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

SBIR第二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。为了加速新药的上市，制药业和联邦监管机构已经认识到，生物制造中的过程分析技术(PATS)的进步是非常必要的。该项目将通过提供连续的原位传感器来推进最先进的PAT，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细胞培养条件的浓度进行现场监测。这种能力为优化生物制药生产开辟了新的途径，生物制药生产消耗了约35%的生物药物商品成本。使用传感器对上游过程进行有效控制，例如这里提出的一种传感器，预计将使这些成本降低高达30%。此外，通过取代结合的亲和配体，该技术可用于其他分析物。因此，这项技术可以作为生物制药或医疗诊断、食品加工和水质监测的传感平台。该项目将通过开发第一个适用于生物制造的连续单抗传感器，促进生物传感、水凝胶化学和过程分析的科学知识。在开发与靶标特异结合的亲和配体方面已经取得了显著的进展，但到目前为止，主要的应用是医学治疗。该项目将开发一种生物传感器，使其适应亲和配体，特别是适配子，首次应用于生物过程监测。这将通过合成第一个含有共价连接多肽适配子的抗体反应水凝胶来实现。四个目标中的每一个都将分别侧重于水凝胶、电子学、软件和系统验证。该单抗生物传感器除了能够监测细胞培养环境中的pH、渗透压、葡萄糖和乳酸等关键参数外，还将能够监测单抗的质量和产量。这种新型水凝胶将成为第一个原位生物反应器传感器的基础，用于在生物制造过程中实时测量抗体。这一适应性技术可用于多种蛋白质靶标；因此，该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。因此，拟议的传感器阵列将成为推进过程分析和生物制造的强大工具。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.