DESCRIPTION: The vast majority of biopharmaceuticals in the market today are monoclonal antibodies and their efficacy relies on the antibody’s ability to bind to antigens including infectious agents, cancer receptors, etc. These antibody drugs are synthesized by first, genetically engineering mammalian (Chinese hamster ovary, CHO) cells and then, cultivating these cells in large bioreactors. The production process and manufacturing operations have profound influence on the yield of antibody and its quality. Process variables such as pH, dissolved oxygen level, and nutrient levels in the reactor fluids can lead to highly productive living cells producing high quality products or the opposite, the generation of low yielding cells that produce damaged antibodies. Also, the secreted antibody can be oxidized in the reactor or even reduced in the purification train. This project addresses the need for rapid, scalable, and informative analytical measurements that report on the processing conditions in these reactors and the quality of the antibody. The method, “mediated electrochemical probing (MEP)” was pioneered by our groups (Bentley and Payne) over the last five years and there is widespread interest within the biomanufacturing industry for its use. We have built a robust sensor and gained new insight into a variety of samples, including those of relevance to the FDA: amino acids, cell culture media, and cells. MEP enables rapid, low cost, electrochemical measurement of raw materials, cell growth, and product formation. The data obtained is rich and informative. We will use MEP to interrogate CHO cell cultures as well as antibody product (oxidized and reduced) linking measurement of product quality to cell growth and productivity.
IDEAL CANDIDATES: Medicine, pharmacy students. Participating students will be trained in techniques of cell culture, microelectronics, microfluidics, molecular biology (RNA/DNA purification/characterization, PCR, etc.) and microscopy.
PROJECT LEAD/PRINCIPAL INVESTIGATOR: William Bentley, PhD, Distinguished Chair of Engineering and Director, Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park