Inverted SQUID microscope for neuroscience research

用于神经科学研究的倒置 SQUID 显微镜

• 批准号: 7124178
• 负责人: DOUGLAS N PAULSON
• 金额: $ 55.43万
• 依托单位: TRISTAN TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7124178
• 关键词: bioimaging /biomedical imaging; biomagnetism measurement; biomedical equipment development; electrophysiology; evaluation /testing; glia; microscopy; molecular /cellular imaging; neocortex; neurons; neurosciences; single cell analysis; superconductivity; swine; tissue /cell culture

DESCRIPTION (provided by applicant): We will develop a prototype inverted SQUID (Superconducting Quantum Interference Device) microscope for neuroscience research. The signal levels are expected to be much weaker (100-500 ftrms, ft = 10/-15 Tesla) than signals in the area of non-destructive evaluation (> 1 pT, pT= 10/-12 Tesla) where SQUID microscopes have been used previously. Therefore, in Phase I we have determined the feasibility of constructing an ultasensitiveSQUID microscope. We have shown that a magnetometer-SQUID assembly with a submillimeter diameter pickup coil can be constructed with a noise level of about 70 fTrms/VHz that meets one of our design criteria set forth in our Phase I objectives. We have also determined the minimum thickness of the sapphire window that will serve as the barrier between the sample at atmospheric pressure and the SQUID sensors in vacuum. Based on these results, we expect that it should be possible to build an inverted SQUID microscope sufficiently sensitive for neuroscience research. In Specific Aim 1, we will construct a prototype with a 8-channel magnetometer-SQUID sensory array, each magnetometer being about 0.6 mm in diameter with a field sensitivity around 70 fTrms/VHz or better with the detection coils at a distance of 200 mu/m away from neurons and glial cells to be studied. The microscope is similar to an inverted optical microscope except the objective is replaced by an array of superconducting miniature magnetic field sensing coils. In Specific Aim 2, we will test the microscope in an experimental setting in order to evaluate its utility in neuroscience research. First, the field sensitivity (in fT/VHz) will be determined in a magnetically shielded room without any sample. Once the system noise level is determined to be within the specified level, it will be used to measure magnetic fields produced by a neocortical slice. We will determine the signal levels from the slice and compare with our predictions. Agreements between the observed and predicted values will indicate that the microscope should be useful for other applications that will include measurements of: (1) electrical currents from single neurons and glial cells in culture, (2) efficiency of bonding of antigens and magnetically tagged antibodies (immunoassay), and (3) movements and conformational changes of a small number of magnetically tagged molecules in a cell for studying signaling pathways. The proposed SQUID microscope should be useful in both academic setting and industry for understanding the electrophysiology of small cells that are difficult to study with electrodes, for drug discovery and for studying second-messenger systems.

描述(由申请人提供)： 我们将为神经科学研究开发一个倒置SQUID(超导量子干涉装置)显微镜的原型。预计信号电平(100-500ftrms，ft=10/-15特斯拉)比以前使用过鱿鱼显微镜的无损评估领域的信号(&gt；1pt，PT=10/-12特斯拉)弱得多。因此，在第一阶段，我们已经确定了构建超灵敏SQUID显微镜的可行性。我们已经证明，带有亚毫米直径拾取线圈的磁强计-SQUID组件可以构建为噪声水平约为70fTrms/VHz，这符合我们在第一阶段目标中提出的设计标准之一。我们还确定了蓝宝石窗口的最小厚度，它将在常压下作为样品和真空中的SQUID传感器之间的屏障。基于这些结果，我们预计有可能建造一种足够灵敏的倒置鱿鱼显微镜，用于神经科学研究。在具体目标1中，我们将构建一个8通道磁强计-SQUID传感器阵列的原型，每个磁强计直径约0.6 mm，场灵敏度约为70fTrms/VHz或更好，探测线圈距离被研究的神经元和神经胶质细胞200 mU/m。该显微镜类似于倒置光学显微镜，只是物镜被超导微型磁场传感线圈阵列所取代。在具体目标2中，我们将在实验环境中测试显微镜，以评估其在神经科学研究中的用途。首先，场灵敏度(以FT/VHZ为单位)将在没有任何样品的磁屏蔽室中进行测定。一旦系统噪声水平被确定在指定水平内，它将被用来测量由新皮质切片产生的磁场。我们将根据切片确定信号电平，并与我们的预测进行比较。观察值和预测值之间的一致性将表明该显微镜将用于其他应用，包括测量：(1)培养中单个神经元和神经胶质细胞的电流，(2)抗原和磁性标记抗体的结合效率(免疫分析)，以及(3)用于研究信号通路的细胞中少量磁性标记分子的运动和构象变化。提出的鱿鱼显微镜应该在学术和工业上都有用，可以用来理解难以用电极研究的小细胞的电生理学，用于药物发现和研究第二信使系统。