Micromechanical Oscillators for Imaging Molecules by Magnetic Resonance Force Microscopy

用于磁共振力显微镜成像分子的微机械振荡器

• 批准号: 9318002
• 负责人: Joseph Garbini
• 金额: $ 50.38万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 1998-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9318002&HistoricalAwards=false
• 关键词: Micromechanical; Oscillators; Imaging; Molecules; Magnetic

9318002 Garbini A recent series of articles by Joe Garbini, John Sidles, and Gary Drobny of the University of Washington has described a new method for imaging individual molecules. The proposed imaging technology is based on a variation of the Stern- Gerlach experiment, in which the linear particle trajectories of the classic Stern-Gerlach experiment are replaced by the "folded" trajectory of a micrometer-scale mechanical oscillator. In theory, this new approach to magnetic resonance imaging combines the single-particle sensitivity of the Stern- Gerlach experiment, the nondestructive 3D imaging capability of magnetic resonance, and the subAngstrom spatial resolution of scanning probe techniques. It might therefore serve as the basis of a technology for imaging biomolecular structure. More recently, Dan Rugar and Nino Yannoni of IBM Almaden Laboratories have reported the first experimental detection of magnetic resonance by force microscope means. It is noteworthy that this first experiment achieved a room- temperature sensitivity comparable to the best available room-temperature inductive coils. The broad objective of the proposed research is to develop practical instruments for imaging individual biological molecules in situ. This imaging technology would be nondestructive, fully three-dimensional, and would achieve subAngstrom spatial resolution. Published theoretical work indicates that successful molecular imaging will require a force sensitivity of approximately 10-19 N/Hz. In comparison, the room- temperature cantilever in the UW/IBM experiment experimentally demonstrated a sensitivity of 10-15 N/Hz. One goal of the proposed research is to attain a sensitivity of 10-17N/Hz suing commercially available cantilevers. On a logarithmic scale, this represents progress half-way toward the overall goal of developing a practical molecular imaging technology. As discussed in the body of this proposal, it is reasonable to expect substantial impro vements in sensitivity from: (1) operating a t cryogenic temperatures (3-10K), instead of room temperature, (2) operating in a high vacuum, as opposed to a millitorr vacuum, (3) removing the gold metallic coating from the cantilever, (4) baking surface contaminants off the cantilever, (5) annealing the cantilever material to reduce dislocation density. A primary focus of our research is to do these experiments, which will serve to establish a reliable and experimentally validated understanding of noise mechanical oscillators. This applied knowledge base will serve as the necessary foundation for developing a practical biomolecular imaging technology. A more fundamental objective of our program is to establish a reliable and experimentally validated understanding o noise mechanisms in microscale mechanical oscillators. This applied knowledge base will serve as the necessary foundation for developing a practical biomolecular imaging technology. There reasonable scientific grounds to expect that the next generation o molecular biologist will routinely, quickly, and easily obtain images showing the full three-dimensional structure of the molecules they are studying, in situ, with all their ligands, cross-links, and glycosylation in place. This structural imaging capability, if it can be achieved, will complement and enhance the value of existing instruments for the rapid sequencing of genes and proteins, by providing a structural context for interpretation of sequence information. Our hope is that this will substantially accelerate the development of effective treatments for presently intractable disorders.

9318002 Garbini华盛顿大学的Joe Garbini、John Sidles和加里Drobny最近发表了一系列文章，描述了一种对单个分子成像的新方法。 所提出的成像技术是基于斯特恩-盖拉赫实验的变化，其中经典斯特恩-盖拉赫实验的线性粒子轨迹被微米级机械振荡器的“折叠”轨迹所取代。 理论上，这种新的磁共振成像方法结合了Stern-盖拉赫实验的单粒子灵敏度、磁共振的非破坏性3D成像能力和扫描探针技术的亚埃空间分辨率。 因此，它可以作为生物分子结构成像技术的基础。 最近，IBM Almaden实验室的Dan Rugar和Nino Yannoni报告了第一个通过力显微镜手段检测磁共振的实验。 值得注意的是，该第一实验实现了与最佳可用室温感应线圈相当的室温灵敏度。 拟议研究的广泛目标是开发用于原位成像单个生物分子的实用仪器。 这种成像技术将是非破坏性的，完全三维的，并将实现亚埃的空间分辨率。 已发表的理论工作表明，成功的分子成像将需要大约10-19 N/Hz的力灵敏度。 相比之下，UW/IBM实验中的室温悬臂梁实验证明灵敏度为10-15 N/Hz。 所提出的研究的一个目标是使用市售的杠杆获得10- 17 N/Hz的灵敏度。 在对数尺度上，这代表着朝着开发实用分子成像技术的总体目标前进了一半。 如本建议书正文所述，预期以下因素会大幅提高敏感度是合理的： (1)在低温（3- 10 K）而不是室温下操作，（2）在与毫托真空相反的高真空下操作，（3）从悬臂上去除金金属涂层，（4）烘烤悬臂上的表面污染物，（5）退火悬臂材料以降低位错密度。 我们研究的主要重点是做这些实验，这将有助于建立一个可靠的和实验验证的理解噪声机械振荡器。 这一应用知识库将作为开发实用生物分子成像技术的必要基础。 我们计划的一个更基本的目标是建立一个可靠的和实验验证的理解微尺度机械振荡器的噪声机制。 这一应用知识库将作为开发实用生物分子成像技术的必要基础。 有合理的科学依据可以预期，下一代分子生物学家将常规地、快速地、容易地获得显示他们正在研究的分子的完整三维结构的图像，包括所有的配体、交联和糖基化。 这种结构成像能力，如果能够实现，将补充和提高现有的基因和蛋白质的快速测序仪器的价值，通过提供一个结构背景的序列信息的解释。 我们希望这将大大加快目前难治性疾病的有效治疗方法的发展。