The use of SIMS for high spatial resolution qualitative Mass Spectrometry Imaging (MSI) applications is without question one of the most powerful techniques currently available. There are however various limitations that pose challenges for bioanalytical applications. SIMS as a technique for quantitative MSI is often severely challenged when screening for biological analytes present in different sample matrices, the gas phase basicity of the analyte and or matrix will have a profound effect on the ionisation probability leading to incorrect quantitation [1].

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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 [2]. The high spatial resolution associated with SIMS is retained with the possibility of enhancement due to the increased ionisation probability associated with photoionisation [3, 4].

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This work aims to compare and contrast the analytical capabilities of SIMS with L-SNMS in terms of the maximum linear dynamic range, limit of detection and the limit of quantitation. A variety of small biological molecules of interest such as simple peptides, drugs and metabolites are analysed in a variety of tissue mimics of different chemistry. The photionisation and fragmentation characteristics are reported as a function of the laser intensity, pulse width and wavelength.

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[1] E. A. Jones, N. P. Lockyer, J. Kordys, and J. C. Vickerman, “Suppression and enhancement of secondary ion formation due to the chemical environment in static-secondary ion mass spectrometry.,” J. Am. Soc. Mass Spectrom. (2007) 18, 1559–67.

[2] G. Karras, N.P. Lockyer “Quantitative Surface Analysis of a Binary Drug Mixture - Suppression Effects in the Detection of Sputtered Ions and Post-Ionized Neutrals” J. Am. Soc. Mass Spectrom. (2014) 25, 832-840.

[3] A. Kucher, L. M, Jackson, J. O. Lerach, A. N Bloom, N. J. Popczun, A. Wucher and N Winograd “Near Infrared (NIR) Strong Field Ionisation and Imaging of C₆₀ Sputtered Molecules: Overcoming Matrix Effects and Improving Sensitivity” Anal. Chem., (2014), 86, 8613-8620

[4] B. J. Tyler, S. Dambach, S. Galla, R. E. Peterson, and H. F. Arlinghaus “Investigation of the Utility of Laser-Secondary Neutral Mass Spectrometry for the Detection of Polyaromatic Hydrocarbons in Individual Atmospheric Aerosol Particles” Anal. Chem., (2012), 84, 76–82

A significant proportion of material ejected from the sample surface during a secondary ion mass spectrometry (SIMS) experiment are neutral species and the large amount of information that they contain remain undetected [1]. Laser post-ionization (LPI) can access this information by intercepting the ejected plume with pulsed radiation, which in turns ionizes those previously neutral species. Strong-field ionization (SFI) proves our most versatile method of LPI, utilizing mid-infrared, femtosecond pulses to produce an electric field stronger than the Coulomb potential of organic molecules. This allows electrons to escape through barrier suppression or tunnelling while minimizing photofragmentation [2-4]. Our goal is to establish a method for separating the collision-induced damage from photofragmentation produced by the LPI pulse. Multiple wavelengths in the mid-IR are used in SFI of the gas phase, which establishes a photofragmentation pattern for each wavelength. A primary ion beam is then introduced, which also produces collision-induced fragmentation in addition to further photofragmentation resulting from higher internal energies within the sputtered molecule.

[1] Winograd, N. Analytical Chemistry1993, 65, 622A.

[2] Keldysh, L. Sov. Phys. JETP1965, 20, 1307.

[3] Willingham, D.; Kucher, A.; Winograd, N. Chemical Physics Letters2009, 468, 264.

[4] Lezius, M.; Blanchet, V.; Rayner, D. M.; Villeneuve, D. M.; Stolow, A.; Ivanov, M. Y. Physical Review Letters2001, 86, 51.