Development and biomedical applications of solid phase micro-extraction (bio-SPME) chemical biopsy devices

Abstract

Micro-sampling is a vital component in modern diagnostics and personalized medicine. In vivo SPME is a novel branch of biomedical applications of SPME (Bio-SPME) that offers unique advantages complementary to existing in vivo micro-sampling techniques such as micro tissue biopsy and microdialysis. When coupled with powerful modern detection methods, such as mass spectrometry, the minimally invasiveness and convenient sample-cleanup of in vivo chemical biopsy SPME enable the rapid analysis of exogenous and endogenous analytes from a biological system in vivo. In vivo SPME has seen success in numerous clinical applications from therapeutic drug monitoring (TDM) to untargeted metabolomic/lipidomic fingerprinting. While the scope of theoretical considerations extends deep into the realm of complex physical chemistry, bio- SPME and in vivo SPME can still be executed by medical personnel with limited theoretical knowledge as long as a few key experimental parameters are controlled, such as extraction time. Chapter 2 details the fabrication of a novel recessed SPME chemical biopsy probe and a push-pull microsyringe sampling device. Compared to conventional in vivo sampling tools, the latest devices offer superior physical robustness with a convenient chemical sorbent that does not require solvent activation. Such devices have been successfully implemented in human in vivo studies which are also included in this chapter. Chapter 3 presents a proof-of-concept study showing the importance of non-destructive sampling (ie. in vivo SPME) in untargeted metabolomics using ovine lung tissue as a model coupled with a commercial metabolomics kit. Chapter 4 is another proof-of-concept study which explores the applicability of bio-SPME in proteomics which was thought to be impossible. Various sample preparation and device fabrication strategies such as protein digestion and porous coating were employed to achieve protein identification in clinical SARS-CoV-2 patient saliva samples. Chapter 5 of the thesis addresses some of the flaws with previous in vivo applications of SPME, provides strategies to overcome them, and showcases numerous clinical in vivo applications with the improved calibration strategies. In short, this thesis work offers a comprehensive strategy for various in vivo and ex vivo bio-SPME applications.