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

This SBIR Phase II 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. In order to accelerate the availability of newly discovered drugs, the pharmaceutical industry and federal regulatory agencies have identified a great need for advances in process analytical technologies (PATs) in biomanufacturing. This project will advance state-of-the-art PAT by providing a continuous in-situ 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 cell culture conditions. This ability unlocks new avenues for optimizing biopharmaceutical production which consumes about 35% of the biologic drug cost-of-goods. Efficient control of upstream processes using sensors such as the one proposed here is expected to reduce these costs by up to 30%. Furthermore, this technology can be directed towards other analytes by replacing the bound affinity ligands. Thus, this technology can be used as a sensing platform in biopharmaceutical manufacturing or medical diagnostics, food processing, and water quality monitoring. This project will advance scientific knowledge of biosensing, hydrogel chemistry, and process analytics by developing the first continuous monoclonal antibody (mAbs) sensor suitable for biomanufacturing. Remarkable progress has been made in developing affinity ligands that specifically bind to targets, but thus far the primary application has been medical therapeutics. This project will develop a biosensor adapting affinity ligands, aptamers in particular, for the first time for application in bioprocess monitoring. This will be accomplished by synthesizing the first antibody-responsive hydrogel containing covalently attached peptide aptamers. Each of the four objectives will focus on hydrogels, electronics, software and system validation respectively. The mAb biosensor will be capable of monitoring quality and yield of mAbs besides the key parameters: pH, osmolality, glucose, and lactate in cell culture environments. This novel hydrogel will be the basis for the first in-situ bioreactor sensor for real-time antibody measurements during biomanufacturing. This adaptable technology can be leveraged towards a number of protein targets; thus, this project represents a transformative approach that will advance scientific knowledge of biosensing across a multitude of applications. Thus, the proposed sensor array will be a powerful tool to advance process analytics and biomanufacturing. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.