Magnetic immunoassay system utilizing magnetic marker and SQUID sensor

免疫分析被广泛用于医学诊断中检测与疾病相关的蛋白质。这些蛋白质统称为抗原，所谓的抗原与其抗体之间的结合反应被用于免疫分析。为了提高免疫分析的性能，我们开发了一种新的检测系统，该系统使用了一个磁性标记和一个鱿鱼传感器。本研究取得的主要结果如下：(1)阐明了磁性纳米粒子的大小对磁性的影响。我们发现，名义直径为25 nm的颗粒可以保持剩磁，并能产生大的磁信号。因此，该磁性颗粒适合用于磁性免疫分析。(2)我们开发了一种用聚合物包覆磁性颗粒的工艺。利用这一工艺，我们制备了聚合物包覆的磁性纳米粒子，在液体中表现出良好的分散性。(3)研制了用于检测来自标记器的磁信号的高T_c SQUID系统。由于信号在空间中衰减很快，我们实现了冷却后的鱿鱼与室温样品的距离很近。(4)研制了一种无磁污染的反应室，并提出了消除环境噪声的方法，以检测到非常微弱的信号。我们的系统可以在短短几分钟的测量时间内检测到12个样品，场分辨率约为10PT。(5)我们进行了一种名为IgE的蛋白质检测。我们证明了对IgE的检测可以低至0.3pg，这表明了本磁法的高灵敏度。我们还验证了人血清中IgE的检测，这表明了将其用于实际诊断的可能性。

Immunoassays are widely used to detect disease-related proteins for medical diagnostics. These proteins are generically called antigens, and the so-called binding reaction between antigen and its antibody is used for the immunoassay. In order to improve the performance of the immunoassay, we have developed a new detection system utilizing a magnetic marker and a SQUID sensor. The main results obtained in this study are as follows.(1)We clarified the dependence of the magnetic properties on the size of the magnetic nanoparticle. We showed that the particle with nominal diameter of 25 nm can keep remanence, and can generate large magnetic signal. This particle is, therefore, suitable for magnetic immunoassay.(2)We developed a coating process to cover the magnetic particle with polymer. With this process, we fabricated a polymer-coated magnetic nanoparticle that shows good dispersion in liquid.(3)We developed the high Tc SQUID system for detecting magnetic signal from the marker. Since the signal decays rapidly in space, we realized a close distance between the cooled SQUID and the room temperature sample.(4)We developed a magnetic-contamination free reaction chamber and a method to cancel environmental noise in order to detect very weak signal. Our system can detect 12 samples in a short measurement time of a few minutes with a field resolution of about 10 pT.(5)We conducted a detection of protein called IgE. We demonstrated the detection of IgE down to 0.3 pg, which shows the high sensitivity of the present magnetic method. We also demonstrated the detection of IgE in human serum, which shows the possibility to practical diagnosis.