SBIR Phase II: Imaging Flow Cytometer for High-Throughput High-Content Screening

这个小型企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力将是开发一种成像流式细胞仪，以实现药物发现和生物技术行业生物细胞的高通量，精确分析。该项目的目标是提供与其他高含量细胞分析技术相比数量级的吞吐量改进，这将最终导致药物发现效率的提高。高通量成像流式细胞仪是制药和生物技术行业以及流式细胞术核心设施的理想解决方案，因为需要更高通量的细胞分析。除了药物发现，这种流式细胞仪的成像能力将使研究人员能够以比目前更高的精度进行稀有细胞检测，并最终使用成像流式细胞术进行体外血液学和肿瘤学诊断。最后，高通量流式细胞仪与一个数量级更大的吞吐量将大大减少研究人员花在流式细胞仪的核心设施的时间，最终使生物医学研究的生产力普遍提高。这个SBIR第二阶段项目提出，通过引入更高的吞吐量，高内容筛选（HCS）仪器，以提高药物发现的效率。HCS通过测量单个细胞的多个参数（通常使用成像）来研究治疗化合物的作用效果和相关机制。虽然HCS在发现新药方面非常有效，但不幸的是，它具有显著的通量限制。也就是说，HCS需要在单细胞水平与群体水平上收集数据。通常，低通量读出技术，如流式细胞术和荧光成像，用于收集这些数据。该项目旨在通过引入能够以传统高通量筛选的速度进行亚细胞成像的高通量成像流式细胞仪来缓解药物发现中与成像相关的速度限制。该项目利用了基于频域多路复用的高速荧光成像模式，该模式在第一阶段开发和演示，以提供市场领先的成像性能。在第二阶段结束时，将该技术扩展为完整的流式细胞仪，目标是为执行HCS的研究人员以及一般生物医学研究社区准备一台3激光，10色成像流式细胞仪。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to develop an imaging flow cytometer to enable high-throughput, precision analysis of biological cells for the drug discovery and biotechnology industries. The goal for this project is to provide order-of-magnitude throughput improvements versus other high content cell analysis technologies, which will ultimately lead to an increase in the efficiency of drug discovery. A high throughput imaging flow cytometer is an ideal solution for the pharmaceutical and biotechnology industries, as well as flow cytometry core facilities, because of the demand for higher throughput cellular analysis. In addition to drug discovery, the imaging capability of this flow cytometer will enable researchers to perform rare cell detection with higher precision than is currently available, and ultimately, in vitro hematology and oncology diagnostics using imaging flow cytometry. Finally, a high throughput flow cytometer with an order of magnitude greater throughput will dramatically reduce the time researchers spend in flow cytometry core facilities, ultimately enabling a general increase in biomedical research productivity.This SBIR Phase II project proposes to improve the efficiency of drug discovery by introducing a higher throughput, high content screening (HCS) instrument. HCS investigates the effects and associated mechanisms of action of therapeutic compounds by measuring multiple parameters from individual cells, typically using imaging. Although HCS has been highly effective in discovery new drugs, it, unfortunately, has significant throughput limitations. Namely, HCS requires data to be collected at the single cell level versus the population level. Typically, low-throughput readout techniques, such as flow cytometry and fluorescence imaging, are used to collect this data. This project aims to alleviate the speed limitations associated with imaging in drug discovery by introducing a high-throughput imaging flow cytometer capable of performing sub-cellular imaging at the speeds of traditional high throughput screening. The project leverages a high-speed fluorescence imaging modality based on frequency domain multiplexing, which was developed and demonstrated in Phase I, to provide market-leading imaging performance. Expanding this technology into a full flow cytometer by the end of Phase II, the goal is to have a 3-laser, 10-color imaging flow cytometer ready for researchers performing HCS as well as the general biomedical research community.