Advanced Drug Screening platforms by Inkjet printing

Abstract

In this work, we show a low-cost, speed, microarray-based drug screening platform that employs inkjet printing drug dispensing on an enzymatic-rich surface. Mixtures of a model substrate (Dglucose)/ inhibitor (D-glucal) couple have been inkjet printed on a target enzymatic monolayer (glucose oxidase) linked to a functionalized silicon oxide solid surface [1]. It has been possible to fabricate microarrays with quality factors as high as those of conventional pin printing spotting. By a simple horseradish-based colorimetric enzymatic assay, the detection of biological activity at the single spot has been proved. The figure shows a scheme of the platform: molecular inks of the enzymatic substrate or a substrate/inhibitor mixture are dispensed on the enzymatic-rich surface with detection at the single spots. Optical intensity measurements showed a competitive inhibition mechanism at the solid-liquid interface, along with overcompeting effects at lower inhibitor concentrations [2]. This methodology is extended to CYP450 enzymes like CYP3A4, one of the main targets for the phase I drug metabolism. In this respect, sol-gel enzymatic encapsulation strategies inside a polymer matrix prepared by MTMOS (methyltrimethoxysilane) precursors [3] or alginate are envisioned. The evaluation of the biological activity is realized via a fluorescent-based assay. In conclusion, we show how inkjet printing methodologies may investigate interesting physicochemical activities of functional biomolecules at a solid surfaces including their interaction and reaction behavior. Moreover, if coupled with a simple and generalized detection method they may satisfy speed, low-cost, miniaturized and high-throughput screening needs by dispensing entire chemical libraries on solid supported biological targets.