History of Mass Spectrometry in Manchester – British Science Week

Author: Jayne Kirk

Mass spectrometry (MS) has long been known as a powerful analytical technique for the detection, determination and quantification of molecules. Today the technology is widely and routinely used to safeguard food and water supplies, protect the environment, diagnose diseases and drive pharmaceutical development. [1] Manchester (UK) has a long history of association with the technology and was home to the first commercial MS instrument. [2] In honour of British Science week, we are going back to our roots to explore the rich heritage of MS in Manchester. Read on to discover the fascinating journey that has brought this technology to the modern age and the remarkable discoveries that have been made along the way:

John Dalton

Atomic theory, isotopes and the Second World War

MS separates molecules based on their mass-to-charge (m/z) ratio, and could therefore be argued to have its origins in the development of atomic theory. It was the work of John Dalton, founding father of the Victoria University of Manchester, that led to atomic theory in 1805, in which he hypothesised that atoms of different elements had different relative weights. [3,4]

John Dalton Street Sign, Manchester; England; UK

Building on Dalton’s work, in 1910 Sir J.J. Thomson, discoverer of the electron in the 1890s, born in Manchester and alumnus of the forerunner to Manchester University, built the first instrument used to measure the m/z values of gaseous ionized atoms at Cambridge University. His research on neon gas showed the presence of isotopes with masses of 20 and 22 in an abundance ratio of 10:1. This work extended the use of the technology to the determination of exact atomic masses and quantitative analysis of elemental isotopes. Thomson’s student, Francis William Aston, continued the research and was behind the advent of the first double-focusing mass spectrometer in 1919. Aston’s research identified isotopes of chlorine, bromine and krypton. Both Thomson (Physics) and Aston (Chemistry) were awarded Nobel Prizes for their work within the emerging field of mass spectrometry in 1906 and 1922, respectively. [2,5]

Sir Joesph John Thomson

Mass spectrometry was also used in the Manhattan Project as a means of separating uranium isotopes for use in the first atomic bombs, although the approach was not used in the final production. Quantitative mass spectrometric analysis was also leveraged to measure reproducible compositions for refined hydrocarbons used as aviation fuel. [2,5]

Development of first commercial instrument

In the 1940s, the application of MS began to move away from solely academic work and into more practical fields. In recognition of this, the world’s first commercial MS instrument – the MS-1 – was developed by Metropolitan Vickers, a Manchester-based company. The technology made use of electron ionisation (EI). As might be expected, the instrument had a limited mass range of ~300 Da, and much lower mass resolution than today’s models. [2]

The low mass resolution became a problem in the early 1950s. Fragmentation patterns for small organic molecules were beginning to be understood, and there was a drive toward developing bigger and better instruments, Mass spectrometry remained focused on the analysis of small molecules, primarily owing to the limited number of approaches for getting compounds into the gas-phase. In the late 1970s, Barber and colleagues at UMIST (University of Manchester Institute of Science and Technology) developed Fast Atom Bombardment (FAB), a technique that allowed for the direct ionisation of biomolecules (peptides and proteins) without the need for chemical derivatisation. This technology was first commercialized by two Manchester companies: Kratos (Trafford Park) and VG (Altrincham), and brought mass spectrometry to a wider scientific audience including biochemists and biologists.[6]  

Since then, the field has exploded. [2,5] The transformative work carried out by these early MS pioneers set the stage for future innovations, and the field has continued to develop over the years since. Today, mass spectrometers designed, developed and engineered in Manchester are in use throughout the world. [3]

Modern Day MS in Manchester

With the city’s rich history in MS, it is no surprise to see that Manchester is home to many international companies specializing in the development of MS instruments – including the Waters Corporation Mass Spectrometry Headquarters in Wilmslow. The facility, opened by Chancellor George Osborne, has been designed and specially equipped to accelerate innovation in the field of MS. [1]

Recent advances in the field originating at Waters’ Manchester site include the advent of commercial travelling wave ion mobility-mass spectrometry (IMS-MS) instruments. By integrating MS with ion mobility spectrometry (IMS) – which separates molecules on the basis of size, shape and charge – the technology is provided with an additional dimension of resolution. In particular, IMS can be used to measure collisional cross section (CCS) values unique to each molecule in a sample. As CCS is correlated to sample shape, it provides an additional molecular parameter that helps distinguish between isomeric and isobaric compounds. The incorporation of IMS also serves to increase peak capacity and reduce spectral complexity, altogether simplifying data analysis. 

More recently, the development of the award-winning Cyclic IMS device in Manchester in 2019 was a breakthrough in the field. As resolution is proportional to instrument pathlength, by making the device circular, resolution can be increased with each pass while maintaining a compact size for the instrument. Furthermore, by introducing the ability to perform IMSn experiments in which ions of interest can be stored and selectively reinjected into the device, researchers can now effectively ‘zoom in’ on interesting parts of the spectra. The unprecedented control this offers is expected to usher in a new era of discovery within the MS research community. 

The future of the field

From the discovery of the underlying concepts behind the technology to the manufacture of the first commercial instrument, the city of Manchester has had a strong influence on events that have shaped the landscape of MS. By improving resolution, reducing spectral complexity and introducing the ability to perform IMSn experiments, recent advances in IMS-MS technology developed in Manchester are expected to facilitate a new generation of discoveries. Today, the city remains at the heart of innovation within the MS community, and it is anticipated that this will continue to be the case far into the future. 

Further reading:

  1. https://www.manchestereveningnews.co.uk/business/innovation/waters-corporation-unveils-new-wilmslow-7756662
  2. https://www.asms.org/docs/default-source/history-posters/vendor_vg-sectors_36x18.pdf?sfvrsn=e63576c3_0
  3. http://masses4masses.org
  4. https://www.dalton.manchester.ac.uk/about/
  5. https://www.annualreviews.org/doi/full/10.1146/annurev-anchem-061010-114018
  6. https://edu.rsc.org/feature/modern-mass-spectrometry/2020194.article