High Precision Bioassay Using Robotics and Statistics

项目摘要 摘要 细胞培养生物测定通常是费力的并且不精确的，即使在大量的细胞培养之后也是如此。 发展努力。这些生物测定广泛用于生物技术工业， 测量蛋白质或疫苗产品的开发和批放行。不精确 测定和缓慢的测定开发导致缓慢的产品开发。共同 细胞培养生物测定的实践忽视了统计和法规指导， 利用适当的随机化，不考虑组效应（即;由于 多通道移液管）。此外，缺乏对测定中位置效应的关注， 与分析数据的简单分析相结合，损害了精确度， 细胞培养生物测定的效率。 Lansky Consulting LLC将开发细胞培养生物测定的标准化方法 使用实验室机器人，然后进行现代统计分析。这种组合将 解决随机化、位置效应、系列稀释、分组稀释的需求，以及 测定响应的多个变异来源。本提案所述工作将 展示与以下方面相关的性能提升： 1)标准化设计（包括需要机器人进行随机化的设计）， 2)用于生物测定分析的线性和非线性混合裂区或条区模型，以及 3)这一现代标准化生物测定方法的实施进展。 从现代生物测定方法的组合包的精度增益将是 显示出将样品复制的需要减少一个数量级或更多。两 将使用模拟数据和长期实验室生物测定实验。的好处 这些新方法包括降低检测成本，快速应用于新的检测 系统，以及轻松访问设计、实施和分析方面的最佳实践。 最重要的是，通过构建交钥匙机器人和分析生物测定系统， 的分析性能将广泛提供给生物技术行业， 以及非营利研究人员。

Project Summary Abstract Cell culture bioassays are often laborious and imprecise even after substantial development efforts. These bioassays are used broadly in the biotechnology industry to measure protein or vaccine products in development and for lot release. Imprecise assays and slow assay development contribute to slow product development. Common practice in cell culture bioassay ignores statistical and regulatory guidance by failing to utilize proper randomization and not accounting for group effects (i.e.; as caused by multi-channel pipettes). In addition, lack of attention to location effects within the assays, combined with simplistic analyses of assay data, compromise the precision and efficiency of cell culture bioassays. Lansky Consulting LLC will develop a standardized approach to cell culture bioassay using laboratory robots followed by modern statistical analysis. This combination will address the need for randomization, location effects, serial dilution, grouped dilution, and multiple sources of variation in assay response. The work described in this proposal will demonstrate the performance gains associated with: 1) standardized designs (including designs that require robots for randomization), 2) linear and nonlinear mixed split- or strip-plot models for bioassay analysis, and 3) advances in implementation of this modern standardized approach to bioassays. The precision gains from the combined package of modern bioassay methods will be shown to reduce the need for sample replication by an order of magnitude or more. Both simulated data and long-term lab experiments with bioassays will be used. The benefits of these new methods include lower assay costs, rapid application to new assay systems, and easy access to best practices in design, implementation, and analysis. Most importantly, by building a turnkey robotic and analysis bioassay system, this level of assay performance will be made broadly available to the biotechnology industry as well as to non-profit researchers.