Development and application of novel ionisation sources for mass spectrometry/ biological chemistry
Lead Research Organisation:
Swansea University
Department Name: Institute of Life Science Medical School
Abstract
The analysis of biomolecules such as carbohydrates, lipids, proteins and nucleic acid form plant and animal sources by mass spectrometry can be challenging due to the complex matrices in which they are found. The field of ambient desorption/ionisation (ADI) mass spectrometry offers the possibility to analyse some of these compounds requiring limited or no sample preparation.
To address these challenges a next generation compact plasma ADI source (termed GlowFlow) for mass spectrometry will be developed based on the atmospheric pressure glow discharge in the flowing afterglow mode design. The source will be to engineer so that it has good sensitivity as a qualitative analysis method, retaining the characteristics of a much larger but cumbersome prototype. It will be designed with a universal interface for a range of mass spectrometers and sample inlets addressing the lack of recognisable interfaces and reproducibility of existing designs.
The source will be used to study gas phase ion-molecule reactions and the characterised mechanisms of these reactions will be used to investigate suitable dopants to further enhance the source's ionisation efficiency. Due to the range of ionisation processes occurring in the plasma discharge the source will be suitable for the analysis of a wide range of sample chemistries' from polar to non-polar when compared to more conventional sources.
The source's ability to ionise a wide range of sample chemistries and its high sensitivity means it will find particular application in biological chemistry, as well as for small molecule pharmaceuticals, pesticides, explosives, and drugs of abuse. The mass spectrometry market is estimated to grow to over US$5 billion by 2022 and due to its compact design and integration with a range of inlets this new plasma-based source has the potential for commercialisation in the next generation of instruments.
EPSRC Research Areas:
Analytical science
Chemical biology and biological chemistry
Chemical reaction dynamics and mechanisms
Chemical structure
To address these challenges a next generation compact plasma ADI source (termed GlowFlow) for mass spectrometry will be developed based on the atmospheric pressure glow discharge in the flowing afterglow mode design. The source will be to engineer so that it has good sensitivity as a qualitative analysis method, retaining the characteristics of a much larger but cumbersome prototype. It will be designed with a universal interface for a range of mass spectrometers and sample inlets addressing the lack of recognisable interfaces and reproducibility of existing designs.
The source will be used to study gas phase ion-molecule reactions and the characterised mechanisms of these reactions will be used to investigate suitable dopants to further enhance the source's ionisation efficiency. Due to the range of ionisation processes occurring in the plasma discharge the source will be suitable for the analysis of a wide range of sample chemistries' from polar to non-polar when compared to more conventional sources.
The source's ability to ionise a wide range of sample chemistries and its high sensitivity means it will find particular application in biological chemistry, as well as for small molecule pharmaceuticals, pesticides, explosives, and drugs of abuse. The mass spectrometry market is estimated to grow to over US$5 billion by 2022 and due to its compact design and integration with a range of inlets this new plasma-based source has the potential for commercialisation in the next generation of instruments.
EPSRC Research Areas:
Analytical science
Chemical biology and biological chemistry
Chemical reaction dynamics and mechanisms
Chemical structure
Organisations
| Description | Since its development, electrospray ionization (ESI) for the analysis of thermally labile, polar compounds and particularly biomolecules has been extremely useful. Not all compounds can be easily protonated and electron ionization (EI) is still a widely used ionization method for compounds like hydrocarbons. However, the low-pressure environment of the EI source requires complex and expensive vacuum systems and inlets. Therefore, a source which can ionises non-polar compounds while operating at atmospheric pressure would be highly advantageous. In this thesis I have undertaken development and characterisation of four prototype atmospheric pressure glow discharge ionization sources for the analysis of compounds not normally amiable to ionization by conventional atmospheric pressure ionization sources. A helium micro-glow discharge source ("Prototype V") operated using a direct current power supply was studied and its discharge characterised. Its current-voltage relationship increased linearly which is typical of the abnormal glow regime while thermal imaging showed it had a "cold" discharge. Prototype V was successfully interfaced with a Xevo G2-S time-of-?ight and a Xevo TQ-S triple quadrupole (Waters Corp, Wilmslow, UK) and used with a range of sample introduction methods, initially a solids probe, but later APCI and ESI probes. These probes enabled prototype V to readily integrate with separation sciences; speci?cally liquid chromatography was demonstrated for complex mixture analysis. Prototype V exhibited high analytical sensitivity in the nanogram range in both positive and negative modes and could ionize a wide range of compound chemistries from polar to non-polar. In particular it showed sensitivity to non-polar compounds in negative-ion mode when compared to ESI. This gives the source the potential to operate in conjunction with a range of sample inlets and in combination with other ionization techniques as part of a multimodal platform to analyse the widest range of samples and a step towards a universal source. |
| Exploitation Route | Further research into the nature of the ion and neutral species in the electronic plasma. Development of a gas chromatography interface and further optimisation of source conditions. |
| Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |