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

这个小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力是通过引入一种用于高通量细胞荧光成像的新型仪器来提高发现新药的效率。这项创新将使制药研究人员能够以比最先进的仪器快一个数量级的速度对单个细胞进行成像，这将提高科学家进行药物筛选实验的速度。通过在这些筛选实验期间拍摄单个细胞的高分辨率图像，可以收集比使用传统高通量方法更详细的信息，从而对药物-细胞相互作用有更深入的科学理解。该仪器将通过为药物发现行业提供新型的高通量读出能力来满足不断增长的150亿美元的药物发现仪器市场。此外，对细胞进行多重多色荧光成像的能力将减少鉴定新药物化合物所需的实验数量，从而提高效率并降低药物发现的成本，最终缩短新药的上市时间。该SBIR I期项目提出开发成像流式细胞仪仪器，以提高药物发现领域的单细胞分析速度。虽然多参数单细胞表型分析提供了关于药物化合物的细胞相互作用的大量信息，但这种类型的实验读数太慢，无法在药物发现实验室中常见的大量样品上执行。通过对流动中的细胞进行并行荧光图像分析，可以加速该过程，使得每天可以在自动化实验室环境中筛选超过100，000种化合物。该项目旨在开发一种能够使用荧光进行高通量图像分析的仪器，结合流式细胞术和高速荧光显微镜领域的技术和技术，以实现这一通量目标。该项目的成功结果将产生一种能够使用多种荧光颜色对以每秒米的流速流动的细胞进行成像的仪器，具有衍射限制的空间分辨率。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to improve the efficiency of discovering new drugs by introducing a new type of instrument for fluorescent imaging of cells at high throughput. This innovation will allow pharmaceutical researchers to image individual cells at speeds more than an order of magnitude faster than the state-of-the-art instrumentation, which will improve the rate at which scientists run drug screening experiments. By taking high-resolution images of individual cells during these screening experiments, far more detailed information can be gleaned than using conventional high throughput methods, leading to a deeper scientific understanding of drug-cell interactions. This instrument will address the growing $15 billion drug discovery instrumentation market by providing a new type of high throughput readout capability for the drug discovery industry. Further, the ability to perform multiplexed multi-color fluorescent imaging of cells will reduce the number of experiments required to identify new pharmaceutical compounds, thereby improving the efficiency and reducing the cost of drug discovery, ultimately reducing the time-to-market of new drugs. This SBIR Phase I project proposes to develop an imaging flow cytometer instrument to improve the speed of single-cell analysis in the field of drug discovery. While multi-parameter single-cell phenotypic analysis provides great information about the cellular interactions of a pharmaceutical compound, this type of experimental readout is too slow to perform on the large numbers of samples common in a drug discovery laboratory. By performing parallel fluorescent image analysis of cells in flow, this process can be accelerated such that more than 100,000 compounds can be screened each day in an automated laboratory setting. This project aims to develop an instrument capable of such high throughput image analysis using fluorescence, combining techniques and technologies adapted from the fields of flow cytometry and high-speed fluorescence microscopy to accomplish this throughput goal. The successful outcome of this project will yield an instrument capable of imaging cells flowing at meter per second flow rates with diffraction-limited spatial resolution using multiple fluorescent colors.