A Universal Micromanipulation Robot for Crystallography

通用晶体学显微操作机器人

• 批准号: 7651304
• 负责人: ROBERT VIOLA
• 金额: $ 59.01万
• 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 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7651304
• 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; Operative Surgical Procedures; Pattern Recognition; Phase; Play; Process; Production; Productivity; Proteins; Research; Research Personnel; Resolution; Resources; Robot; Robotics; Roentgen Rays; Role; Sampling; Small Business Technology Transfer Research; 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; meetings; nano; nanofluidic; novel; programs; prototype; public health relevance; sensory system; 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。机器人设备可以大量生产并快速安装生物大分子晶体，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。尽管技术取得了令人印象深刻的进步，但在结晶过程中仍然存在严重限制速率的手动操作。这些操作通常被称为“瓶颈”，迄今为止一直难以实现自动化。其中最严重的瓶颈是与晶体采集相关的任务：从孵化中取出晶体所需的复杂、超精确的运动远远超出了标准工业机器人的能力。对浸没在各种粘度的母液中的晶体进行这些操作的需要带来了额外的复杂性。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支持技术。 Square One 相信，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打造出一种能够整合与晶体采集相关的所有任务的集成机器人系统。正如设想的那样，这款通用微操作机器人（UMR）将拥有在最小晶体的微米级领域有效操作的分辨率、准确性和灵活性。然而，它还具有执行其他基本过程任务所需的运动范围和有效负载能力。末端执行器交换功能将使 UMR 能够收获晶体、应用冷冻缓冲液和配体、执行微观和宏观播种操作并将样品转移到浸没在液氮中的存储盒中。 Square One 提出了一项应用研究计划，该计划与怀俄明大学在 STTR 计划下合作开展，该计划将展示 UMR 工作单元的功能并建立其在无需用户干预的情况下运行的能力。 Square One 打算在第二阶段的开发工作中以第一阶段的成功为基础。目标是生产完全实现的 UMR 自主版本，有效满足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。克服这一瓶颈将极大地简化目标结构的表征，并直接为对抗人类主要疾病做出贡献。