Mass Spectrometry Buying Guide

Mass Spec image

Buying a new mass spectrometer is a huge investment, and with the variety and diversity of mass spectrometers on the market, it is important to make sure you purchase the instrument that best fits your needs and will bring a good return for your investment.

This buying guide provides you with information to help you make the right decision when choosing new mass spectrometry equipment. Learn about common mass spectrometer configurations, key applications areas, different factors to consider for purchase, as well as current and future trends in mass spectrometry. Throughout the Guide, you will find Buying Guide Tips, which are practical suggestions that might help in your pursuit for the most suitable mass spectrometer. The Guide ends with a Glossary of acronyms that are mentioned in the text and some common terms in mass spectrometry that could be useful, especially for those who are new to the technology.


Introduction to Mass Spectrometry

Scientists across many disciplines use mass spectrometry to identify unknown compounds, elucidate structures, and quantify components in a sample, whether it is solid, liquid, or gas. A mass spectrometer measures the mass-to-charge ratio (m/z) of molecules (and/or its fragments) and atoms. The process involves1,2

  • Conversion of the sample into gaseous phase ions
  • Separation of the ions based on their m/z
  • Detection of the ions of each m/z
What's insite a mass spectrometer?

Figure 1 is a schematic of the different components of a mass spectrometer. The sample can be introduced in several ways, depending on the experimental set-up. It is common to couple separation techniques, such as GC, HPLC and CE, to a mass spectrometer. The choice of ionization source is extremely important. Ion sources are usually classified as “hard” or “soft” Hard ionization fragments molecules, whereas soft ionization offers little or no fragmentation.

Buying Guide Tip: When choosing an ionization source, consider the nature of your analyte(s) – polarity, solubility, thermal stability, molecular mass. Also, does your analysis (analyses) require fragmentation of the analyte?

The mass analyzer is the heart of the mass spectrometer. Choosing the right one is based on the application, cost and desired performance. The performance of mass analyzers is characterized by several parameters, such as the resolution, mass accuracy, sensitivity, mass range, and linear dynamic range. The next section of this Guide (Factors to Consider in Buying a Mass Spectrometer) has a more detailed list of these performance parameters.

Buying Guide Tip: Your application might not require the most powerful mass analyzer. Knowing your performance requirements based on your application(s) will help you make a cost-effective choice. (The more powerful the mass analyzers, the more expensive.)

Mass spectrometers are operated under high vacuum (~10-4 to 10-7 torr) to avoid collisions of the ions with other molecules. A computer controls the instrument, acquires and manipulates data, and compares spectra to reference libraries.

Mass spectrometer schematic

Figure 1. Components of a mass spectrometer. (Definitions of the ion sources and mass analyzers can be found at the Glossary found at the end of this guide)

Common Mass Spectrometer Configurations and Techniques

Although mass spectrometers can be used as standalone instruments, they are frequently combined with separation techniques to form powerful integrated systems such as GC-MS, LC-MS, IC-MS, and CE-MS. The type of inlet or sample introduction dictates the choices for ionization sources. For example, electron ionization (EI) and chemical ionization (CI) are used with GC. HPLC is usually coupled to electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI).

Buying Guide Tip: If you have an existing separations instrument (e.g. HPLC, GC) and want to couple it to a mass spectrometer, note that improved software integration and service support are achieved if both instruments are from the same vendor.

Coupling two mass analyzers in tandem (tandem MS, hybrid MS)3 is done to improve resolution, sensitivity, mass accuracy, and/or dynamic range. The difference between a tandem and hybrid MS is that the latter uses different types of analyzers for the first and second stages of mass analysis. Examples of tandem/hybrid MS are triple quadrupole (QqQ), quadrupole time-of-flight (Q-TOF), TOF-TOF, and quadrupole linear ion trap (QqLIT).

Factors to Consider: Applications

There are a number of common mass spectrometer configurations used in different applications both in research and routine analyses (see table 1).

Buying Guide Tip: Many manufacturers have applications laboratories where instruments can be demonstrated for potential customers, often using customer samples to demonstrate the instrument’s capabilities.

