STTR Phase II: High Brightness Fluorophores for Bioscience Applications

这个小企业技术转让（STTR）第二阶段项目的更广泛的影响/商业潜力是开发新型高亮度荧光化合物（荧光团）。这些化合物将在流式细胞术中找到应用，流式细胞术是一种激光诱导荧光技术，每秒可以分析数千个细胞。这种高效的技术对于临床诊断以及血癌、干细胞和药物开发领域的研究非常重要。在流式细胞术测试中，每个细胞结构用与特定生物标志物缀合的已知荧光团染色。因此，所有细胞结构和类型的群体可以通过分析荧光信号同时确定。不幸的是，这种分析需要经验丰富的工程师，可靠的设备和高性能的试剂。所提出的高亮度荧光团将增强设备和试剂的性能，并且使得能够检测低丰度细胞结构而无需复杂的信号处理。此外，这些荧光团将提高数据可靠性，减少研究和药物开发时间和成本。这些化合物还将简化设计并降低流式细胞仪设备的成本，这将有助于扩大市场采用。该技术的商业影响预计将是显著的，因为流式细胞术的市场规模预计到2018年将达到22亿美元。该STTR第二阶段项目旨在建立一个平台技术，用于生产可以发出各种颜色的高亮度荧光团。原则上，流式细胞术可以同时检测多达30种不同的参数和30种颜色信号。然而，由于溢出（信号重叠）和自发荧光（背景噪声）的问题，目前的技术只允许进行二至八色分析以确保准确性。这些问题可以通过复杂的信号分析来部分解决，但这种方法可能容易出现分析错误。所提出的高亮度荧光团被设计为通过增加低丰度细胞的弱信号来克服溢出。此外，这些荧光团还可以通过增加信噪比来减少或消除对自发荧光背景补偿的需要。更高的信噪比将使科学家能够在更短的时间内获得分辨率良好的数据和更准确的结论。该技术将允许检测和分选低丰度细胞，并将促进免疫学研究，癌症研究以及早期疾病检测技术的进步。这将使流式细胞仪设备能够充分发挥其可靠的多色检测潜力，从而获得更好的患者和研究结果。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase II project is the development of novel high-brightness fluorescence compounds (fluorophores). These compounds will find applications in flow cytometry, a laser-induced fluorescence technique that can analyze thousands of cells per second. This efficient technique is important for clinical diagnosis, and research in the areas of blood cancer, STEM cells, and drug development. In a flow cytometry test, each cell structure is stained with a known fluorophore that is conjugated with a specific biomarker. Thus, the population of all cell structures and types can be determined simultaneously by analyzing the fluorescence signals. Unfortunately, such analysis requires experienced engineers, reliable equipment, and high-performance reagents. The proposed high-brightness fluorophores will enhance the performance of equipment and reagents, and enable the detection of low abundant cell structures without complicated signal processing. In addition, these fluorophores will improve data reliability, reduce research and drug development time, and cost. These compounds also will simplify the design and reduce the cost of flow cytometry equipment, which will help to expand market adoption. The commercial impact of this technology is expected to be significant, as the market size for flow cytometry is expected to be $2.2 billion by 2018.This STTR Phase II project aims to establish a platform technology for the production of high-brightness fluorophores that can emit in various colors. In principle, flow cytometry could simultaneously detect up to 30 different parameters with 30 color signals. However, due to the issues of spillover (signal overlap), and auto-fluorescence (background noise), the current technology allows for just two- to eight-color analysis to ensure accuracy. These issues could be resolved in part by a complicated signal analysis, but this approach may be prone to analysis errors. The proposed high-brightness fluorophores are designed to overcome spillover by increasing the weak signals of low abundance cells. In addition, these fluorophores also may reduce or eliminate the need of autofluorescence background compensation by increasing the signal to noise ratios. A higher signal to noise ratio will enable scientists to obtain well-resolved data with more accurate conclusions within a shorter amount of time. This technology will allow the detection and sorting of low abundance cells, and will promote the progress of immunology studies, cancer research, as well as technology for early disease detection. This will enabling flow cytometry equipment to be used to its full potential for reliable multi-color detection, which will lead to better patient and research outcomes.