SQUID Microscope System for Biological Immunoassay

在本项目中，我们开发了一套用于生物免疫分析的鱿鱼显微镜系统。在该系统中，抗体被标记上所谓的磁性标记物，通过测量来自该标记物的磁性信号来检测抗原与其抗体之间的结合反应。利用高灵敏度的SQUID传感器可以测量非常微弱的磁信号，我们可以检测到非常微小的结合反应。由于鱿鱼必须冷却到T=77K，我们研制了鱿鱼显微镜，使鱿鱼与室温样品之间的距离可以小于1 mm。我们还利用直径为25 nm的Fe_3O_4磁性纳米粒子研制了一种新的标记。该标记器可以产生比传统直径为10 nm的标记器大10倍的磁信号。该标记器还能在大场磁化后保持剩余磁场。使用鱿鱼显微镜和新的标记，我们可以检测到小到1pg的标记。我们还做了免疫分析实验。对于抗原，我们使用了名为IL8的蛋白质。目前，我们可以检测到小到1pg的IL8。然而，我们可以从系统的噪声性能中检测到IL8小于0.1pg。由于衬底的磁性污染限制了目前的检测水平，为了检测0.1pg的IL8，我们必须解决这个问题。

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.