There are several kinds of ion sources and mass analyzers, but professionals in different fields tend to aggregate around specific configurations. For instance, in proteomics research, MALDI is a common ion source with TOF as the mass analyzer. MALDI is suitable for ionizing highly complex samples from protein-friendly buffers. The TOF is useful for its wide mass range capability. MALDI-TOF is also used in polymer analysis. In a more applied setting, such as a pharmaceutical QA/QC laboratory, there is a need to process samples more quickly than a basic research laboratory, and a comparatively small, defined set of analytes need to be detected/measured. In these types of laboratories, ESI with a triple quadrupole mass analyzer are commonly used.

Analyses of volatile and semi-volatile organics by GC-MS are carried out across many fields. Electron ionization is the most common and probably the standard form of ionization, while quadrupole is usually the mass analyzer (there are other options, of course). There are a several options for the analysis of non-volatile polar molecules, from stand-alone systems to the more commonly used LC-MS configuration. LC-MS is being used in many diverse applications, from research to routine analyses. (Common ionization sources and mass analyzers for LC-MS are found in Table 1). Organic molecules can also be analyzed using DART (direct analysis in real time). This instrument requires no sample preparation or significant method development, with potential applications ranging from forensics to food safety.

Applications where ultra-trace elemental analysis is required will use ICP-MS, for excellent sensitivity, throughput and dynamic range. In the past few years, ICP-MS has been coupled to HPLC and ion chromatography for speciation analyses.

Ion mobility spectrometry - mass spectrometry (IMS-MS) is a relatively new technique whose applications will continue to grow. It is currently used in proteomics and metabolomics, as well as pharmaceutical, environmental and chemical analyses4, to name a few. Although ion mobility spectrometry (IMS) has been around for 40-50 years, the first IMS coupled to a mass spectrometer became commercially available only a few years ago. IMS-MS offers additional selectivity, making separation of isomers, isobars, and conformers possible, as well as measurement of ion size.

Analyses that require high resolution use high-end mass spectrometers, such as FT-ICR and Q-TOF.

Buying Guide Tip: During your discussion with a mass spectrometer vendor, make sure you mention not only your target analyte(s), but also the sample matrix. Having a complete picture of your sample (target analytle and matrix) will help the vendor guide you in finding the best MS solution for your work.

Table 1. Popular mass spectrometry techniques/configurations used in different applications for research and routine analyses (Definitions of the acronyms can be found at the Glossary found at the end of this guide).

Target Analyte

MS technique/ configuration

Applications

 

Biomolecules

MALDI-TOF, MALDI-TOF/TOF, MALDI-FT-ICR

SELDI- TOF

Proteomics

Biomarkers

 

Proteins, peptides

LC-MS/MS (also nanoLC, capLC, UHPLC are used); stand alone MS

Common ionization source: ESI

Common mass analyzers: Ion trap, Triple quadrupole, FT-ICR, Q-TOF

IMS-MS (ion mobility)

 

Metabolites

GC-MS

Metabolomics

 

Stand alone MS: FT-ICR MS, TOF-MS, Q-TOF

LC-MS, GC-MS

Common ionization source: ESI

Common mass analyzers: Ion trap, Triple quadrupole, Q-TOF

Elements (metals, non-metals)

 

 

ICP-MS

LC-ICP-MS (or HPLC – ICP-MS)

 

Clinical

Environmental

Food and beverage

Geological analysis

Metabolomics

Materials science Semiconductor

SIMS

Materials science

Semiconductor

Ions

IC-ICP-MS (ion chromatography – ICP-MS)

Environmental

Food and beverage

Large organic molecules (e.g., polymers)

MALDI-TOF

ESI-TOF

Polymer products

Volatile and semi-volatile organics (thermally stable)

GC-MS

Common ionization source: EI, CI

Common mass analyzer: quadrupole, TOF, ion trap, triple quadrupole

Environmental

Criminal forensics

Food, beverage

Fragrance

Law enforcement, security

Sports, anti-doping

IMS-MS

DART

Non-volatile, polar organics (thermally labile)

