Electrochemical reactions on-chip : combinations with mass spectrometry for drug screening and proteomics

Abstract

This thesis is part of the "Nanopatterned Electrode Surfaces for Proteomics, Drug Screening and Synthesis" project led by the principal investigator Mathieu Odijk from the University of Twente (UT) in close collaboration with Hjalmar Permentier and Rainer Bischoff from the University of Groningen (RUG). It is funded by the Dutch technology foundation "Stichting voor de Technische Wetenschappen" (STW). In 2017, the STW was reorganised to become "Toegepaste en Technische Wetenschappen" (TTW), one of the three research domains of the Dutch national research council "Organisatie voor Wetenschappelijk Onderzoek" (NWO). The research project follows up on a previous one that resulted in several publications combining microfluidic electrochemical (EC) methods with liquid chromatography (LC) and mass spectrometry (MS). 1-3 In its current iteration, the project collaborates with the University of Groningen (RuG) and the two investigators Rainer Bischoff and Hjalmar Permentier. Additional collaborators are Albert van den Berg (UT), Wouter Olthuis (UT), Sonia García Blanco (UT) as well as Uwe Karst (University of Münster) and the companies Antec Scientific, Lionix International B.V., and Bronkhorst High-Tech B.V. The project aims to develop new nano-patterned surfaces with integrated waveguides in order to integrate spectroscopic methods into the previously mentioned microfluidic EC-LC-MS methods. It envisions devices capable of surface-enhanced infrared absorption spectroscopy (SEIRAS) and/or surface-enhanced Raman spectroscopy (SERS), in order to observe the reactions taking place inside the microreactor, possibly in real-time. The desired applications of these methods are the synthesis of added value fine chemicals, drug metabolism mimicry and protein analysis, all on the microfluidic, integrated scale. The last two applications are part of the research work presented in this thesis. Thesis ambitionIn the following, the applications drug metabolism mimicry and protein analysis are briefly explained, their problems stated, and solutions proposed. Lastly, research goals for this thesis are derived from the proposed solutions. The two main ones for total protein analysis are top-or middle-down 20,21 and bottom-up / shotgun proteomics 22,23 , as shown in Figure 1.2, reused from GREGORICH ET AL. 19 The abbreviations MS/MS, protein ID and PTM refer to tandem mass spectrometry, protein identification and post-translational modification, respectively. Both approaches include sample processing steps such as separation via liquid chromatography (LC) and In this chapter, co-authored by Jasper Lozeman and Pascal Führer, an overview of recent advances in a selection of spectroelectrochemical (SEC) methods is given and critically discussed before giving recommendations for advancements. The selection comprises the combinations of electrochemistry with infrared and Raman spectroscopy, written by Jasper Lozeman, and nuclear magnetic resonance (NMR) spectroscopy as well as mass spectrometry, written by Pascal Führer.