High Precision Bioassay Using Robotics and Statistics

描述(由申请人提供)：摘要细胞培养生物分析通常是费力和不准确的，即使在做出了实质性的开发努力之后。这些生物检测方法在生物技术行业中被广泛用于检测正在开发和批量释放的蛋白质或疫苗产品。不精确的分析和缓慢的分析开发会导致产品开发缓慢。细胞培养生物测定中的常见做法忽视了统计和监管指导，未能利用适当的随机化，也没有考虑群体效应(即，由多通道吸管引起的)。此外，缺乏对检测中的位置效应的关注，再加上对检测数据的简单分析，损害了细胞培养生物检测的精确度和效率。Lansky Consulting LLC将开发一种标准化的方法，使用实验室机器人进行细胞培养生物分析，然后进行现代统计分析。这一组合将解决随机化、位置效应、连续稀释、分组稀释和分析响应中的多个变异源的需要。本提案中描述的工作将展示与以下相关的性能收益：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测定方法方面的进展。现代生物测定方法组合的精密度提高将被证明将样品复制的需要减少了一个数量级或更多。将使用模拟数据和生物检测的长期实验室实验。这些新方法的好处包括较低的检测成本，快速应用于新的检测系统，以及易于获得设计、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，生物技术行业以及非营利性研究人员将广泛获得这种水平的检测性能。项目摘要叙述性生物测定是药物、蛋白质和疫苗产品的开发和批量释放的关键测量系统。方便地获得高性能生物检测将使生物技术产品的开发更快、更知情。改进的生物检测技术将更快地将独特的、重要的蛋白质和疫苗产品推向市场，以满足紧迫的医疗需求。

DESCRIPTION (provided by applicant): 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. Project Summary Narrative Bioassays are critical measurement systems for both development and lot release of pharmaceutical protein and vaccine products. Easy access to high performance bioassays will enable faster and better informed development of biotechnology products. Improved bioassay technology will bring unique, important protein and vaccine products to market more quickly to address pressing medical needs.