Predicting Outcomes of Impingement-Based Mass Spectrometry Imaging

Abstract A physics-based scaling framework to predict the outcomes of impingement-based mass spectrometry imaging (MSI) techniques is presented to understand the underlying mechanisms and guide performance improvements. Particular emphasis is placed on analyte extraction, the fundamental process that defines MSI resolution and the softness of ionization. Two distinct regimes, thermodynamic (passive) and kinematic (active), are identified that follow different physical laws. Thermodynamic desorption arises under conditions approaching thermal equilibrium, where molecules are extracted through favorable energetic interactions with the solvent phase. In contrast, kinematic desorption occurs when high-energy particles or droplets impact the sample, supplying mechanical energy to overcome the cohesive forces that bind molecules at the surface. A dimensionless parameter is developed that compares the stress generated by an impacting particle to the cohesive forces binding molecules within a sample, providing a criterion for identifying transitions among extraction regimes. Through a scaling analysis of charged particle transport and impact dynamics, this parameter is expressed in terms of experimentally controllable inputs, revealing that kinematic extraction becomes possible only when the accelerating electric force exceeds the combined effects of the aerodynamic drag and particle inertia. Application of the methodology to representative MSI techniques yields predictions consistent with experimentally observed extraction behaviors, which supports the proposed mechanistic interpretation. More broadly, this framework establishes a semiquantitative foundation for predicting molecular extraction across a wide range of solution- and impingement-based MSI platforms, enabling systematic exploration of performance limits and guiding the design of next-generation MSI technologies using fundamental experimentally measured properties.