High-resolution micro-magnetometer based on novel nano-junction oxide SQUIDs

基于新型纳米结氧化物SQUID的高分辨率微磁力计

• 批准号: 9789871
• 负责人: DOUGLAS N PAULSON
• 金额: $ 49.73万
• 依托单位: TRISTAN TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789871
• 关键词: Area; Astacoidea; Avidin; Axon; Back; Biotin; Boston; Cells; Characteristics; Collaborations; Comparative Study; Complex; Coupling; Detection; Dimensions; Electrodes; Evaluation; Fluorescent Dyes; Future; General Hospitals; German population; Helium; Hippocampus (Brain); In Vitro; Injections; Ions; Liquid substance; Magnetism; Massachusetts; Measurement; Measures; Methods; Microscope; Molecular; Neurons; Neurosciences; Noise; Optics; Oxides; Performance; Phase; Physiologic pulse; Publications; Radial; Radiation; Rattus; Reporting; Reproducibility; Resolution; Sampling; Science; Shipping; Ships; Side; Signal Transduction; Small Business Innovation Research Grant; Surface; Techniques; Technology; Temperature; Testing; Transition Temperature; Tube; United States National Institutes of Health; Universities; Work; base; commercialization; comparative; design; design and construction; detector; fetal; flexibility; fluorescence microscope; improved; instrument; magnetic field; man; micromanipulator; nano; nanoparticle; novel; operation; phase 1 designs; sensor; single molecule; superconducting quantum interference device

This Phase II project will develop a general purpose magnetic microscope and evaluate its utility in biomedical sciences. The microscope will detect the magnetic field using high-transition temperature (high-Tc) sensors based on the superconducting quantum interference device (SQUID) developed during the Phase I. UC Riverside (UCR) has developed a novel high-Tc SQUID fabrication technique that gives a junction noise comparable to that of low-Tc SQUIDs. Their approach uses a focused helium ion beam to make the Josephson junction with 0.5 nm precision, resulting in reliable, reproducible SQUIDs with high yields. During Phase I we have designed three magnetometers based on this SQUID. We found the direct injection magnetometer to produce a junction noise of 6 µΦo/√Hz comparable with a low-Tc SQUID noise. We mounted the best one just below the window of a microscope stage in an inverted microscope and determined its field sensitivity at 13oK to be 1 pT/√Hz for an effective detector area of 62 µm radius. In Aim 1, UCR will improve the noise level further by optimizing the dimensions of the junction, the SQUID loop and the coupling efficiency with the pickup loop. UCR will construct 1x3 SQUID chips and deliver them to Tristan in year 1. Tristan, meanwhile, will design and construct an inverted SQUID microscope (iSM) based on their previous iSM. It will be equipped with an up-right fluorescent microscope above and micromanipulators for stimulator and recording electrodes on the sides. The window in the microscope stage will have a micro-channel etched inside to achieve a distance of 10-25 µm between a sample and the SQUID array for single nanoparticle and neuron detection. This very short gap is possible because the SQUIDs are high-Tc superconductors and thus they operate at >10oK. They will mount two of the test SQUID chips into a 2x3 array and evaluate their sensitivities. Once a working iSM is constructed, it will be shipped to Boston for evaluating its utility in biomedical sciences by the beginning of year 2. After shipping the iSM, UCR will continue to improve their SQUID chips. Once they achieve a significant reduction in detector noise, Boston will ship the iSM back to Tristan and Tristan will test the iSM with the improved SQUID chips. Tristan will ship back the improved iSM to Boston for continuing the evaluation. In Aim 2, Dr. Okada of Moment and Dr. Lin of Boston University (BU) will use an isolated crayfish giant axon during year 1 to develop the method for magnetic field detection from single neurons. Dr. Man of BU will develop cultured hippocampal neurons from fetal rats. In year 2, Drs. Okada and Lin will evaluate the iSM for measuring intracellular currents from single neurons. In Aim 3, Dr. Okada and Dr. Medarova of the Martinos Center at Massachusetts General Hospital will construct nanoparticles and fluorescent dye conjugated with avidin and biotin. They will magnetize the nanoparticles using an AC method and test whether the iSM can detect single complexes. This will serve as the proof of concept for future applications. The fluorescent signals from the same complex will be measured with the optical microscope for comparative studies. Phase II deliverables – the iSM, a performance report, publications.

该二期项目将开发通用磁力显微镜并评估其在生物医学中的实用性 科学。显微镜将使用高转变温度（高 Tc）传感器检测磁场 基于第一阶段开发的超导量子干涉装置（SQUID）。加州大学河滨分校 (UCR) 开发了一种新型高温 SQUID 制造技术，其结噪声可与 低 Tc SQUID。他们的方法使用聚焦氦离子束来制造 0.5 nm 的约瑟夫森结 精度，从而获得可靠、可重复的 SQUID，且产量高。在第一阶段我们设计了三个 基于该 SQUID 的磁力计。我们发现直接注入磁力计会产生结噪声 6 µΦo/√Hz 与低 Tc SQUID 噪声相当。我们把最好的一个安装在窗户下面 倒置显微镜中的显微镜载物台，并确定其在 13oK 时的场灵敏度为 1 pT/√Hz 有效探测器区域半径为 62 µm。在目标 1 中，UCR 将通过优化 结的尺寸、SQUID 环路以及拾波环路的耦合效率。 UCR将建设 1x3 SQUID 芯片，并在第一年将它们交付给 Tristan。同时，Tristan 将设计和建造一个倒置的 SQUID 显微镜 (iSM) 基于他们之前的 iSM。它将配备一个直立式荧光灯 上面是显微镜，侧面是用于刺激器和记录电极的显微操纵器。窗户在 显微镜载物台内部蚀刻有微通道，以实现样品之间 10-25 µm 的距离 以及用于单个纳米颗粒和神经元检测的 SQUID 阵列。这种非常短的间隙是可能的，因为 SQUID 是高温超导体，因此它们的工作温度 >10oK。他们将安装两个测试SQUID 将芯片放入 2x3 阵列并评估其灵敏度。一旦构建了可用的 iSM，它将被运送到 波士顿在第二年年初评估了其在生物医学科学中的效用。在交付 iSM 后，UCR 将继续改进他们的SQUID芯片。一旦他们实现了探测器噪音的显着降低，波士顿 将把 iSM 运回 Tristan，Tristan 将使用改进的 SQUID 芯片测试 iSM。特里斯坦将发货 将改进后的 iSM 返回波士顿继续评估。在目标 2 中，Moment 的 Okada 博士和 波士顿大学 (BU) 将在第一年使用孤立的小龙虾巨轴突来开发磁性方法 来自单个神经元的场检测。波士顿大学的曼博士将从胎鼠身上培育出海马神经元。 第二年，博士。 Okada 和 Lin 将评估 iSM 用于测量单个神经元的细胞内电流。在 目标 3，马萨诸塞州总医院 Martinos 中心的 Okada 博士和 Medarova 博士将建造 纳米颗粒和与亲和素和生物素缀合的荧光染料。他们将使用磁化纳米粒子 AC 方法并测试 iSM 是否可以检测单个复合物。这将作为概念证明 未来的应用。来自同一复合物的荧光信号将用光学显微镜测量 用于比较研究。第二阶段可交付成果——iSM、绩效报告、出版物。