(Reversed phase) LC-MS/MS (UHPLC also used); stand alone MS

Common ionization source: ESI, APCI, APPI

Common mass analyzers: quadrupole, ion trap, triple quadrupole, FT-ICR, Q-TOF

Clinical research and diagnostics

Environmental

Food and beverage

Metabolomics

Pharmaceutical

Sports, anti-doping

IMS-MS

DART


Factors to Consider: Performance, Features and Further Considerations

The specific features you need are based on the types of sample(s) you will be analyzing, and the type and quality of data you need to generate. Some features to consider include:

Abundance sensitivity - Ratio of the maximum ion current recorded at a specified m/z value to the maximum ion current arising from the same species recorded at a neighboring m/z value (IUPAC definition).5 By considering the abundance sensitivity of a mass analyzer, one can obtain an indication of the maximum range of analyte concentrations capable of being detected in a given sample.

Linear dynamic range - The range over which the ion signal is directly proportional to the analyte concentration.

Mass accuracy - The ratio of the mass-to-charge measurement error (that is, the difference between the measured M and the true M) divided by the true mass-to-charge. Usually quoted in terms of parts per million (ppm).

Mass resolving power/resolution - The capability to separate two neighboring ions peaks. Depending on the technology used, Full Width Half Maximum (FWHM) or 10 percent valley definitions of resolved peaks are used. Mass spectrometers that offer the higher end in resolution are also at the higher end in terms of cost (e.g., Q-TOF and FT– ICR).

Table 2 compares some features (figures of merit) of select mass analyzers.6

Table 2. Some performance features (figures of merit) of select mass analyzers

Feature (Figures of Merit)

Quadrupole

Quadrupole ion trap

TOF

FT-ICR

Abundance sensitivity

1x104 – 1x106

1x102 – 1x103

1x106

1x103– 1x104

Linear dynamic range

1x107

1x102 – 1x103

1x106

1x103– 1x104

Mass accuracy (ppm)

100

50 - 100

5 - 50

1 - 5

Mass range

4,000

4,000

> 100,000

> 10,000

Mass resolving power

100 – 1,000

1,000 – 10,000

1,000 – 40,000

10,000 – 1,000,000


Precision - The reproducibility with which ion abundances can be determined. External precision refers to reproducibility observed for measurements of nominally identical samples whereas internal precision refers to repeated measurements of the same sample.

Robustness/Ruggedness - The instrument is considered robust if it is constructed to operate reliably under expected process conditions that can include dust, solvent exposure, vibration, etc.

Sensitivity - This indicates the minimum quantity of analyte needed to produce a response in the mass spectrometer apparatus.

Speed - The time frame of the experiment is ultimately used to determine the number of spectra per unit time that can be generated.

Throughput - The capability to run large number of samples on a given time frame.

Buying Guide tip: Carefully consider which feature(s) is/are most important to you and are relevant to the needs of your laboratory. For example, mass range is far less important for elemental isotope ratio measurements than it is for protein molecular weight measurements, but the opposite can be said for precision or abundance sensitivity.

  • The need for tandem MS (or MS/MS) measurements

Tandem MS offers additional sensitivity and selectivity over single stage MS. The application, sample characteristics, and type of information you require from a mass spectrometer will dictate your need for either a single stage or tandem MS. Note that instruments that can do tandem MS are more expensive than single stage instruments.

  • Quantitative versus qualitative work

Quantitative analysis based on MS methods is usually carried out by hyphenated techniques (GC/MS, LC/MS) for organic molecules, and ICP-MS for elemental analyses. The most popular mass analyzer for quantitative work is the triple quadrupole (QqQ).

  • Routine measurement/ analyses versus research/R&D (non-routine)

In routine measurements/analyses, the method has been developed and established, and the mass spectrometer is expected to deliver results that can be trusted hour after hour, and day after day. Laboratories that carry out such analyses and have this expectation need a "workhorse" mass spectrometer. They need an instrument that gives a good combination of robustness, sensitivity and analytical range.

Flexibility to handle more advanced operations/applications is not a priority, unlike in the research or R&D setting.

