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

这个SBIR一期项目将通过降低生物药品的生产成本和提高其质量，包括目前生产成本过高的药品，因为它们针对的是相对较小的患者群体，从而造福社会。提议的创新将通过提供连续的原位多分析物传感器来推进最先进的技术，从而实现药物质量保证的新方法。这种多分析物传感器将首次允许生物制药公司在产品生产过程中监测产品的浓度以及其他重要培养分析物的浓度。该传感器阵列将具有独特的能力来测量pH值，渗透压和葡萄糖，乳酸和单克隆抗体浓度之间的时间依赖性相关性。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约35%的生物药品成本。利用上述传感器对上游流程进行有效控制，预计可将成本降低30%。此外，该技术可以通过替换传感分子来指导其他分析物。因此，所提出的技术可以用作生物制药制造或医疗诊断、食品加工和水质中的传感平台。该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；从而获得了第一个可用于在生产过程中实时监测单克隆抗体（mab）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导刺激反应水凝胶，该水凝胶含有靶向单克隆抗体的亲和配体。这种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，所提出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证明：1)合成一种新型的磁转导刺激反应水凝胶，该水凝胶含有特异性结合单克隆抗体的亲和配体。2)将物镜1的水凝胶掺入传感器中，用于监测细胞培养基中单克隆抗体在生物制造相关浓度范围内的浓度。3)将抗体传感器集成到现有的传感器阵列中，并在典型的抗体制造条件下演示其性能。这种适应性强的技术可以用于许多蛋白质靶标；因此，拟议的项目代表了一种变革性的方法，将在众多应用中推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.