In a fast-paced pharmaceutical research environment, the operation of liquid chromatography mass spectrometry (LCMS) instruments in a "walk-up" or "open-access" selfservice mode is well-established . The LCMS continues to be the pivotal tool for not only monitoring chemical reactions, but also assessing the purity and/or integrity of the resulting products. Robust modern instrumentation aligned with an easy to use software interface enables rapid uptake from a diverse user group. Currently here in Pfizer, La Jolla, we operate six LCMS systems in this fashion for ca. 35 chemists running over 30000 samples a year with one expert analytical chemist assigned to monitor (calibration, response to errors, routine repairs etc.) these instruments. In this environment, the biggest variable in LCMS systems arises from numerous users assessing a wide array of different chemistries. Despite the users' attentive efforts towards sample preparation for analysis, often the sample's inherent physical and chemical properties lead to the major cause of instrument failure being clogging, which leads to the subsequent overpressurization and shutdown of the system. This problem has long been recognized and despite its apparent simplicity, it continues to plague this analytical technique particularly in a walk-up environment. Examination of our instrument performance metrics, which we have tracked since 2010, revealed that typically in a single year, 54% of our service calls to remediate instrument shutdown were directly linked to clogging by heterogeneous samples (Table & Supplmental Information, SI). This leads to several knock-on impacts for the administrator and users alike including; 1) reduced instrument capacity for users due to instrument down-time, 2) resource requirements for the administrator to troubleshoot, repair, and maintain the performance of the instrument, 3) potential cost of parts to repair the instrument if the component in which the source of the blockage is located cannot be cleaned out, and 4) pre-blockage, unreliable chromatography due to pressure spikes as debris builds up accompanied by sample carry-over leading to chemists potentially having to repeat LCMS experiments, or being unable to make decisions based on the analytical data obtained