SBIR Phase I: Development of a Rapid Biologics Characterization Device

这个SBIR一期项目将建立一个新的蛋白质分析系统的可行性，用于快速和精确地表征生物制剂-基于蛋白质的药物，如抗体和重组蛋白。生物制剂在治疗癌症、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，生物制剂是在活细胞中制造的高度复杂的分子，因此，生物制剂的开发、监管批准和商业生产需要频繁的质量测试。当前的测试方法繁琐且太慢，无法提供所需的吞吐量，需要数周才能完成分析。该项目将采用微流体技术。S能够无缝集成多个分析功能，在几分钟内完成蛋白质表征分析。该项目所产生的创新方法和研究将推动蛋白质分离科学领域的发展，并扩展微流控技术领域。该项目还将改变生物药物的开发和生产，使关键的测试变得不那么繁琐和快速，并将实现更频繁、更全面的测试。这将大大提高生产力，从而在更短的时间内以更低的成本开发出更多质量更高的药物。该项目将展示一种新型的生物定量蛋白质分析平台的概念验证，该平台结合了光学监测、毛细管等电聚焦（cIEF）和质谱（MS）。本项目提出开发一种创新的微流体装置，该装置包含一种新型光导，能够在测量蛋白质水平的同时进行电泳分离和电喷雾电离。将该光导添加到该设备中，可以实现成像cIEF和MS技术的强大集成，从而可以同时定量和确定未标记蛋白质样品的质量和电荷异质性分析。这种微流控装置将是第一个将这些分析功能集成在一个适用于生物生产环境的强大快速系统中的设备。这个项目的目标是：1)设计和测试芯片，以确定最优设计；2)确定修改芯片表面所需的壁涂层，以实现微流体电泳；3)开发试剂和分析条件，通过等电聚焦实现电泳分离，并与电喷雾传递到质谱的电离兼容。第一阶段的成功将导致第二阶段的计划，我们将开发商业化的微流体芯片和试剂盒。开发商用仪器系统，并验证系统性能符合GMP要求。

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.