(15e) Piezoelectric-Based Spray Solvent Delivery System for Desorption Electrospray Ionization Mass Spectrometry: Design & Case Studies for High Throughput Reaction Screening
AIChE Annual Meeting
2018 AIChE Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Automation and High-Throughput Technologies for Pharmaceutical Discovery and Development
Sunday, October 28, 2018 - 4:50pm to 5:10pm
A Piezoelectric based Spray Solvent Delivery System (PieSDS) for high-throughput reaction screening using Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) is described herein. Our goal is to evaluate the effects of DESI spray solvents and solvent mixtures on the ionization efficiency of DESI-MS. Using PieSDS, two solvent flows are simultaneously and independently controlled at a precisely low target flow rate and are then mixed prior to spraying onto the DESI substrate. This spray-solvent is delivered from a pressurized reservoir whose pressure is rapidly and dynamically adjusted using a piezoelectric pressure controller and a feedback algorithm based on the measured flowrate downstream. The piezoelectric technology ensures a fast reaction time (< 40 ms) and a short settling time (< 1 s). In addition, a piezoelectric valve system, which can handle up to eight solvent combinations per device, enables a quick solvent switch within both solvent streams. The integrated system is controlled in a LabVIEW environment, where we employ a decoupling algorithm between the two solvent flowrate control loops for a faster and more stable flow after each setpoint change. The PieSDS with its control algorithm enables near instantaneous change in each solvent flow, which then allows for a solvent mixture concentration gradient and, in turn, fast screening of spray-solvent. Specifically, PieSDS varies the polarity and the physico-chemical properties of the solvent mixture during DESI-MS that then impacts the reactivity of the screened reactions through solvent effects in the charged droplets and the desorption mechanism of the reaction mixture from the DESI substrate. This maximizes the information obtained from a single DESI-MS experiment. PieSDS also opens a door for a novel application of reactive DESI via in-situ manipulation of reagent composition - the volume of spray solvent and the reaction mixture concentration can be varied simultaneously by flowing and changing a solvent in one stream and the reagent in another. This feature illustrates that PieSDS is a versatile solvent delivery system that is applicable to other automated, high throughput chemical reaction screening system beyond DESI-MS.