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.

这个第二阶段项目将开发一个通用的磁显微镜，并评估其在生物医学领域的应用。 以理工科为重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仪（SQUID）。加州大学滨江分校 (UCR)开发了一种新的高Tc SQUID制造技术，其结噪声可与 低Tc SQUIDS他们的方法使用聚焦的氦离子束，使约瑟夫森结与0.5纳米 精密度，从而产生可靠的，可重复的SQUID，产量高。在第一阶段，我们设计了三个 基于SQUID的磁力计。我们发现直接注入式磁力计会产生结噪声 6 µΦo/μ Hz，与低Tc SQUID噪声相当。我们把最好的一个安装在一个窗户下面， 在倒置显微镜中的显微镜载物台，并确定其在13 oK的场灵敏度为1 pT/kHz， 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回路和与拾取回路的耦合效率。UCR将建造 1x 3 SQUID芯片并在第1年交付给Tristan。特里斯坦，同时，将设计和建造一个倒置的 SQUID显微镜（iSM）基于他们以前的iSM。它将配备一个向上的荧光灯 上面的显微镜和用于刺激器和侧面的记录电极的显微操纵器。中的窗口 显微镜载物台内部将蚀刻有微通道，以实现样品之间的10-25 µm距离， SQUID阵列用于单个纳米颗粒和神经元检测。这种非常短的间隙是可能的，因为 SQUID是高Tc超导体，因此它们在> 10 oK下工作。他们将安装两个测试SQUID 将芯片放入2x 3阵列中并评估其灵敏度。一旦构建了可工作的iSM，它将被运送到 波士顿，以评估其在生物医学科学的效用，由年初2。iSM发货后，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著降低，波士顿 将把iSM运回特里斯坦，特里斯坦将用改进的SQUID芯片测试iSM。特里斯坦将运送 将改进后的iSM送回波士顿继续评估。在目标2中，Moment的Okada博士和 波士顿大学（BU）将在第一年使用一个孤立的小龙虾巨大轴突来开发磁共振成像的方法。 单个神经元的场检测。浸大的文博士将从胎鼠培养海马神经元。 在第二年，Okada和Lin博士将评估iSM用于测量单个神经元的细胞内电流。在 目标3，冈田博士和马萨诸塞州总医院Martinos中心的Medarova博士将建造 纳米颗粒和与抗生物素蛋白和生物素缀合的荧光染料。他们将利用磁性纳米粒子 AC方法，并测试iSM是否可以检测单个复合物。这将作为概念验证， 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 进行比较研究。第二阶段可交付成果----国际战略管理、业绩报告、出版物。