Abstract
BACKGROUND: There is a clinical need for new technologies that would enable rapid disease diagnosis based on diagnostic molecular signatures. Ambient ionization mass spectrometry has revolutionized the means by which molecular information can be obtained from tissue samples in real time and with minimal sample pretreatment. New developments in ambient ionization techniques applied to clinical research suggest that ambient ionization mass spectrometry will soon become a routine medical tool for tissue diagnosis. CONTENT: This review summarizes the main developments in ambient ionization techniques applied to tissue analysis, with focus on desorption electrospray ionization mass spectrometry, probe electrospray ionization, touch spray, and rapid evaporative ionization mass spectrometry. We describe their applications to human cancer research and surgical margin evaluation, highlighting integrated approaches tested for ex vivo and in vivo human cancer tissue analysis. We also discuss the challenges for clinical implementation of these tools and offer perspectives on the future of the field. SUMMARY: A variety of studies have showcased the value of ambient ionization mass spectrometry for rapid and accurate cancer diagnosis. Small molecules have been identified as potential diagnostic biomarkers, including metabolites, fatty acids, and glycerophospholipids. Statistical analysis allows tissue discrimination with high accuracy rates (>95%) being common. This young field has challenges to overcome before it is ready to be broadly accepted as a medical tool for cancer diagnosis. Growing research in new, integrated ambient ionization mass spectrometry technologies and the ongoing improvements in the existing tools make this field very promising for future translation into the clinic.