SBIR Phase II: Quantitative Phase Imaging for Life Sciences

这个小型企业创新研究二期项目旨在开发一种更快、更精确的光学仪器，用于研究活细胞和组织。对活细胞的研究产生了许多发现（如细菌理论、克雷布斯循环、细胞分裂），对药物发现和疾病治疗很重要。活细胞是透明的，需要在自然状态下观察很长一段时间（天、周）。为了使细胞可见并定量测量它们，目前最先进的仪器需要向细胞注射染色剂或发光荧光团。这两种方法都是侵入性的，劳动密集型的，昂贵的，对活细胞的长期观察是困难的：染色使细胞防腐，荧光团褪色很快，几个小时内就会杀死细胞。第一阶段的项目产生了一个概念验证原型，通过处理在自然状态下通过细胞传输的光来提供活细胞的定量成像。完成第二阶段的目标将把第一阶段的原型升级为商业级仪器：改进光学设计和建造外壳，开发商业级软件和自动化硬件控制，开发特定任务的软件应用程序，以解决特定的生物问题。该项目更广泛的影响/商业潜力是使生命科学家能够使用一种新的强大的仪器来研究活细胞。在第二阶段项目中开发的商业仪器的最大影响将是使研究人员能够比以前更好地进行科学研究，即更准确，更定量，更无创。该仪器带来的一系列突破可能包括：通过精确监测细胞对治疗的反应来发现新药，细胞增殖和生长的基础研究，癌症活检的微创自动诊断，以及快速准确的血液检测仪器。扩大该仪器的生产规模将创造新的就业机会，并增强美国在生物技术领域的主导地位。由于完全自动化，这些仪器也可以在训练有素的人员接触有限的地区运行，并提供远程诊断所需的数字数据，例如美国医疗服务不足的地区/人口。

This Small Business Innovation Research Phase II project proposes to develop a faster and more accurate optical instrument for studying live cells and tissues. The study of live cells has yielded numerous discoveries (e.g. germ theory, the Krebs cycle, cell division) and is important for drug discovery and disease treatment. Live cells are transparent and need to be observed for long periods of time (days, weeks) in their natural state. To make the cells visible and measure them quantitatively, current state of the art instruments require injecting the cells with staining agents or light emitting fluorophores. Both processes are invasive, labor intensive and expensive and long term observations of live cells is difficult: staining embalms the cells and the fluorophores fade quickly and kill the cells in hours. The Phase I project produced a proof-of-concept prototype that provides quantitative imaging of live cells by processing the light transmitted through the cells in their natural state. Completion of the Phase II objectives will upgrade the Phase I prototype to a commercial grade instrument: improve optical design and build a housing enclosure, develop commercial grade software and automate the hardware controls and develop task-specific software applications to solve particular biological problems. The broader impact/commercial potential of this project is to enable life scientists with a new and powerful instrument for studying live cells. The greatest impact of the commercial instrument developed in Phase II project will have is enabling researchers to do science better than before, i.e., more accurately, more quantitatively, and more noninvasively. The range of breakthroughs enabled by the instrument will likely include: novel drug discovery by accurate monitoring of cell response to treatment, fundamental studies of cell proliferation and growth, minimally invasive automatic diagnosis of cancer biopsies, and fast and accurate blood testing instruments. Scaling up the production of the instrument will create new jobs and increase the US dominance in the biotechnology area. Due to their full automation, the instruments can also operate in areas with limited access to trained personnel and provide the digital data necessary for remote diagnosis, such as Medically Underserved Areas/Populations in United States.