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

STTR 第一阶段：开发用于发现亲和粘合剂的新型微流体技术

• 批准号: 1321536
• 负责人: William Patterson
• 金额: $ 22.5万
• 依托单位: Isthmus Biosciences
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1321536&HistoricalAwards=false
• 关键词: STTR; Phase; Development; Novel; Microfluidic

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.

这个小企业技术转让（STTR）第一阶段项目将展示开发新型亲和结合试剂筛选技术的潜力。合成的亲和结合试剂可以改善基于免疫球蛋白的抗体。例如，合成的亲和结合试剂比基于免疫球蛋白的抗体小得多、稳定得多、开发成本更低并且更可溶。此外，合成的亲和结合试剂可以在体外产生（不需要脊椎动物研究）。典型的筛选技术需要固定纯化的抗原靶标（展示组分），并物理连接亲和结合物基因型和表型。 这些要求可能会限制屏幕的有效性。 相比之下，该项目将开发一种新型专有技术，使用微流体体外区室化和均相测定来筛选溶液中的亲和结合剂。该研究将产生一个系统，可以发现，在相对较短的时间内，数十至数百个亲和结合剂，具有真正的实用性标记，识别，捕获，稳定，结晶，和量化特定的生物分子。更广泛的影响/商业潜力，这个项目，如果成功，将是新的亲和结合试剂的生命科学研究，诊断和生物制药应用。研究抗体多年来一直主导着生命科学研究市场（全球销售额约为16亿美元），包括免疫测定等应用（例如，ELISA）、免疫组织化学、蛋白质印迹分析和侧流测定。然而，免疫球蛋白的产生和纯化具有挑战性且耗时，因为它们需要动物宿主。大多数亲和结合试剂是高度稳定的（可能在室温下储存）、均匀的、特异性的和可重现的。此外，这些亲和试剂将可用于可逆捕获天然生物分子或生物分子复合物，捕获天然蛋白质用于质谱免疫测定，以及作为分子伴侣用于确定蛋白质晶体结构。这些亲和结合剂将成为体外诊断（IVD）免疫测定（全球市场100亿美元）、治疗药物监测和床旁设备中的多重免疫测定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）。对单克隆抗体的投资已经导致了5个重磅炸弹和几十个其他有价值的治疗方法。对合成亲和粘合剂的投资将扩大这一潜力。