A Universal Micromanipulation Robot for Crystallography

描述（由申请人提供）：过程自动化已成为所有现代晶体学设施的基本要素。机器人设备可以大量生产生物大分子晶体并快速安装，从而更有效地利用宝贵的X射线资源。随着合理药物发现和结构基因组学领域研究步伐的加快，最大限度地提高这些资源生产力的需求变得更加迫切。尽管有令人印象深刻的技术进步，严重的速率限制人工操作仍然坚持在结晶顺序。这些操作通常被称为瓶颈，迄今为止一直抵制自动化。这些瓶颈中最严重的是那些与晶体收获相关的任务：从孵化器中取出晶体所需的复杂，超精确的运动远远超过了标准工业机器人的能力。需要对浸没在具有宽范围粘度的母液中的晶体进行这些操作，这带来了额外的复杂性。一个能够有效应对这些挑战的全自动系统将为研究人员提供关键的使能技术。Square One认为，显微操作、机器视觉和自适应操作员控制方面的最新进展有望实现一个集成的机器人系统，能够整合与晶体收获相关的所有任务。正如设想的那样，这种通用微操作机器人（UMR）将拥有分辨率，准确性和灵活性，以有效地在最小晶体的微米级领域操作。然而，它还将具有执行其他基本过程任务所需的运动范围和有效载荷能力。末端效应器交换能力将允许UMR收获晶体，应用冷冻缓冲液和配体，执行微量和大量接种操作，并将样品转移到浸没在液氮中的储存盒中。Square One提出了一项应用研究计划，该计划与怀俄明州大学在STTR计划下合作进行，该计划将演示UMR工作单元的功能，并建立其在没有用户干预的情况下运行的能力。Square One打算在第二阶段开发工作中建立在第一阶段成功的基础上。我们的目标是生产一个完全实现的自主版本的UMR，有效地解决了晶体学用户社区的需求，并为商业生产做好准备。 公共卫生相关性：结构引导的药物发现在治疗药物的开发中发挥着越来越重要的作用。高通量，自主机器人收获脆弱的蛋白质药物靶晶体将解决蛋白质晶体学过程中的最后一个主要瓶颈。克服这一瓶颈将大大简化目标结构的表征，并直接有助于对抗主要的人类疾病。

DESCRIPTION (provided by applicant): Process automation has become an essential element of all modern crystallography facilities. Robotic equipment allows crystals of biological macromolecules to be produced in greater numbers and rapidly mounted thus resulting in more efficient utilization of valuable X-ray resources. The need to maximize the productivity of these resources becomes more acute with the accelerating pace of research in the fields of rational drug discovery and structural genomics. Despite impressive technological progress, serious rate-limiting manual operations still persist in the crystallization sequence. These operations, commonly referred to as }bottlenecks}, have thus far resisted automation. The most serious of these bottlenecks are those tasks associated with crystal harvesting: the complex, ultra-precise motions required to retrieve a crystal from its incubation well exceed the capabilities of standard industrial robotics. The need to perform these manipulations on crystals submerged in mother liquors with a wide range of viscosities presents additional complications. A fully automated system capable of effectively addressing these challenges would provide researchers with a critical enabling technology. The Square One believes that recent advances in micromanipulation, machine vision and adaptive operator control now hold the promise for an integrated robotic system capable of consolidating all of the tasks associated with crystal harvesting. As envisioned, this Universal Micromanipulation Robot (UMR) will possess the resolution, accuracy and dexterity to effectively operate in the micron-scale realm of the smallest crystals. However, it will also have the range of motion and payload capacity needed to perform other essential process tasks. An end-effector exchange capability will allow the UMR to harvest crystals, apply cryobuffers and ligands, execute both micro- and macro-seeding operations and transfer samples to storage cassettes submerged in liquid nitrogen. Square One proposes an applied research program, conducted in cooperation with the University of Wyoming under the STTR program, which will demonstrate the functionality of a UMR work cell and establish its ability to operate without user intervention. Square One intends to build upon its Phase I success during the Phase II development effort. The goal is to produce a fully-realize autonomous version of the UMR that effectively addresses the needs of the crystallography user community and is ready for commercial production. PUBLIC HEALTH RELEVANCE: Structure guided drug discovery plays an increasingly important role in the development of therapeutic agents. High-throughput, autonomous robotic harvesting of fragile protein drug target crystal will address the last major bottleneck in the protein crystallography process. Overcoming this bottleneck will greatly streamline the characterization of target structures and contribute directly to the fight against major human diseases.