SBIR Phase II: Development of an SHG Instrument, Artemis QuantTM, for measuring conformational change in real time

这个小企业创新研究（SBIR）二期项目将建立一个实时检测构象变化的仪器。构象变化是指生物分子（如蛋白质）结构的变化。对于给定的蛋白质，不同的结构变化会在生物细胞中产生不同的功能效果，例如打开或关闭生化网络。几乎所有的生物过程和所有的疾病都是由一种特殊的构象变化或缺乏构象变化介导的。因此，构象变化是一个具有巨大科学和医学重要性的课题。在这个二期项目中，将对现有的内部原型仪器在软件、机械和光学设计以及流体处理方面进行多项改进，以生产出高精度和坚固耐用的仪器。该二期项目的研究目标是创造一种可供科学家使用的仪器，这是该技术发展的一个重要里程碑。这个项目更广泛的影响和商业潜力是创造一种仪器，将大大增加科学家的工作能力。对构象变化如何起作用的基本理解，也使科学家能够发现更好的或新的治疗疾病的药物。特别是，在已知因某种突变而导致或促成疾病的所有蛋白质中，有四分之三无法用常规技术加以处理。因此，许多疾病都没有有效的药物。癌症就是这样一个例子。该仪器将使科学家能够为这些疾病找到更好的新药。因此，这项创新具有巨大的社会和科学潜力。在商业上，这个第二期项目将在创新的发展中发挥关键作用。它将使美国国家科学基金会资助的技术从目前的实验室原型转变为一种仪器，这种仪器将具有强大的、可重复的和足够全面的能力，使科学家能够独立使用它。这一重要而必要的步骤是创新商业化道路上的第一步。

This Small Business Innovation Research (SBIR) Phase II project will build a real-time detection instrument for conformational change. Conformational change is a change in the structure of a biomolecule such as a protein. For a given protein, different structural changes produce different functionals effect in a biological cell, for example turning biochemical networks on or off. Virtually all biological processes, and all diseases, are mediated by a particular conformational change or the lack of one. Conformational change is thus a topic of enormous scientific and medical importance. In this Phase II project, multiple improvements will be made to the existing in-house prototype instrument, in software, mechanical and optical design, and fluidics handling, to produce an instrument with high precision and robustness. The research objective of this Phase II project is to create an instrument that can be used by scientists, an important milestone in the development of the technology. The broader impact and commercial potential of this project is to create an instrument that will significantly increase scientists? basic understanding of how conformational changes work, and also enable scientists to discover better or new medicines for diseases. In particular, three-quarters of all proteins known to cause or contribute to disease, due to some mutation, cannot be addressed using conventional techniques. Thus, no effective medicines exist for many diseases. Cancer is one such example. The instrument will enable scientists to find better and new medicines for these diseases. Thus this innovation has great societal and scientific potential. Commercially, this Phase II project will play a critical role in the development of the innovation. It will enable to transition the technology funded by NSF from the current lab prototype to an instrument that will be robust, reproducible and comprehensive enough in its capabilities to enable scientists to use it independently. This important and necessary step is the first on the path to commercialize the innovation.