SBIR Phase I: Development of a Rapid Biologics Characterization Device

这个SBIR第一阶段项目将建立一种新的蛋白质分析系统的可行性，用于快速和准确地鉴定生物制剂--基于蛋白质的药物，如抗体和重组蛋白质。生物制品在治疗癌症、牛皮癣等多种疾病方面取得了显著的疗效，是发展最快的药物开发领域。然而，生物制品是在活细胞中制造的高度复杂的分子，因此，生物制品的开发、监管批准和商业生产需要频繁的质量测试。目前的测试方法繁琐且速度太慢，无法提供所需的吞吐量，需要数周时间才能完成分析。该项目将利用微流控技术？S的能力，无缝集成多种分析功能，在几分钟内完成蛋白质表征分析。该项目的创新方法和研究成果将推动蛋白质分离科学领域的发展，拓展微流控技术领域。该项目还将改变生物药物的开发和制造，使关键测试变得不那么繁琐和快速，并将使更频繁、更全面的测试成为可能。这将带来显著的生产率提高，转化为以更短的时间和更低的成本开发出更多更高质量的药物。该项目将展示一种新型生物制剂定量蛋白质分析平台的概念验证，该平台结合了光学监控、毛细管等电聚焦(CIEF)和质谱分析(MS)。该项目建议开发一种创新的微流控设备，该设备结合了一种新型的光导，能够在同时进行电泳分离和电喷雾电离的同时测量蛋白质水平。将该光导添加到该设备中，可以实现成像的CIEF和MS技术的强大集成，从而能够同时定量和确定未标记蛋白质样品的质量和电荷异质性图谱。这种微流控装置将是第一个证明将这些分析功能集成到一个适用于生物生产环境的强大而快速的系统中。该项目的目标将是：1)设计和测试芯片，以确定最佳设计；2)确定修改芯片表面以实现微流控电泳所需的壁涂层，以及3)开发试剂和分析条件，以实现等电聚焦分离，并与电喷雾传输到质谱仪的电离兼容。第一阶段的成功将导致第二阶段的计划，在该计划中，我们将开发商业微流控芯片和试剂盒，开发商业仪器系统，并验证系统性能是否符合GMP标准。

This SBIR Phase I project will establish the feasibility of a new protein analysis system for rapid and precise quality characterization for biologics - protein-based drugs such as antibodies and recombinant proteins. Biologics have achieved remarkable efficacy for many diseases, e.g. cancer, psoriasis, and are the fastest growing drug development segment. However, biologics are highly complex molecules manufactured in living cells, and as a result, frequent quality testing is required for development, regulatory approval, and commercial manufacturing of biologics. Current testing approaches are cumbersome and too slow to provide the required throughput, taking weeks to complete an analysis. This project will utilize microfluidic technology?s ability to seamlessly integrate multiple analytical functions to complete a protein characterization analysis in only minutes. The innovative approaches and research resulting from this project will advance the fields of protein separation science and expand the microfluidic technology field. This project will also transform biologic drug development and manufacturing by making the critical testing less cumbersome and faster, and will enable more frequent, comprehensive testing. This will result in profound productivity gains that will translate into a greater number of higher quality drugs developed in less time and with less cost.This project will demonstrate proof-of-concept for a novel quantitative protein analysis platform for biologics that combines optically-monitored, capillary isoelectric focusing (cIEF) and mass spectrometry (MS). This project proposes to develop an innovative microfluidic device that incorporates a novel light guide, which is capable of measuring protein levels while simultaneously performing electrophoretic separation and electrospray ionization. Adding this light guide to this device enables a powerful integration of imaged cIEF and MS techniques, enabling simultaneous quantitation and determination of mass and charge heterogeneity profiling of unlabeled protein samples. This microfluidic device will be the first demonstrated integration of these analytical functions in a robust and rapid system suitable for the bioproduction environment. The goals of this project will be to: 1) design and test chips to identify the most optimal design, 2) identify wall coatings required to modify chip surfaces to enable microfluidic electrophoresis, and 3) develop reagents and assay conditions to enable electrophorectic separation by isoelectric focusing that are compatible with ionization for electrospray delivery to mass spec. Success in Phase I will lead to a Phase II program in which we will develop a commercial microfluidic chip and reagent kit, develop the commercial instrument system, and validate the system performance for GMP compliant use.