Chemical QuantArray: A Quantitative Tool for Mass Spectrometry Imaging
Sylwia A. Stopka, Daniela Ruiz, Gerard Baquer, Clément Bodineau, Md Amin Hossain, Valentina T. Pellens, Michael S. Regan, Olivier Pourquié, Marcia C. Haigis, Wenya L. Bi, Shannon M. Coy, Sandro Santagata, Nathalie Y. R. Agar, and Sankha S. Basu
PMID: 37469028 | DOI: 10.1021/acs.analchem.3c00803
Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is a powerful analytical technique that provides spatially preserved detection and quantification of analytes in tissue specimens. However, clinical translation still requires improved throughput, precision, and accuracy. To accomplish this, we created “Chemical QuantArray”, a gelatin tissue microarray (TMA) mold filled with serial dilutions of isotopically labeled endogenous metabolite standards. The mold is then cryo-sectioned onto a tissue homogenate to produce calibration curves. To improve precision and accuracy, we automatically remove pixels outside of each TMA well and investigated several intensity normalizations, including the utilization of a second stable isotope internal standard (IS). Chemical QuantArray enables the quantification of several endogenous metabolites over a wide dynamic range and significantly improve over current approaches. The technique reduces the space needed on the MALDI slides for calibration standards by approximately 80%. Furthermore, removal of empty pixels and normalization to an internal standard or matrix peak provided precision (<20% RSD) and accuracy (<20% DEV). Finally, we demonstrate the applicability of Chemical QuantArray by quantifying multiple purine metabolites in 14 clinical tumor specimens using a single MALDI slide. Chemical QuantArray improves the analytical characteristics and practical feasibility of MALDI-MSI metabolite quantification in clinical and translational applications.