High Precision Bioassay Using Robotics and Statistics

使用机器人和统计学进行高精度生物测定

• 批准号: 7221731
• 负责人: David Matthew Lansky
• 金额: $ 35.47万
• 依托单位: PRECISION BIOASSAY, INC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221731
• 关键词: Accounting; Address; Algorithms; Animal Experiments; Arts; Attention; Biological Assay; Biotechnology; Cells; Code; Computer software; Consult; Cultured Cells; Data; Data Analyses; Data Compromising; Data Set; Detection; Development; Dose; Dyes; Goals; Hybrids; Industry; Laboratories; Lansky Play-Performance Status; Location; Marketing; Measurement; Measures; Medical; Methods; Modeling; Numbers; Performance; Pharmacologic Substance; Property; Proteins; Randomized; Range; Rate; Relative (related person); Reporting; Research Personnel; Robot; Robotics; Sample Size; Sampling; Simulate; Software Tools; Source; System; Technology; Testing; Time; Vaccines; Variant; Work; abstracting; assay development; base; cost; culture plates; design; improved; multicore processor; neutralizing antibody; novel; prototype; research study; response; statistics

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.

描述（由申请人提供）：摘要细胞培养生物测定通常是费力和不精确的，即使在大量的开发工作。这些生物测定广泛用于生物技术行业，以测量开发中的蛋白质或疫苗产品以及批放行。不精确的测定和缓慢的测定开发有助于缓慢的产品开发。细胞培养生物测定中的常规做法由于未能利用适当的随机化和不考虑组效应（即;由多通道移液管引起）。此外，缺乏对测定内的位置效应的关注，结合对测定数据的简单化分析，损害了细胞培养物生物测定的精度和效率。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测定，然后进行现代统计分析。该组合将解决随机化、位置效应、系列稀释、分组稀释和测定响应的多个变异来源的需求。本提案中描述的工作将展示与以下方面相关的性能增益：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图模型，以及3）这种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被证明，以减少一个数量级或更多的样品复制的需要。将使用模拟数据和长期实验室生物测定实验。这些新方法的好处包括降低分析成本，快速应用于新的分析系统，以及易于获得设计，实施和分析的最佳实践。最重要的是，通过建立一个交钥匙机器人和分析生物测定系统，这种水平的测定性能将广泛提供给生物技术行业以及非营利研究人员。叙述性生物测定是药物蛋白和疫苗产品开发和批放行的关键测量系统。容易获得高性能生物测定将使生物技术产品的开发更快，更好地知情。改进的生物测定技术将使独特的、重要的蛋白质和疫苗产品更快地进入市场，以满足迫切的医疗需求。