SBIR Phase I: Development of a Miniaturized Multiwell Plate Reader

这个小型企业创新研究(SBIR)项目的更广泛的影响/商业潜力将是缓解目前在许多细菌种类的生长测量方面的几个困难，特别是厌氧和其他挑剔的生物。这些物种中有大量是自然存在于人体中的，最近被证明在过敏、自身免疫性疾病、饮食健康、癌症、感染反应等方面发挥着关键作用。对这些物种的研究被许多人认为是现代医学的下一个前沿，特别是在目前控制传染病的方法，如传统抗生素似乎正在失去效力的情况下。然而，目前的测量技术在很大程度上与厌氧微生物必须生长的专门环境和室内不相容。因此，对测量厌氧细菌生长的更好方法的大量需求尚未得到满足；随着对该领域兴趣的增加，这种需求正在迅速增长。随着对各种人类微生物群研究的加速，以及对大容量数据需求的增长，在专门环境中进行高通量实验的能力将变得至关重要。高通量测量设备的现有市场至少有3亿美元，而且还在增长；拟议的技术将把这个市场扩展到它从未服务过的领域。这个SBIR第一阶段项目建议开发一种技术，以比目前可用的高通量设备小得多的格式测量许多细菌样本的生长。系统和计算生物学的兴起表明，对大量定量数据的需求日益增长；人体内的微生物种类繁多，需要这样一种方法。然而，这种类型的数据目前几乎不可能在厌氧和其他专门环境中收集。该项目旨在通过创建简化、小型化的硬件和先进的实时分析和控制软件，将高吞吐量增长测量技术引入这些环境。S项目的第一个目标是改进一种新的概念验证光学密度测量方法，以达到与传统技术相当的准确度和精密度，并使用细菌生长和无机液体测试进行验证。下一个目标是设计一种足够小巧和坚固的硬件机箱，以允许与最小和最繁琐的环境兼容。最后，将开发软件来管理大量并行运行的细菌实验(和设备)，而不会牺牲数据保真度或高分辨率。预计由此产生的高通量测量系统将极大地扩展研究人员表征越来越具有临床相关性的微生物的能力。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the alleviation of several current difficulties in the growth measurement of many bacterial species, especially anaerobic and other fastidious organisms. A large number of these species are naturally occurring in the human body, and they have recently been shown to play critical roles in allergies, autoimmune diseases, dietary health, cancer, infection response, and more. The study of these species is considered by many to be the next frontier of modern medicine, especially as current approaches to managing infectious diseases, such as traditional antibiotics, appear to be losing effectiveness. However, current measurement technology is largely incompatible with the specialized environments and chambers in which anaerobic organisms must be grown. There is therefore a large unmet need for better ways to measure anaerobic bacterial growth; this need is growing quickly as interest in the field increases. The ability to conduct high-throughput experiments in specialized environments will become critical as research into various human microbiomes accelerates, and demand for high-volume data grows. The existing market for high-throughput measurement devices is at least $300 million and growing; the proposed technology will expand that market to fields it has never served.This SBIR Phase I project proposes to develop technology for measuring growth of many bacterial samples in a format much smaller than currently available high-throughput devices. The rise of systems and computational biology demonstrates a growing demand for large amounts of quantitative data; the variety of microbes in the human body necessitates such an approach. However, this type of data is currently nearly impossible to collect in anaerobic and other specialized environments. This project aims to bring high-throughput growth measurement techniques to these environments by creating simplified, miniaturized hardware paired with advanced real-time analysis and control software. The project?s first objective is to refine a novel proof-of-concept optical density measurement method to achieve accuracy and precision comparable to traditional techniques, and verify using bacterial growth and inorganic liquid testing. The next goal is to design a hardware enclosure small and robust enough to allow compatibility with the smallest and most taxing environments. Finally, software will be developed to manage a high number of bacterial experiments (and devices) running in parallel without sacrificing data fidelity or high resolution. It is anticipated that the resulting high-throughput measurement system will greatly expand researchers' abilities to characterize microbes of increasing clinical relevance.