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）： 我们将开发一个原型倒鱿鱼（超导量子干扰装置），用于神经科学研究。预计信号水平将比非破坏性评估区域（> 1 pt，pt = 10/-12 tesla）弱（100-500 ftrms，ftrms，ftm，ft = 10/-15 Tesla）。因此，在第一阶段，我们确定了构建Ultasenitivesquid显微镜的可行性。我们已经表明，可以使用大约70 ftrms/vhz的噪声水平来构建具有亚毫升直径拾音器线圈的磁力计式组件，该噪声水平符合我们阶段I目标中规定的一个设计标准之一。我们还确定了蓝宝石窗口的最小厚度，该窗口将作为大气压下样品与真空中的鱿鱼传感器之间的屏障。基于这些结果，我们希望应该有可能建立一个对神经科学研究足够敏感的倒鱿鱼显微镜。在特定的目标1中，我们将构建一个具有8通道磁力仪的感觉阵列的原型，每个磁力计直径约为0.6 mm，在70 ftrms/vhz或更高的情况下，检测线圈在距离神经元和神经元细胞的200 mu/m远的距离上，均具有野外敏感性。显微镜类似于倒的光学显微镜，除了物镜被一系列超导微型磁场感应线圈所取代。在特定目标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效用。首先，将在没有任何样品的磁性屏蔽室里确定场灵敏度（以ft/vhz为单位）。一旦确定系统噪声水平在指定的水平内，它将用于测量新皮层切片产生的磁场。我们将确定切片的信号水平，并与我们的预测进行比较。观察到的值和预测值之间的协议将表明，显微镜应适用于其他应用，包括：（1）来自培养物中单个神经元和神经胶质细胞的电流，（2）抗原和磁标记的粘结效率和磁性标记的抗体（抗体）以及（3）对较小的量化量的分组量的较小量元素的元素变化。所提出的鱿鱼显微镜在学术环境和行业中都应有用，以理解难以通过电极研究，用于药物发现和研究第二理智系统的小细胞的电生理学。