In this talk, I will review recent progress in biosensing using SQUID and magnetic markers. Magnetic markers consisting of polymer-coated magnetic nanoparticles have been widely used for biomedical applications. In biomedical diagnosis, a detecting antibody, which is conjugated on the surface of the marker, is bound to a biological target. The binding reaction between them is detected with the magnetic signal from the bound markers. Since the signal from the bound markers becomes very weak at early stage of disease, it is necessary to develop highly sensitive detection system. Several SQUID systems have so far been developed for this purpose. Measurement methods, including AC susceptibility, harmonic signal, magnetic relaxation and remanence, have also been developed, depending on the properties of the markers. The SQUID systems have been applied to both in vitro and in vivo diagnosis and high sensitivity of the system has been successfully demonstrated by the detection of several disease-related proteins. For in vitro diagnosis, magnetic immunoassay techniques have been developed for liquid-phase detection of biological targets. With this method, we can magnetically distinguish bound and unbound (free) markers by using the Brownian relaxation of the markers. As a result, we can eliminate time-consuming washing processes for marker separation, unlike the case of the conventional optical method. This method also allows the study of how the binding of targets and markers proceeds in time, i.e., perform a quantitative evaluation of the binding kinetics. For in vivo diagnosis, the position and quantity of the markers, which have accumulated in the affected area inside an animal or human body, are detected. This method is called magnetic particle imaging (MPI). When we apply MPI to the detection of breast cancer or sentinel lymph node, it is necessary to detect the markers locating at 3 to 5 cm in depth. The small amount of markers, e.g.. 1 g, should be detected with reasonable spatial resolution. Several systems have been developed for this purpose.
Perspectives on the 50th Anniversary of SQUIDs (Superconducting Quantum Interference Devices) by Keiji Enpuku