STTR Phase I: Development of a Novel Microfluidic Technology for Discovery of Affinity Binders

这个小型企业技术转让(STTR)第一阶段项目将展示开发一种新的亲和结合试剂筛选技术的潜力。人工合成的亲和结合试剂可以改进免疫球蛋白抗体。例如，合成亲和结合试剂比基于免疫球蛋白的抗体更小、更稳定、开发成本更低、更容易溶解。此外，人工合成的亲和结合试剂可以在体外产生(不需要脊椎动物的研究)。典型的筛选技术需要固定一个纯化的抗原靶标(展示成分)，并将亲和力结合基因和表型物理连接起来。这些要求可能会限制屏幕的有效性。相反，该项目将开发一种新的专利技术，使用微流控体外分隔法和均一化验来筛选溶液中的亲和力结合物。这项研究将产生一个系统，可以在相对较短的时间内发现数十到数百个具有标记、鉴定、捕获、稳定、结晶和量化特定生物分子的真正实用的亲和结合剂。如果该项目成功，将成为用于生命科学研究、诊断和生物制药应用的新的亲和结合试剂。多年来，研究性抗体一直主导着生命科学研究市场(全球销售额约为16亿美元)，包括免疫分析(例如，ELISA)、免疫组织化学、蛋白质印迹分析和侧向流动分析等应用。然而，免疫球蛋白的产生和纯化是具有挑战性和耗时的，因为它们需要动物宿主。大多数亲和结合试剂高度稳定(可能在室温下储存)、均匀、特异和可重复性。此外，这些亲和试剂将用于可逆地捕获天然生物分子或生物分子复合体，捕获天然蛋白质用于质谱免疫分析，以及作为伴侣用于确定蛋白质的晶体结构。这些亲和结合剂将成为体外诊断(IVD)免疫分析(全球市场价值100亿美元)、治疗性药物监测和医疗设备中多路免疫分析的非常重要的组成部分。亲和结合剂最突出和最有利可图的市场将是生物制药(全球抗体市场价值500亿美元)。对单抗的投资已经产生了5种轰动一时的药物和数十种其他有价值的疗法。对合成亲和粘合剂的投资将扩大这一潜力。

This Small Business Technical Transfer (STTR) Phase I project will demonstrate the potential for developing a novel affinity binding reagent screening technology. Synthetic affinity binding reagents can improve on immunoglobulin-based antibodies. For example, synthetic affinity binding reagents are much smaller, far more stable, less costly to develop, and more soluble than immunoglobulin-based antibodies. Moreover, synthetic affinity binding reagents can be created in vitro (no vertebrate animal research is required). Typical screening technologies require immobilizing a purified antigen target (the display component), and physically connecting the affinity binder genotype and phenotype. These requirements can limit the effectiveness of the screen. In contrast, this project will develop a novel proprietary technology that screens for affinity binders in solution using microfluidic in vitro compartmentalization and a homogeneous assay. The research will result a system that can discover, within a relatively short time, tens to hundreds of affinity binders that have genuine utility to label, identify, capture, stabilize, crystallize, and quantify specific biomolecules.The broader impact/commercial potential of this project, if successful, will be new affinity binding reagents for life science research, diagnostics, and biopharmaceutical applications. Research antibodies have dominated the Life Sciences Research market for many years (approximately $1.6 billion in sales worldwide) and include applications such as immunoassays (e.g., ELISA), immunohistochemistry, western blot analysis, and lateral flow assays. However, immunoglobulins are challenging and time-consuming to create and purify, because they require animal hosts. Most affinity binding reagents are highly stable (possibly room temperature storage), uniform, specific, and reproducible. In addition, these affinity reagents will be useful for reversibly capturing native biomolecules or biomolecular complexes, capturing native proteins for mass spectrometric immunoassays, and as chaperones for determining protein crystal structures. These affinity binders will become a very important component of In Vitro Diagnostic (IVD) immunoassays ($10 billion worldwide market), therapeutic drug monitoring, and multiplexed immunoassays in point-of-care devices. The most prominent and profitable market for the affinity binders will be biopharmaceuticals ($50 billion antibody worldwide market). Investment in monoclonal antibodies has resulted in 5 blockbuster and dozens of other valuable therapeutics. Investment in synthetic affinity binders will expand this potential.