Expanding the Capabilities of Paper Spray Mass Spectrometry: High-Throughput Drug Screening and On-Paper Electrokinetic Stacking

Abstract

Paper spray mass spectrometry (PS-MS) offers advantages in simplicity and rapid analysis but faces challenges that have limited its widespread adoption. These include insufficient sensitivity for certain analytes, susceptibility to matrix effects in complex samples, and inconsistent quantitative performance. Such limitations have restricted the application of PS-MS in fields requiring high sensitivity in analysis of complex biological matrices. This dissertation explores approaches to enhance the capabilities and applications of PS-MS, with a particular focus on overcoming sensitivity limitations. Chapter 2 demonstrates the potential of PS-MS in forensic toxicology through an automated high-throughput urine drug screening method. Chapter 3 investigates the negative impact of laser cutting paper spray substrates on sensitivity and provides practical remedies. The core of this work revolves around the development and application of electrokinetic stacking coupled to PS-MS. Chapter 4 describes the integration of field-amplified sample stacking and faradaic ion concentration polarization into paper-based MS ionization cartridges. Chapter 5 presents mathematical modeling to complement the experimental work, offering a theoretical framework for understanding system behavior. Chapter 6 demonstrates practical applications of the technique, utilizing stacking devices to detect low levels of per- and polyfluoroalkyl substances (PFAS) in tap water and drugs of abuse in urine. These applications demonstrate substantial enhancements in sensitivity over conventional PS-MS, while preserving the technique's advantage of minimal sample preparation. Moreover, this work also identifies a potential path towards incorporating electrokinetic separations in PS-MS, addressing a longstanding limitation of the technique and potentially broadening its applicability in complex sample analysis.