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

SBIR第一阶段项目将通过降低生物药物的制造成本和提高其质量而造福社会，包括目前生产成本太高的药物，因为它们针对的是相对较少的患者群体。这项拟议的创新将通过提供一种连续的原位多分析物传感器来推进最先进的技术，使药物质量保证的新方法成为可能。这种多分析物传感器将首次允许生物制药公司在生产过程中对产品浓度以及其他重要培养分析物的浓度进行现场监测。该传感器阵列将具有独特的能力来测量pH、渗透压以及葡萄糖、乳酸和单抗浓度之间的时间依赖关系。这种能力为优化上游生物制药生产开辟了新的途径，上游生物制药生产消耗了商品生物药品成本的约35%。使用传感器对上游过程进行有效控制，例如提议的一种传感器，预计可将这些成本降低高达30%。此外，这项技术可以通过取代传感分子而应用于其他分析物。本项目将展示将新发现的亲和配体用于生物过程传感的可行性，从而获得第一个可用于实时监测生产过程中单抗浓度的原位生物传感器。这种生物传感器将基于一种新型的磁转换刺激响应水凝胶，该水凝胶含有针对mAbs的亲和配体。该抗体传感器将集成到现有的原位生物反应器传感器阵列中，能够监测其他关键参数：pH、渗透压、葡萄糖和乳酸。因此，建议的传感器阵列将成为推进过程分析和生物制造的有力工具。产品的可行性将通过三个目标来论证：1)合成一种新型的磁转换刺激反应水凝胶，其中含有与单抗特异结合的亲和配体。2)将目标1的水凝胶掺入适合于监测细胞培养液中与生物制造相关的浓度范围内的单抗浓度的传感器中。3)将抗体传感器集成到现有的传感器阵列中，并展示其在典型抗体制造条件下的性能。这一可适应的技术可用于多种蛋白质靶标；因此，拟议的项目代表了一种变革性的方法，将在多种应用中促进生物传感的科学知识。

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.