Biomolecule Crystallization Microarray

提出的创新是一种微机电系统（MEMS），用于自动化，动力学控制的生物分子晶体生长的晶体学。创新的核心是两个新颖的组件：一个提供nL/s流量的蠕动微型泵和一个测量这种流量的流量传感器。泵和传感器将允许以单独控制的流速将缓冲液、沉淀剂和生物分子溶液递送到10-穆尔微反应器阵列。为每个微反应器服务的三个泵将被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，因此第一阶段的光学和电子方法调查将确定第二阶段实施的适当监测技术。一个独立的阶段微反应器，由精密实验室注射泵，将通过在受控的优化条件下生长鸡蛋白溶菌酶晶体进行测试。因此，第一阶段有三个具体目标：（1）微型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，这些元件将被组装成一个原型结晶器，然后将建造一系列可同时操作的反应堆进行测试。拟议的商业应用：世界上几乎所有的大型制药公司和主要的研究型大学都为晶体学结晶大分子。这种高度迭代的专业劳动密集型过程的成功自动化和小型化每年可以节省数十亿美元。SHOT，Inc.，打算将该产品销售到公司熟悉的市场。

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.