A Universal Micromanipulation Robot for Crystallography

通用晶体学显微操作机器人

• 批准号: 7481469
• 负责人: ROBERT VIOLA
• 金额: $ 57.36万
• 依托单位: SQUARE ONE SYSTEMS DESIGN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7481469
• 关键词: Acute; Address; Algorithms; Applied Research; Articular Range of Motion; Automation; Biological; Cells; Collaborations; Communities; Complex; Coupled; Crystallization; Crystallography; Development; Diffusion; Drug Delivery Systems; Elements; Equipment; Goals; Harvest; Human; Image; In Situ; Individual; Intervention; Ligands; Lighting; Liquid substance; Location; Manuals; Micromanipulation; Mothers; Motion; Nitrogen; Numbers; Operative Surgical Procedures; Pattern Recognition; Phase; Play; Process; Production; Productivity; Proteins; Public Health; Range; Range of motion exercise; Rate; Research; Research Personnel; Resolution; Resources; Robot; Robotics; Roentgen Rays; Role; Sampling; Small Business Technology Transfer Research; Standards of Weights and Measures; Structure; System; Techniques; Technology; Testing; Therapeutic Agents; Time; Universities; Viscosity; Vision; Work; Wyoming; base; design; distilled alcoholic beverage; drug discovery; fight against; human disease; improved; macromolecule; nano; nanofluidic; novel; programs; prototype; sensory system; size; structural genomics; success

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.

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。机器人设备使生物大分子的晶体数量更大并迅速安装，从而更有效地利用了有价值的X射线资源。随着理性药物发现和结构基因组学领域的研究速度加速，这些资源的生产力最大化变得更加敏锐。尽管具有令人印象深刻的技术进步，但严重的限制手动操作仍然存在于结晶序列中。这些操作通常称为}瓶颈}，到目前为止，它们已经抵抗了自动化。这些瓶颈中最严重的是与晶体收获相关的那些任务：从其孵育中检索晶体所需的复杂，超精致的运动超出了标准工业机器人技术的能力。需要对浸入具有广泛粘性的母液中的晶体进行这些操作会带来其他并发症。能够有效解决这些挑战的全自动系统将为研究人员提供重要的启用技术。正方形认为，微观流动，机器视觉和自适应操作员控制的最新进展现在有望巩固能够巩固与晶体收获相关的所有任务的集成机器人系统。如前所述，这种通用的微观流动机器人（UMR）将具有有效在最小晶体的微米级境界中运行的分辨率，准确性和灵巧性。但是，它还将具有执行其他基本过程任务所需的运动和有效负载能力范围。最终效应器交换能力将使UMR能够收获晶体，施加冷冻剂和配体，执行微种子和宏种子操作，并将样品转移到浸入液氮中的储存盒中。 Square One提出了一项应用研究计划，该计划与STTR计划下的怀俄明大学合作进行，该计划将展示UMR工作单元的功能，并确定其在没有用户干预的情况下操作的能力。第一方打算在II阶段开发工作中取得I阶段的成功。目的是生产UMR的完全实现的自主版本，该版本有效地满足了晶体学用户社区的需求，并准备好进行商业生产。 公共卫生相关性：结构指导的药物发现在治疗剂的发展中起着越来越重要的作用。脆弱蛋白药物靶晶体的高通量，自主的机器人收获将解决蛋白质晶体学过程中的最后一个主要瓶颈。克服这种瓶颈将极大地简化目标结构的特征，并直接为与主要人类疾病的斗争做出贡献。