Ambient Ionization Mass Spectrometry for Cancer Diagnosis and Surgical Margin Evaluation

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.

Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry

“…Note that an alternative method of molecular diagnosis of neurological tissue in the form of Raman spectroscopy is being developed concurrently (8,9). Both DESI-MS and REIMS have been applied to different organs (7,(10)(11)(12)(13)(14), generally with excellent disease discrimination via comparison with spectra of pathology-defined reference material. REIMS requires the use of special surgical procedures but gives real-time information.…”

Clinical Application of Ambient Ionization Mass Spectrometry

“…44) REIMS is one of the few AIMS methods which can be conducted in vivo, or operated under online conditions during experiments. 7) As a result, the introducing of REIMS to the surgical applications is served by combining mass spectrometry with clinical medicine.…”

“…7) In this review, we will highlight some of the most widely used AIMS modules and their applications in clinical realm (Table 1).…”

Clinical Mass Spectrometry—Achieving Prominence in Laboratory Medicine

“…Two reviews in this issue highlight new areas of opportunity for MS to expand its boundaries. One review provides information about direct tissue analysis and imaging (3 ), and the second covers new uses of ambient ionization in point-of-care diagnostics and other clinical measurements (20 ).…”