and sample fragmentation techniques, rendering it ideal for a range of experiments, but particularly de novo protein sequencing and metabolite characterization.

Ion Mobility Q-TOF & IM-MS

For those areas of quantitative research that require very high accuracy as well as sensitivity, Ion Mobility MS might be the answer. In many areas of environmental or forensic research, for example, knowing exactly what species you have, and in what quantity, can be a legal essential. The current range of IM-MS can be used with a number of ion sources, for example ESI, MALDI, or laser spray (LSI), particularly useful in proteomics or pharmacokinetics.

The technology uses wave-guiding and quadrupole setups, along with gaseous modifier molecules to separate and differentiate between isobaric molecules, that is to say different molecules with the same weight and retention time. This allows scientists doing complex bioanalysis a great deal of control, discriminating between retention time, m/z and drift time in the TOF apparatus. This technology, like many others, can be used in combination with liquid chromatography (LC).

Quadrupole

Quadrupole mass filter systems are probably still the most common mass analyzers on the market. Routinely used as the mass analyzer of choice in LC or GC-MS and MS-MS (tandem), the quadrupole uses a radio frequency and direct current voltage with alternating polarities, sweeping a range to force ions of certain mass to resonate and pass through the filter. This gives high selectivity and mass range. Triple Quadrupole setups use several in tandem, to facilitate the selection and reaction of specific precursor ions, using MRM (see above). This technology is exploited in ICP-MS, and can be used with a Linear Ion Trap, sometimes branded a Q-Trap hybrid, giving real professional power to those working in drugs pharmacokinetics and protein quantitation.

Ion Trap

Linear and Quadrupole Ion Traps (LIT/QIT) trap charged species using a combination of a direct current and non-static alternating current in a quadrupole setup. Both used in Orbitrap MS, Quadrupole and LC or GC-MS setups, LIT has traditionally allowed for faster scan times. This setup stabilizes ions, using an inert damping gas, like nitrogen, to collisionally cool the analyte. Again, the control given means this apparatus is currently popular in machines for proteomics and analysis in the life sciences.

Isotope Ratio MS

Measuring the isotopic ratio of an abundant element, like carbon, oxygen or nitrogen allows you to determine the purity and quality of a sample. Like Liquid Chromatography MS (LC-MS), this technique is suitable for quality assurance and trace contaminant detection in the food, beverage and drug industries. Sensitivity and resolution is essential, and more of an issue than mass range, which tends to be between 1-150 Da at full power.

Fourier Transform MS (FT-ICR-MS)

Using a similar physical setup to an Ion Trap, FT-MS use superconducting magnets to detect ion movement in a dense field, giving very high mass accuracy and resolution, crucial for quantitative work with proteomics, biomarkers and sequencing. Current machines range up to 18 Tesla, and can use triple quadrupole technology for sensitive MS-MS and MRM work. For life science application areas, such as small molecule tissue imaging and 'top down' protein sequencing, modern FTMS machines work with a range of ion sources and core chromatography apparatus.

A word on software

Picking your mass spectrometer based on practicality and ease of use is essential, and most major manufacturers use similar, intuitive 'walkup' software interfaces across their range of machines. A good example is Agilent's MassHunter software, used with most MS systems the company designs. Consistency in software layout is important, and saves time and training costs.

It is also important to bear in mind the need for commercial database facilities, to cross reference work. New software also benefits from manufacturers embracing consumer technology and ideas. Shimadzu, for example, offer the use of open source PsiPort software with its GC and LC-MS systems, and AB Sciex has embraced the world of the smartphone with the MS iCalc, giving users a free app database and calculation tool to aid in breaking down and cross-referencing data.

Current trends show Orbitrap MS and Ion-Mobility to be very popular, with SIM and MRM being the terms to watch out for with detailed quantitation work.

Mass spectrometry has great diversity as an analytical tool, but future consumer technologies are most likely to be based around the quickly expanding worlds of proteomics and genomics, as the biopharmaceutical industry grows.

Manufacturers are constantly driving new technologies for applied areas, where ease-of-use, reliability and absolute quantitation are critical in the food, environmental and toxicology sectors. Powerful techniques are enabling toxicology researchers to move to an animal free, in vitro industry. Material science, for composites, polymers and electronics, also proves to be a growing area, where the accuracy of exemplar technologies like IS MS and ICP-MS are needed.

A number of manufacturers are spearheading a move to a use of the technology from clinical research to the clinical diagnostics environment. Many new mass spectrometry instruments are expected to be certified for routine use in the US and European Diagnostics markets in the next 3-6 years.

As well as being a tool for the future, mass spectrometry is also unique in its power for studying the past. Recently, researchers at the Biochemical Engineering Institute, Saarbruecken, Germany have been able to identify keratin strands within neolithic samples of the 53,000 year old iceman, Oetzi, using state of the art MALDI-TOF. This kind of species identification and characterization is a good example of the power of mass spectrometry.

Mass Spectrometry is a powerful analytical tool, with great potential. It is routinely used in all areas of science, from environmental health, food and drug development, to cutting edge materials, biological and electronics research. Choosing from the wide range of techniques and technologies available can be difficult, and it is essential to keep scientific application and budget in mind. As fashions change with such a fast moving technology, it may be helpful to use the SelectScience application guides and reviews. Signing up to the Spectroscopy Newswire from SelectScience, along with manufacturer mailing lists, is a good start for those looking to keep up to date.