  • Cost

When you consider the cost of buying and owning a mass spectrometer, bear in mind that it includes not only the bottom line purchasing cost, but also operation and maintenance costs.

  • Consider the users of the mass spectrometer

Will they need training? Consider ease of use of the instrument. The computer software controls the instrument, acquires data and processes data – how user friendly do you need it to be? Or do you need software that is more flexible, allowing you to do “more advanced” manipulations to extract higher quality information?

Buying Guide Tip: 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. Consistency in software layout is important, and saves time and training costs.

Buying Guide Tip: Some manufacturers offer kits that allow quick and efficient method development for specific applications (e.g., pesticides, forensics)

  • High level of service is important to avoid downtime

Service should be rapid and reliable. Instrument manufacturers usually offer service contracts. Customers with service contracts may receive priority in the schedule of the service engineer.

Current and Future Trends in Mass Spectrometry

Mass spectrometry is being used in every application area, from research to routine analyses. Currently, the triple quadrupole is the most popular technology, used in GC–MS, LC–MS, and ICP-MS. Triple quads have proven to be extremely good for quantitation of trace level analytes even in very complex samples, and as such, are used in a wide range of industries and applications, such as analyzing low-level contaminants in environmental water samples, detecting trace levels of pesticides and other health threats in foods, and quantitating key biological markers in the clinical sector. The high-end mass spectrometers – FT-ICR and Q-TOF – are typically used by the life science research sector, where high resolution is required in their research.

Regulatory requirements are, and will be getting more, stringent. The environmental sector uses ICP-MS for very low-level elemental analyses, since other techniques do not offer the same level of sensitivity. ICP-MS has become the standard technique for monitoring the quality of fluids used in microchips and other electronics that are incredibly sensitive to trace metal contamination. Work on LC-ICP-MS and IC-ICP-MS for speciation studies will continue.

The demand in clinical settings for mass spectrometers as medical devices that meet regulatory requirements continues. Manufacturers are making significant contributions to use MS technology from clinical research to the clinical diagnostics environment. Over the last several years they have been putting increased resources into gaining regulatory approval for their MS solutions for clinical use in different regions of the world. Many new mass spectrometry instruments are expected to be certified for routine use in the US and European Diagnostics markets in the next few years. In Europe and Canada, there are now a number of regulatory approved MS-based clinical diagnostic tests.

The interest in IMS-MS will continue to grow. There is still room for the technology to advance further. And as more commercial IMS-MS instruments become available, it will be more widely used in the analytical, biological, industrial and even clinical laboratories.

Indeed, mass spectrometry will continue to move forward, finding new applications and shaping new fields. It plays a major role in the research efforts towards personalized medicine. Clinical research using MS also continues to grow. In recent exciting news, a group in the UK developed an intelligent knife (iKnife) that can tell surgeons immediately whether the tissue they are cutting is cancerous or not. The iKnife is based on electrosurgery, wherein tissue is vaporized, creating smoke that is normally sucked away by extraction systems. The electrosurgical knife is connected a mass spectrometer to analyze the chemicals in the biological sample. Since different cell types produce metabolites in different concentrations, a biological sample can reveal a lot of detail about the state of the tissue. The iKnife can potentially be used in applications other than cancer diagnosis, such as identifying tissues with inadequate blood supply and the presence of certain bacteria in a tissue sample.

Summary

Mass Spectrometry is a powerful analytical tool that has demonstrated its great potential over the last decade, and will continue to shape the direction of many scientific disciplines. 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 a daunting task, and it is essential to keep scientific application, performance expectations, and budget in mind.

With such a fast moving technology, it is important to keep up to date with the latest advancements in technology. Sign up to the SelectScience Spectroscopy Newswire to receive the latest mass spectrometry news and use the SelectScience product directory, user reviews and application note library to make more informed decisions when purchasing new equipment.

Download a PDF version of the mass spec buying guide.

Acknowledgements

Glossary of Acronyms and Terms5

APCI - atmospheric-pressure chemical ionization; the ionization process occurs at atmospheric pressure through ion/molecule reactions

APPI - atmospheric pressure photoionization; atmospheric pressure chemical ionization in which the reactant ions are generated by photoionization

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.

