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

In the pursuit of developing new tools for drug development and analytical proteomics, this thesis deals with research questions regarding fast drug metabolism mimicry and streamlined proteomic workflows. Both of these questions are present in current life science applications, where a lot of time and effort are spent that can be significantly reduced through modern, integrated and electrochemical on chip solutions.
This thesis presents the potential of electrochemistry hyphenated to spectroscopic and spectrometric methods by means of a critical literature review. It also showcases one such, complex method, namely chip electrochemistry hyphenated to trapped ion mobility spectrometry followed by a time of flight separation in a high resolution mass spectrometer (chipEC TIMS ToF HRMS) at the example of phase I and II mimicry of ethoxyquin and paracetamol. The electrode material boron doped diamond (BDD) has shown good qualities for metabolism mimicry and oxidative peptide cleavage in recent years and was further investigated for biofouling occurring in a simple chip. The chips were fabricated with an adhesive tape as fluidic patterning and bonding agent, exploring new fabrication techniques for a more streamlined chip development. Lastly, a new complex chip design incorporating three subsystems for a completely integrated proteomics workflow was created. This design was partially realized in a set of chips, with which preliminary data for the electrochemical cleavage reactions was generated.

To summarize, this thesis combines different approaches to furthering microfluidic approaches to modern life science problems, ranging from complex method hyphenations and chip designs to new fabrication methods.