SQUID Microscope System for Biological Immunoassay

用于生物免疫分析的 SQUID 显微镜系统

• 批准号: 12555117
• 负责人: ENPUKU Keiji
• 金额: $ 8.45万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12555117/
• 关键词: Immunoassay; Magnetic Nanoparticle; SQUID Microscope; Antigen-Antibody; Magnetic Marker; Superconductivity; フラックスダム; 補償コイル; SQUID磁気センサ; 磁気微粒子; スイッチ付きコイル; 残留磁気; 磁束ノイズ; グラディオメーター

In this project, we have developed a SQUID microscope system for the application to biological immunoassay. In this system, an antibody is labeled with the so-called magnetic marker, and the binding reaction between antigen and its antibody is detected by measuring the magnetic signal from the marker. Utilizing a highly sensitive SQUID sensor that can measure very weak magnetic signal, we can detect very small binding reaction. Since the SQUID has to be cooled to T=77 K, we developed the SQUID microscope where the distance between the SQUID and the room temperature sample can be made less than 1 mm. We also developed a new marker using the Fe_3O_4 magnetic nanopartice with diameter of 25 nm. This marker can generate magnetic signal 10 times larger than the conventional marker with diameter of 10 nm. This marker can also keep the remanent magnetic field after the marker is magnetized with a large field. Using the SQUID microscope and the new marker, we can detect the marker as small as 1 pg. We also made an immunoassay experiment. For the antigen, we used the protein called IL8. At present, we can detect the IL8 as small as 1 pg. However, we can expect to detect the IL8 less than 0.1 pg from the noise performance of the system. Since the magnetic contamination of the substrate limits the detection level at present, we have to solve this problem in order to detect the IL8 of 0.1 pg.

在这个项目中，我们开发了一个用于应用生物免疫测定的鱿鱼显微镜系统。在该系统中，用所谓的磁标记标记抗体，并通过测量标记物中的磁信号来检测抗原及其抗体之间的结合反应。利用高度敏感的鱿鱼传感器可以测量非常弱的磁信号，我们可以检测到非常小的结合反应。由于必须将鱿鱼冷却至t = 77 K，因此我们开发了鱿鱼显微镜，在该显微镜中，鱿鱼和室温样品之间的距离可以小于1 mm。我们还使用直径为25 nm的FE_3O_4磁性纳米室开发了一个新标记。该标记可以产生磁信号，比直径为10 nm的常规标记大10倍。在标记物用大磁场磁化后，该标记还可以保持remanent磁场。使用鱿鱼显微镜和新标记，我们可以检测到小至1 pg的标记。我们还进行了一次免疫测定实验。对于抗原，我们使用了称为IL8的蛋白质。目前，我们可以检测到IL8至1 pg。但是，我们可以期望从系统的噪声性能中检测到小于0.1 pg的IL8。由于底物的磁污染限制了目前的检测水平，因此我们必须解决此问题以检测0.1 pg的IL8。

项目成果

K. Enpuku, D. Kuroda, D. Tokimizu and T. Q. Yang: "Suppression of thermally activated flux entry through a flux dam in high T_c superconducting quantum interference device magnetometer"Journal of Applied Physics. vol. 92, no. 8. 4751-4757 (2002)

K. Enpuku、D. Kuroda、D. Tokimizu 和 T. Q. Yang：“高 T_c 超导量子干涉装置磁力计中热激活磁通进入磁通坝的抑制”应用物理学杂志。

K.Enpuku et al.: "Properties of a flux dam inserted in the pickup coil of a high T superconductirig quantum interference"Japanese Journal of Applied Physics. 40. 4013-4018 (2001)

K.Enpuku 等人：“插入高 T 超导量子干涉拾波线圈中的磁通坝的特性”日本应用物理学杂志。

K. Enpuku and T. Minotani: "Biological immunoassays with high T_c superconducting quantum interference device (SQUID) magnetometer"IEICE Transactions on Electronics. vol. ES4-C, no. 1. 43-48 (2001)

K. Enpuku 和 T. Minotani：“使用高 T_c 超导量子干涉装置 (SQUID) 磁力计进行生物免疫测定”IEICE Transactions on Electronics。

K.Enpuku et al.: "Suppression of thermally activated flux entry through a flux dam in high T_c superconducting quantum interference device magnetometer"Journal of Applied Physics. vol.92, no.8. 4751-4757 (2002)

K.Enpuku 等人：“高 T_c 超导量子干涉装置磁力计中热激活磁通进入磁通坝的抑制”应用物理学杂志。

K. Enpufcu, D. Kuroda, T. Q. Yang and K. Yoshinaga: "High T_c SQUID System and Magnetic Marker for Biological Immunoassays"IEEE Transactions on Applied Superconductivity. (to be published). (2003)

K. Enpufcu、D. Kuroda、T. Q. Yang 和 K. Yoshinaga：“用于生物免疫测定的高 T_c SQUID 系统和磁性标记”IEEE 应用超导汇刊。