DART – direct analysis in real time; it is a proprietary term indicating the formation of ions from a solid or liquid sample at atmospheric pressure through the interaction of a gas stream containing internally excited atoms or molecules with the surface

DESI – desorption electrospray ionization; formation of gas-phase ions from a solid or liquid sample at atmospheric pressure through the interaction of electrosprayed droplets with the sample surface

DIOS – desorption ionization on silicon; a variant of MALDI; sample is deposited on a porous silicon surface

EESI - Extractive electrospray ionization mass spectrometry; analytes are first evaporated/nebulized and then ionized by collision with the charged droplets generated by the ESI spray

ESI – electrospray ionization; the ionization process takes place at atmospheric pressure by passing a solution-based sample through a small capillary that is at a potential difference relative to a counter electrode

FAB - Fast Atom Bombardment; use high energy atoms to sputter and ionize the sample in a single step (like SIMS does); analyte is dissolved in a liquid matrix

FT-ICR - Fourier Transform ion cyclotron resonance; a type of ion trap mass analyzer based on the principle of ion cyclotron resonance in which an ion in a (very strong) magnetic field moves in a circular orbit at a frequency characteristic of its m/z value

Full scan – a mass spectrometer operation mode where a target range of mass fragments is specified; only ions in within this mass range will be detected. The determination of what range to use is largely dictated by what you expect to be present in the sample, while bearing in mind the solvent and other possible interferences. Full scan is useful in determining unknown compounds in a sample.

Hybrid mass spectrometer- a mass spectrometer that uses different types of analyzers for the first and second stages of mass analysis in tandem mass spectrometry; examples are Q-TOF, LIT-FTICR, Q-LIT

ICP-MS – inductively coupled mass spectrometry; an instrument that both atomizes samples into their constituent atoms and ionizes them to form atomic cations; highly sensitive for a range of metals and several non-metals; and provides information on isotopic distributions

IMS-MS – ion mobility spectrometry mass spectrometry; a combination of an ion-mobility spectrometer (IMS) and a mass spectrometer (MS); first the ion mobility spectrometer separates ions according to their mobilities; in the second step, the mass spectrometer separates ions according to their m/z

Ion trap – stores ions and manipulating the ions by using DC and RF electric fields in a se- ries of carefully timed events; common ion traps in mass spectrometry are linear ion trap, quarupole ion trap, orbitrap, ion cyclotron resonance

IRMS – istope ratio mass spectrometry

LIT-FTICR – a hybrid mass analyzer that combines linear ion trap (LIT) and FT-ICR

MALDI – matrix assisted laser desorption ionization; ions are produced by pulsed-laser irradiation of a sample that has been co-crystallized with a solid; used to analyze extremely large molecules

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.

m/z – mass-to-charge ratio; the dimensionless quantity formed by dividing the ratio of the mass of an ion to the unified atomic mass unit, by its charge number (regardless of sign)

Orbitrap – a trademark term for a type of ion trap (Kingdon trap); ions are orbitally trapped and oscillate harmonically along the trap axis; the oscillation frequency is inversely proportional to the square root of m/z

Q-LIT – a hybrid mass analyzer that combines quadrupole (Q) and linear ion trap (LIT)

QqQ – triple quadrupole; a tandem mass spectrometer composed of two transmission quadrupole mass spectrometers in series, with a (non-selecting) RF-only quadrupole (or other multipole) between them to act as a collision cell

Q-TOF – a hybrid mass spectrometer composed of a transmission quadrupole mass spectrometer (Q) coupled to an orthogonal acceleration time-of-flight mass spectrometer (TOF); a collision quadrupole is typically inserted between the two mass spectrometers

Quadrupole (mass analyzer)- an array of four parallel rod electrodes whose centers form the corners of a square and whose opposing electrode pairs are connected; ion are separated based on oscillations in an electric field created with the use of rf and DC voltages

Quadrupole ion trap (QIT) - often called just "ion trap"; a type of ion trap mass analyzer that confines ions using electric and/or magnetic fields and then selectively ejects ions of different m/z by ramping the rf voltage

SELDI – surface enhanced laser desorption ionization; a variant of MALDI in which the matrix is replaced by a surface coating designed to selectively retain proteins or peptides from a mixture depending on their physicochemical properties or biochemical affinity characteristics

SIM – mass spectrometer operation mode in which the abundances of ions of one or more specific m/zvalues are recorded rather than the entire mass spectrum. The detection limit is lower when doing SIM (compared to a full scan) since the instrument is only looking at a small number of fragments during each scan.

