DEVELOPMENT OF AN ELECTROCHEMICAL-BASED TOOLKIT FOR IMPROVED BIOPROCESSING APPLICATIONS

Abstract

Recombinant antibody therapeutics have become an important class of biopharmaceuticals that have shown effectiveness in treating a variety of diseases such as cancer, infection, and inflammation due to their high binding affinity and specificity. Importantly, process conditions established during the development and manufacture of antibodies dramatically impacts their quality, clinical efficacy, and safety. For process monitoring and control purposes, analytical technologies that enable rapid and cost-effective assessment of therapeutics are needed as they trim development time and costs. To address this need, we developed electrochemical-based analytical technologies that will enable low volume, near real-time monitoring of product quality attributes and process parameters. First, we demonstrate the development of thiolated PEG-based sensor interfaces for the detection of antibody titer and N-linked glycosylation. The interfaces couple electrochemical techniques with molecular recognition-based elements and a novel spectroelectrochemical reporter to provide rapid assessment of titer and galactosylation. Next, we demonstrate successful integration of the sensor interfaces with a microfluidic device in order to enable rapid, low volume sampling that is amenable to on-line monitoring. Lastly, we apply a mediated electrochemical probing (MEP) approach that uses redox mediators to quantitatively characterize redox-based quality information of antibodies that have undergone reduction or oxidation events. We believe that these technologies can provide fast, quantifiable results for bioprocessing applications and offer advantages in their simplicity, rapid response, and connectivity to electronics.