High Precision Bioassay Using Robotics and Statistics

项目摘要 摘要 细胞培养生物分析通常是费力和不准确的，即使在 发展努力。这些生物检测方法在生物技术行业中被广泛使用 测量正在开发和批量发布的蛋白质或疫苗产品。不精确 化验和缓慢的化验开发会导致产品开发缓慢。普普通通 细胞培养生物测定的实践忽视了统计和监管指导，因为没有 利用适当的随机化并不考虑群体影响(即 多通道吸量管)。此外，对化验中的位置效应缺乏关注， 结合对化验数据的简化分析，折衷了精确度和 细胞培养生物测定的效率。 Lansky Consulting LLC将开发一种标准化的细胞培养生物分析方法 使用实验室机器人，然后进行现代统计分析。这一组合将 满足随机化、位置效应、连续稀释、分组稀释和 化验反应的多源变异。本提案中描述的工作将 展示与以下各项相关的性能提升： 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分裂或条带模型，以及 3)在实施这一现代标准化生物检测方法方面取得的进展。 从现代生物检测方法组合而来的精密度收益将是 显示为将对样品复制的需要减少了一个数量级或更多。两者都有 将使用模拟数据和生物检测的长期实验室实验。好处是 这些新方法包括较低的检测成本，快速应用于新的检测 系统，并轻松获取设计、实施和分析方面的最佳实践。 最重要的是，通过建立交钥匙机器人和分析生物检测系统，这一水平 将向生物技术行业广泛提供化验性能的 对非营利性研究人员也是如此。

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.