Inverted SQUID microscope for neuroscience research

用于神经科学研究的倒置 SQUID 显微镜

• 批准号: 6694477
• 负责人: DOUGLAS N PAULSON
• 金额: $ 9.82万
• 依托单位: TRISTAN TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694477
• 关键词: bioengineering /biomedical engineering; bioimaging /biomedical imaging; biomagnetism measurement; biomedical equipment development; microscopy; miniature biomedical equipment; neuroimaging; neurosciences; superconductivity

DESCRIPTION (provided by applicant): We propose to test the feasibility of developing an inverted SQUID (Superconducting Quantum Interference Device) microscope for neuroscience research. It is similar to an inverted optical microscope except the objective is replaced by an array of low-temperature dc SQUID-based magnetic field pickup coils (<1 mm diameter) located <50 mu/m below a ultra-thin sapphire window (<100 pm)in a microscope stage. They will be kept at superconducting temperature by liquid helium stored in a reservoir within the microscope body. We anticipate that the sensitivity will be sufficiently high for measuring magnetic fields from as few as 1-10 neurons in brain slices or tissue culture. The existing biomagnetic sensors can measure magnetic fields from hippocampal slices without averaging when neurons in the entire slice are synchronously active, but it is not sensitive enough to measure the magnetic field under normal physiological conditions without blocking inhibitory pathways. The proposed microscope will be useful for studying such activity not only from hippocampal slices, but also from other tissues such as neocortical slices. It will be also useful for estimating the distribution of intracellular currents in excitable tissues because a magnetic field distribution above a thin tissue can be uniquely converted to the current distribution in the tissue. The "current image" may provide a new means to study functions of the cortical neurons. Although still poorly explored, the microscope could be also used to study cellular activities such as phagocytosis or molecular binding (e.g. antigen-antibody binding) by measuring movements and relaxation properties of molecules tagged with magnetic particles such as magnetite or magnetic beads. Recent developments in biomagnetic instrumentation and experimental applications suggest that the construction of such a microscope is feasible. In phase I, we wilt determine (1) noise level of a single magnetic field sensor system as a function of pickup coil diameter to evaluate whether we can build a miniature pickup coil with a noise of about 50 fTHHz needed to achieve the predicted level of sensitivity and (2) minimum thickness of the sapphire window as a function of window diameter that provides sufficient protection from the atmosphere pressure since the effective sensitivity critically depends on the distance between pickup coils and the sample. Once these key features are evaluated, we will construct a multichannel system in phase II.

描述（由申请人提供）： 我们建议测试为神经科学研究开发倒鱿鱼（超导量子干扰装置）显微镜的可行性。它类似于倒置的光学显微镜，除了物镜被一系列低温直流鱿鱼基于磁场拾取线圈（直径<1 mm）<50 mu/m以下，位于显微镜阶段的超薄蓝宝石窗口（<100 pm）下方。它们将通过在显微镜体内存储在储层中的液体氦气保持在超导温度下。我们预计，灵敏度将足够高，可以在脑切片或组织培养中测量磁场的磁场高达1-10个神经元。现有的生物磁传感器可以在整个切片中的神经元同步活跃时测量海马切片中的磁场，而无需平均，但是它不够敏感，无法在正常生理条件下测量磁场而不会阻止抑制途径。所提出的显微镜将不仅可以从海马切片中研究这种活性，而且还可以从其他组织（例如新皮层切片）中研究。它对于估计可激发组织中细胞内电流的分布也将是有用的，因为薄组织上方的磁场分布可以独特地转换为组织中的电流分布。 “当前图像”可以提供一种研究皮质神经元功能的新手段。尽管探索仍然很差，但显微镜也可用于研究细胞活性，例如吞噬作用或分子结合（例如抗原 - 抗体结合），通过测量用磁铁粒子或磁珠等磁性颗粒标记的分子的运动和弛豫特性。生物磁仪和实验应用的最新发展表明，这种显微镜的构建是可行的。在第一阶段，我们枯萎确定（1）单个磁场传感器系统的噪声水平是拾取线圈直径的函数，以评估我们是否可以建立一个微型拾音器线圈，其噪声为50 fthhz所需的噪声，以达到预测的敏感性水平，并且（2）（2）sapphire窗口的最小厚度，可在窗户直径的范围内进行最小的距离，以至于有效地保护了y rimed interiaty y rystanty y right y right y ristiation interiaty y ristantial interiaty y ristiaty airser airser的距离，因为有效地保护了有效的氛围。线圈和样品。一旦评估了这些关键功能，我们将在第二阶段构建多通道系统。