SBIR Phase I: In-line sensor for monitoring monoclonal antibody production based on hydrogels containing peptide aptamers

This SBIR Phase I project will benefit society by reducing the cost of manufacturing biologic pharmaceuticals and improving their quality, including pharmaceuticals that are currently too costly to manufacture because they target relatively small patient populations. The proposed innovation will advance state-of-the-art by providing a continuous in-situ multi-analyte sensor enabling novel methods of drug quality assurance. This multi-analyte sensor will allow biopharmaceutical companies, for the first time, to monitor the concentration of the product in-situ as it is being produced along with the concentrations of other important culture analytes. The sensor array will have the unique ability to measure time dependent correlations between pH, osmolality, and concentrations of glucose, lactate and monoclonal antibodies. This ability unlocks new avenues for optimizing upstream biopharmaceutical production which consumes about 35% of biologic drug cost of goods. Efficient control of upstream processes using sensors such as the one proposed is expected to reduce these costs up to 30%. Furthermore, this technology can be directed towards other analytes by replacing the sensing molecules. Thus, the proposed technology can be used as a sensing platform in biopharmaceutical manufacturing or in medical diagnostics, food processing, and water quality. This project will demonstrate the feasibility of adapting newly discovered affinity ligands for bioprocess sensing; thereby obtaining the first in-situ biosensor that can be used to monitor the concentration of monoclonal antibodies (mAbs) during manufacturing in real time. This biosensor will be based on a novel magnetically transduced stimuli-responsive hydrogel containing affinity ligands that target mAbs. This antibody sensor will be integrated into an existing in-situ bioreactor sensor array capable of monitoring other key parameters: pH, osmolality, glucose, and lactate. Thus, the proposed sensor array will be a powerful tool to advance process analytics and biomanufacturing. Product feasibility will be demonstrated via three objectives: 1) Synthesize a novel magnetically transduced stimuli-responsive hydrogel containing affinity ligands that specifically bind to mAbs. 2) Incorporate the hydrogel of objective 1 into a sensor suitable for monitoring the concentration of mAbs in cell culture media in the concentration range relevant to biomanufacturing. 3) Integrate the antibody sensor into an existing sensor array and demonstrate its performance under typical antibody manufacturing conditions. This adaptable technology can be leveraged towards a number of protein targets; thus the proposed project represents a transformative approach that will advance scientific knowledge of biosensing across a multitude of applications.