Development and evaluation of matrix application techniques for high throughput mass spectrometry imaging of tissues in the clinic

Lennart R S Huizing; Shane R Ellis; Bart W A M M Beulen; Florian P Y Barré; Paul B Kwant; Rob J Vreeken; Ron M A Heeren

doi:10.1016/j.clinms.2019.01.004

Development and evaluation of matrix application techniques for high throughput mass spectrometry imaging of tissues in the clinic

Clin Mass Spectrom. 2019 Jan 28:12:7-15. doi: 10.1016/j.clinms.2019.01.004. eCollection 2019 Apr.

Authors

Lennart R S Huizing¹, Shane R Ellis¹, Bart W A M M Beulen², Florian P Y Barré¹, Paul B Kwant², Rob J Vreeken^{1

3}, Ron M A Heeren¹

Affiliations

¹ The Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
² Instrument Development Engineering and Evaluation, Engineering Department, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
³ Janssen R&D, Turnhoutseweg 30, 2340 Beerse, Belgium.

Abstract

Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a sensitive label-free technique that can be used to study a wide variety of clinical phenotypes. In this context, MSI offers huge diagnostic potential by supporting decision making in the determination of personalized treatment strategies. However, improvements in throughput and robustness are still needed before it finds a place in routine application. While the field has seen tremendous improvements in the throughput of data acquisition, robust and high-throughput sample preparation methods compatible with these acquisition methods need to be developed. To address this challenge, we have developed several methods to reduce the matrix application time to less than 5 min, while maintaining sensitivity and reproducibility. Workflows incorporating these methods provide a pipeline analysis time for MSI sample preparation and acquisition of less than 30 min. The reduced time for these analyses will contribute towards the integration of MSI into routine molecular pathology for clinical diagnostics.

Keywords: CHCl3, chloroform; DHB, 2 5-dihydroxybenzoic acid; Da, Dalton; FT-ICR, Fourier transform ion cyclotron resonance; FT-MS, Fourier transform mass spectrometry; FWHM, full width at half maximum; H&E, hematoxylin and eosin; ITO, indium tin oxide; MALDI, matrix assisted laser desorption ionization; MSI, mass spectrometry imaging; MeOH, methanol; NRM, norharmane; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; Pa, Pascal; Ppm, parts per million; RSD, relative standard deviation; S/N, signal-to-noise ratio; SM, sphingomyelin; TFA, trifluoroacetic acid; TIC, total ion count; TOF, time-of-flight; V:V, volume concentration; e.g, exempli gratiā; i.e, id es; m/z, mass over charge ratio; mBar, milliBar.