SIMS - Secondary Ion Mass Spectrometry; use high energy atoms to sputter and ionize the sample in a single step (like FAB does); used to study surface species and solid samples; no matrix is used

SNR or S/N – Signal to Noise ratio; a measure of a signal (peak) intensity relative to the baseline ("noise") level; for applications requiring high sensitivity, this needs to be very low

Tandem MS –also known as MS/MS or MS2 or MSn; involves multiple steps of mass spectrometry selection, with some form of fragmentation occurring in between the stages; can be accomplished with individual mass spectrometer elements separated in space or using a single mass spectrometer with the MS steps separated in time

TOF - Time-of-Flight; a mass analyzer that separates ions of different m/z by their time of travel between the ion source and detector, through a field-free region after acceleration by a constant voltage in the source (the ions will have differing velocities depending on their mass)

TOF/TOF – a tandem mass spectrometer composed of two TOF analyzers

References

  1. http://masspec.scripps.edu/mshistory/whatisms_details.php
  2. Lavagnini, I.; Magno, F.; Seraglia, R.; Traldi. P. Quantitative Applications of Mass Spectrometry. 2006. England: John Wiley & Sons Ltd.
  3. Glisha, G.L; Burinsky, D.J. J Am Soc Mass Spectrom 2008, 19, 161–172.
  4. Jiang, W.; Robinson, R.A.S. Encyclopedia of Analytical Chemistry, 2013, John Wiley & Sons
  5. Murray, K.K.; Boyd, R.K.; Eberlin, M.N.; Langley, G.J.; Li,L.; Naito, Y. Pure Appl. Chem. 2013, 85, pp. 1515–1609
  6. Mass Spectrometry in Polymer Chemistry (First Edition). Eds Barner-Kowollik, C.; Gruendling, T.; Falkenhagen, J.; Weidner, S. 2012, Wiley-VCH Verlag GmbH & Co. KG

Editor's picks

Kerry Parker

Editor-in-Chief

SYNAPT G2-S MS (Waters)

Product image

5 out of 5

"The mass spectrometer is easy to use and offers high mass resolution. The software is user-friendly. It is well worth the cost…"
Steven Linguenfelter, Wayne State University

Read more


NexION™ 300X ICP-MS (PerkinElmer)

Product image

4 out of 5

"The NexION is one of the best instruments that I have used. The ease of use on running samples and also on reprocessing samples is fantastic…”
Andrew Giles, Advanced Laboratories Ltd


Read more

AB SCIEX QTRAP® 5500 LC/MS/MS System (AB SCIEX)

Product image

5 out of 5

"This is a value for money system, rugged, robust system with low downtime and has high resolution. We have a system in our lab and it has wider applications in pharmacy and biology…"
Sunil Dubey, BITS


Read more

ultrafleXtreme™ (Bruker Daltonics)

Product image

4 out of 5

"Robust, easy to use, user friendly software. Compatible with diverse macro molecule applications..."
Saravanan Kumar, ICGEB



Read more

Thermo Scientific Orbitrap Velos Pro hybrid MS (Thermo Fisher Scientific)

Product image

4 out of 5

"We have had great experience so far with Orbitrap Velos Pro. It is stable and sensitive…"
Leila Afjehi-Sadat, Upenn



Read more


5977A Series GC/MSD System (Agilent)

Product image

4 out of 5

"I like this system very much because it is very easy to use and it usually works perfectly. Moreover it is perfect for our applications. In addition the software is very intuitive…”
Eva Porurull, University Rovira i Virgili

Read more