Award Recipient Learns Imaging Mass Spectrometry Techniques

Submitted by Jephte Akakpo, BS, MS

Imaging mass spectrometry (IMS) is a fairly novel technique enabling sensitive identification of drugs and metabolites from 2D samples, typically tissue sections. To learn this technique, I attended an advanced imaging mass spectrometry (AIMS) laboratory course at Vanderbilt University through the support of SOT’s Diversity Initiatives Endowment Career Development Award.

The objective of this course was to receive technical and hands-on experience in the critical steps of tissue preparation, tissue sampling, and data analysis in matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry as well as desorption electrospray ionization (DESI). Other IMS approaches such as laser capture micro-extraction, tissue micro-extraction, and hydrogel digestion/extraction were also introduced. I was fortunate to learn how to optimize parameters for tissue imaging using highly sensitive mass spectrometry instruments with high resolving power such as the Ion trap and the FT-ICR.

I had a key interaction with one of the pioneers in the field of IMS, Dr. Richard Caprioli, who is the director of the Mass Spectrometry Research Center at Vanderbilt University. His talk dealt with general considerations about IMS and provided insights about sample preparation and emphasized technological advances. Interactions with leading instrument vendors for on-site instrument demos took place with Bruker, Waters, HTXImaging, and Thermo Fisher Scientific. Hands-on workshops allowed me to interact with experienced faculty members and graduate students in the mass spectrometry department.

The experience allowed me to gain skills in sample preparation including fresh frozen tissue cryosectioning, washing/staining, formalin fixed paraffin embedded (FFPE) tissue sectioning, and antigen retrieval/washing. I also acquired skills in matrix application including manual spray coating, sublimation, TM Sprayer-matrix, and trypsin use. Finally, I gained skills in data processing with software such as Image Fusion, PIMS, SCiLS, and R/Cardinal.

My institution, the University of Kansas Medical Center (KUMC) Department of Pharmacology, Toxicology & Therapeutics (PTT) Analytical Core laboratory, recently acquired a Prosolia 2D DESI imaging stage for its Hybrid Q-ToF mass spectrometer. I am currently using the DESI imaging system with the goal to assess the qualitative and quantitative distribution of acetaminophen (APAP) and its subsequent biotransformed metabolites directly from cryo-sections of liver tissues after APAP overdose.

Three expected outcomes that the AIMS experience will help me achieve in the next 12 months are:

  • Optimizing liver tissue preparation and IMS instrument settings and generating IMS intensity imaging of analytes of interest,
  • Familiarizing myself with data mining algorithms and computer programming for data processing and imaging using our software (MSI reader), and
  • Obtaining a spatio-temporal IMS intensity distribution map of APAP-glucuronide.

The unique experience in this cutting-edge technology along with the critical thinking and problem-solving skills I am acquiring in my PhD training will allow me to successfully build a career in analytical toxicology. In addition to working on accomplishing the aforementioned goals, I regularly attend career professional development workshops at KUMC (ASCEND) as well as SOT Annual Meetings, which will help with building a network of professionals and assist me in my career transition from an effective PhD candidate to an outstanding postdoctoral fellow and finally an exceptional clinical and translational toxicologist.

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