Biomolecule Crystallization Microarray

提出的创新是一种微机电系统（MEMS），用于自动，动态控制生长的生物分子晶体用于晶体学。创新的核心是两个新颖的组件：一个提供nL/s流量的蠕动微泵和一个测量这种流量的流量传感器。泵和传感器可以将缓冲液、沉淀剂和生物分子溶液输送到单独控制流量的10 μ l微反应器阵列中。为每个微反应器服务的三个泵将相互协调，以保持优化的成核条件和单独优化的晶体生长条件。主动控制需要监测成核/生长晶体，因此第一阶段对光学和电子方法的调查将为第二阶段的实施确定一种适当的监测技术。一个独立的相微反应器，由精密的实验室注射泵提供服务，将在控制优化的条件下通过生长蛋清溶菌酶晶体进行测试。因此，第一阶段有三个具体目标：(1)微泵和流量传感器的微制造和测试，(2)结晶监测方法的选择，以及(3)独立进料控制结晶微反应器的制造和测试。在第二阶段，这些元素将被组装成一个原型结晶器，然后将建造一组同时可操作的反应堆进行beta测试。建议的商业应用：几乎世界上所有的大型制药公司和主要的研究型大学都将大分子结晶用于晶体学。成功的自动化和小型化这种高度迭代，专业的劳动密集型过程可以影响每年节省估计数十亿美元。SHOT, Inc.打算将该产品销售到本公司熟悉的市场。

The proposed innovation is a microelectromechanical system (MEMS) for automated, kinetically controlled growth of biomolecule crystals for crystallography. Central to the innovation are two novel components: a peristaltic micropump that delivers nL/s flows and a flow sensor that measures such flows. Pumps and sensors will allow delivery of buffer, precipitant, and biomolecule solutions to an array of 10-muL microreactors at individually controlled flow rats. The three pumps serving each microreactor will be coordinated to maintain optimized nucleation conditions and separately optimized crystal growth conditions. Active control requires monitoring of nucleating/growing crystals, so a Phase I survey of optical and electronic methods will identify aan appropriate monitoring technology for Phase II implementation. A stand-alone Phase microreactor, served by precision laboratory syringe pumps, will be tested by growing hen egg-white lysozyme crystals under controlled optimized conditions. Thus, Phase I has three Specific Aims: (1) microfabrication and testing of the micropump and flow sensor, (2) selection of a crystallization monitoring method, and (3) fabrication and testing of a stand-alone feed-controlled crystallization microreactor. In Phase II, the elements will be assembled into a prototype crystallizer, and then an array of simultaneously operable reactors will be built for beta testing. PROPOSED COMMERCIAL APPLICATIONS: Nearly all of the world's large pharmaceutical firms and major research universities crystallize macromolecules for crystallography. Successful automation and miniaturization of this highly iterative, professional- labor-intensive process could effect annual savings estimated at billions of dollars. SHOT, Inc., intends to sell this product into a market with which the Company is familiar.