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制药的生产成本和提高其质量来造福社会，包括目前由于针对相对较小的患者群体而生产成本过高的药物。所提出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，从而实现药物质量保证的新方法。这种多分析物传感器将允许生物制药公司，第一次，监测浓度的产品原位，因为它是沿着的浓度，其他重要的文化分析物。传感器阵列将具有测量pH、渗透压摩尔浓度和葡萄糖、乳酸盐和单克隆抗体浓度之间的时间依赖性相关性的独特能力。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。使用传感器对上游过程进行有效控制，预计可将这些成本降低30%。此外，该技术可以通过替换传感分子来针对其他分析物。因此，所提出的技术可以被用作生物制药制造或在医疗诊断，食品加工，和水quality.This项目的传感平台将证明适应新发现的亲和配体的生物过程sensing的可行性，从而获得第一个原位生物传感器，可用于监测浓度的单克隆抗体（mAb）在制造过程中在真实的时间。这种生物传感器将基于一种新的磁转导刺激响应水凝胶含有亲和配体的目标单克隆抗体。该抗体传感器将被集成到现有的原位生物反应器传感器阵列中，该传感器阵列能够监测其他关键参数：pH值、渗透压摩尔浓度、葡萄糖和乳酸。因此，所提出的传感器阵列将是推进过程分析和生物制造的有力工具。将通过三个目标证明产品可行性：1）合成含有特异性结合mAb的亲和配体的新型磁转导刺激响应性水凝胶。2)将目标1的水凝胶并入传感器中，所述传感器适于在与生物制造相关的浓度范围内监测细胞培养基中mAb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证明其性能。这种适应性强的技术可以用于许多蛋白质靶点;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.