Single-Cell Imaging of Exogenous Compounds Using Cluster Secondary Ion Mass Spectrometry

Restricted (Penn State Only)
Author:
Bloom, Anna Nichole
Graduate Program:
Chemistry
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
January 20, 2017
Committee Members:
  • Nicholas Winograd, Dissertation Advisor
  • Nicholas Winograd, Committee Chair
  • Barbara Jane Garrison, Committee Member
  • Joseph M Bollinger Jr., Committee Member
  • Esther Winter Gomez, Outside Member
Keywords:
  • Secondary Ion Mass Spectrometry
  • Single Cell Imaging
  • Chemical Imaging
  • Nanoparticles
  • Pharmaceutical Compounds
Abstract:
The focus of this work has encompassed analytical method development and application, specifically through the use of secondary ion mass spectrometry (SIMS) for the investigation of exogenous compounds in single cells. In particular, the goal has been to exploit the unique capabilities of SIMS in order to garner increased understanding of the interactions between pharmaceutical compounds and cellular systems to aid in the development of lower dose, more efficient medicinal compounds. The use of SIMS in biomedical applications is still a relatively young field. As such, work was devoted to pushing the boundaries of this technique to optimize conditions for single cell imaging using SIMS. It follows that proper sample preparation is of critical importance. The chemical and structural integrity of the sample must be maintained, while simultaneously allowing for compatibility in the ultra-high vacuum environment required for SIMS experiments. Compounds studied include fluorescent stains (Hoechst 33342 and DiI), gold nanoparticles of various shapes and sizes, several pharmaceutical compounds, and functionalized gold nanoparticles. Research of this nature has extensive applications, particularly in pharmaceutical compound development and understanding. The successes of the work shown here, highlights the ability of SIMS to be applied to better understanding the dynamics between drug, substrate, and host in targeted drug therapy applications.