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

SBIR二期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，包括目前生产成本过高的药物，因为它们针对的患者群体相对较少。为了加速新发现药物的可用性，制药行业和联邦监管机构已经确定了对生物制造过程分析技术（PAT）进步的巨大需求。该项目将通过提供一种连续的原位传感器来推进最先进的PAT，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，以监测浓度的产品在原位，因为它是沿着的浓度，其他重要的细胞培养条件。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%的生物药物成本。使用传感器（如本文提出的传感器）对上游过程进行有效控制，预计可将这些成本降低高达30%。此外，该技术可以通过替换结合的亲和配体而针对其他分析物。因此，该技术可作为传感平台应用于生物制药或医疗诊断、食品加工和水质监测。该项目将通过开发第一个适用于生物制造的连续单克隆抗体（mAb）传感器，推进生物传感、水凝胶化学和过程分析的科学知识。在开发特异性结合靶点的亲和配体方面已经取得了显着的进展，但迄今为止主要的应用是医学治疗。本计画将开发一种以亲和配体，特别是适体为基础的生物感测器，首次应用于生物过程的监测。这将通过合成含有共价连接的肽适体的第一抗体响应性水凝胶来实现。四个目标中的每一个都将分别侧重于水凝胶、电子、软件和系统验证。mAb生物传感器将能够监测mAb的质量和产量，除了关键参数：pH值，渗透压，葡萄糖和乳酸在细胞培养环境中。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，用于生物制造过程中的实时抗体测量。这种适应性强的技术可以用于许多蛋白质靶点;因此，该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。因此，拟议的传感器阵列将是一个强大的工具，以推进过程分析和生物制造。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.