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.
Arrabito, G., Pignataro, B. (2011). Advanced Drug Screening platforms by Inkjet printing. In BOOK OF ABSTRACT XXIV Congresso Nazionale della Società Chimica Italiana.
Advanced Drug Screening platforms by Inkjet printing
Arrabito, Giuseppe Domenico;PIGNATARO, Bruno Giuseppe
2011-01-01
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.File | Dimensione | Formato | |
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