Desorption electrospray ionization mass spectrometry (DESI-MS) is a powerful tool for ultra-high throughput chemical reaction screening having enormous scientific and practical implications. DESIMS enables considerably faster chemical reaction and/or product discovery than most current screening methods using very small amount of materials. It has the advantage of bringing the reagents in contact inside charged micro-droplets, that can accelerate reaction by compared to bulk or flow reaction approaches. Since both the desorption efficiency from the surface and the reaction kinetics can be significantly influenced by the DESI spray solvent flowrate and composition, these parameters are expected to play key roles in the overall performance of the ultrahigh-throughput screening. Syringe pumps are frequently used to deliver the DESI spray. They are robust, but inflexible and slow when it comes to manipulating solvent composition and varying flowrate setpoints. This study addresses the importance of designing a high performance, flexible solvent delivery system that enables more rapid solvent composition and flowrate setpoint changes than the routinely used syringe pumps. Our system utilizes a piezoelectric-based pressure controller and valve system employed with fine-tuned adaptive proportional-integrative-derivative (PID) controller. N-alkylation reactions were used to demonstrate the impact of spray-solvent composition and flowrate on the DESI-MS outcome. In particular, the results showed that ions resulting from solvent mixtures can induce reactions that would be otherwise unobserved when using the corresponding neat solvents. This further signifies the need for a flexible spray-solvent delivery system with fast dynamics in the context of ultra-high throughput DESI-MS analysis. (C) 2018 Elsevier Ltd. All rights reserved.