Molecular diagnosis of cancer using ambient ionization mass spectrometry

Kevin S Kerian, Purdue University

Abstract

My dissertation focuses on advancing the development and application of ambient ionization mass spectrometry methodology and technology to the biomedical field. The primary ambient ionization method used in my studies is desorption electrospray ionization mass spectrometry (DESI-MS) imaging, which has been previously used to analyze and differentiate disease state (i.e. tumor and normal) and in some cases tumor subtype of human liver, kidney, bladder, testicular, prostate, and brain cancers. DESI-MS imaging is an ideal method for disease diagnosis, because it can be used to directly correlate disease state with histopathology to develop and validate MS libraries built using the molecular profiles that relate to tissue disease states. The goal of this research is to use ambient ionization mass spectrometry for intraoperative surgical-guidance to more accurately diagnose tissue and reduce surgical times. Technological developments during the course of research revolved around touch spray ambient ionization mass spectrometry (TS-MS). This method uses a small probe (e.g. teasing needle) to pick up a minuscule amount of material from a sample, transfer the probe to the front of a mass spectrometer, and, with the addition of high voltage and solvent, induce ESI-like mechanisms for ionization. An evaluation of TS for its use as a potential in vivo surgical tool for disease screening was performed by concurrently studying prostate cancer tissue obtained from surgery with DESI-MS imaging. DESI imaging was used to first establish the relationship between MS molecular profiles and pathology which were then targeted using TS. Further, TS was also evaluated as a non-targeted technique by analyzing prostate specimens with unknown disease states and comparing the unknown data to the previously built MS targeted library. Methodological developments include DESI-MS studies for preliminary diagnosis of disease state and tumor subtyping using fine needle aspirations (FNA) of canine lymphoma specimens. Lipid profiles obtained from FNA samples were tested against a MS library built from a matched set of surgical tissue sections with disease states confirmed by histopathology. DESI-MS imaging was also used to expand upon previously investigated human kidney cancer. Previous investigations included two subtypes and low sample numbers (~10 paired normal and tumor samples per subtype), this more recent study includes the top three most commonly diagnosed subtypes (clear cell, papillary, and chromophobe) and higher sample numbers (~20 paired normal and tumor samples per subtype). In summary, many methodological and technological advances were made during the course of my dissertation studies. These advances include the development of a novel ambient ionization method, an extension of current applications to include FNA samples for early diagnosis, and an expansion of previous work to build more complex and comprehensive MS libraries. Advances such as these continue to propel ambient ionization mass spectrometry deeper into the biomedical field and gives hope to the use of chemical profiling using these methods for biomedical applications in the near future.

Degree

Ph.D.

Advisors

Cooks, Purdue University.

Subject Area

Analytical chemistry

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