Novel Sampling Strategies for the Interrogation of Complex Samples Using Ambient Mass Spectrometry

Abstract

Complex samples – either due to physical structure or chemical components – often require extensive sample preparation to facilitate analytical interrogation. Ambient Ionization Mass Spectrometry (AIMS) offers a method of interrogation with minimal sample preparation, facilitated by direct analysis. However, AIMS workflows can still require sample pre-processing and specialist training, thereby reducing sample throughput, efficiency, and accessibility. The validity of AIMS techniques has already been proven by their widespread implementation, however, to extend the benefits of AIMS workflows to complex samples (e.g., uneven biological samples and powders), technique adaptations are needed. This would support the development of workflows that are minimally/non-destructive, rapid, facile, automated, and more efficient, while remaining accessible to personnel with varying degrees of technical training. Herein, a Liquid Microjunction – Surface Sampling Probe (LMJ-SSP) is modified to develop novel AIMS-based sampling platforms for complex samples, improving analytical accessibility for traditionally challenging sample types (e.g., uneven samples and powders). First, a modified LMJ SSP, the Coaxial Conductance Probe (CCP), was developed for the automated direct analysis of uneven surfaces. This conductance-based sampling approach facilitates automated sample contact detection, regardless of sample conductivity or surface topography. The CCP was validated using custom non-conductive models, then applied to the study of cell-line containing MatrigelTM cubes. Second, the CCP was used in conjunction with a custom multi-pellet die set to facilitate higher throughput screening of powdered products for Endocrine Disrupting Chemicals (EDCs). The development of the CCP facilitated the direct analysis of several complex samples, and shows potential to be used in a variety of applications. From the study of uneven samples, the CCP demonstrates considerable promise as a rapid, point-of-care device for direct MS analysis of topographically complex clinical samples, with potential applications such as histological margin assessment, cell culture screening, and rapid smear profiling. Meanwhile, the CCP paired with the multi-pellet die set presents a robust, automated platform for rapid screening of EDCs in powder based commercial products, with potential applications in quality control, regulatory compliance testing, contaminant detection, and drugs-of-abuse screening.