Advances in Bioanalytical Laser Ionisation Mass Spectrometry

Abstract

The use of secondary ion mass spectrometry (SIMS) for high spatial resolution qualitative mass spectrometry imaging (MSI) offers superior lateral resolution over competing technologies. There are however various caveats imposed for bioanalytical applications, extensive fragmentation and poor ion yields for high mass analytes both require redress. The development of cluster ion sources has increased sputter yields and reduced chemical damage, however the local chemical environment will often enhance or supress ionisation probabilities leading to inaccurate quantitative imaging. Laser post-ionisation sputtered neutral mass spectrometry (L-SNMS) offers the potential to overcome the sample matrix effect by essentially moving the ionisation process into the gas phase. Research is presented here that utilises various laser post-ionisation techniques with the main aim being to increase the available useful ion yields and decrease fragmentation. It was concluded that the 265 nm wavelength gave the best ion yields compared to the other wavelengths investigated for L-SNMS, enhanced ion yields were observed for key diagnostic fragments compared with Au+ SIMS for the pharmaceutics under investigation. The internal energies imparted onto neutrals sputtered by Au+, Au3+ and C60+ primary ion beams are investigated and it was confirmed that the extent of photofragmentation increased proportionally to the energy per nucleon of the primary ion beam projectile. Laser power dependence on the extent of fragmentation decreased as a function of energy per nucleon with sublimed gas-phase analytes having the lowest laser power dependence. Resonance ionisation mass spectrometry is investigated and applied to the analysis of key biological agents of interest. During the analysis of cisplatin it was discovered that an alternative two photon RIS scheme was possible for platinum (presumably a 2+1 scheme with Lambda 1 slightly detuned from the Pt resonance) and that this scheme was more efficient than the 3 photon scheme published in the literature. And finally the use of atmospheric pressure laser ionisation (APLI) for liquid chromatography/mass spectrometry (LC/MS) is investigated. In this research the application of femtosecond laser pulses to APLI is reported for the first time and compared with more mature LC/MS ionisation techniques.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Nicholas Lockyer (Supervisor) & Adam McMahon (Supervisor)