BioPrism: An optical nanoparticle sorting assay

描述：光流控公司计划开发一种新的蛋白质结合分析平台，称为BioPrism。Bioprism是一种可多路、无标记、基于微珠的结合分析方法。该系统将是体外分子诊断、治疗开发和分子生物学研究的理想系统。制药业一直存在对更具成本效益的高通量分析的需求，该行业经常测试数百万种化合物，以努力找到一种有效的药物(到2017年，市场规模为199亿美元)。分子结合分析是蓬勃发展的生物标记物体外诊断领域的基础(到2014年，美国的销售额为200亿美元)。市场上有几种高度多元化的基于珠粒的平台，但这些系统需要昂贵的二次标记，并增加了分析步骤。也有成功的商业系统进行无标记蛋白质结合测量；然而，它们的多路复用能力很少或根本没有。我们建议将两个系统中最好的元素结合到生物棱镜中。生物棱镜将使用康奈尔大学埃里克森实验室开发的纳米级光学设备(光子学)，目前正由Optofluidics进行商业化。使用微流控流动池，其中注入了装载珠粒的样品，平台可以通过基于尺寸的光子分离来区分裸露的纳米棒和蛋白质结合的纳米棒。由于起始纳米棒的体积较小，蛋白包覆纳米棒的尺寸显著增加。通过从不同颜色的荧光纳米颗粒开始，其中每种颜色对应于不同的探针，该方法可以很容易地被多路复用。珠子的大小将决定分析物是否结合，而珠子的荧光表明哪个探测器捕获了目标。在这个第一阶段的项目中，我们将制造我们的BioPrism芯片，使用现成的纳米颗粒对系统进行表征，进行结合测试以检测小鼠免疫球蛋白的结合，并对设备设计进行数值模拟以优化性能。在第二阶段，我们将把重点放在化验开发和“可装运”生物棱镜系统的设计和建造上。

DESCRIPTION: Optofluidics Inc. proposes to develop a novel protein-binding assay platform called the BioPrism. The Bioprism is a multiplexable, label-free, bead-based binding assay. The system will be ideal for in vitro molecular diagnostics, therapeutic development and molecular biology research. The need for more cost-effective high throughput assays is ever present in the pharmaceutical industry, which routinely tests millions of compounds in an effort to find a single effective drug ($19.9B Market by 2017). Molecular binding assays are the basis of the booming biomarker in-vitro diagnostics field ($20B in the US by 2014). There are several highly multiplexed bead-based platforms in the market, but these systems require secondary labels which are expensive and add steps to the assay. There are also successful commercial systems that do label-free protein binding measurements; however they have very little or no multiplexing capability. We propose to combine the best elements from both systems into the BioPrism. The BioPrism will use nanoscale optical devices (photonics) developed in the Erickson Lab at Cornell University and currently being commercialized by Optofluidics. Using a microfluidic flow cell, into which a bead-laden sample is injected, the platform can distinguish between bare nanobeads and protein-bound nanobeads using size- based photonic separation. Protein coated nanobeads significantly increase in size due to the small volume of the starting nanobead. By starting with fluorescent nanoparticles of different colors, where each color corresponds to a different probe, the method can be easily multiplexed. The size of the bead will determine whether analytes have bound and the fluorescence of the bead indicates which probe captured a target. In this Phase I project, we will manufacture our BioPrism chips, characterize the system using off-the-shelf nanoparticles, carry out binding assays to detect the binding of mouse IgG and carry out numerical simulations on the device design to optimize performance. In Phase II, we will focus on assay development and the design and construction of a "shippable" BioPrism system.