(Invited) Biological Applications of Magnetic Nanoparticles for Magnetic Immunoassay and Magnetic Particle Imaging

Abstract

Iron oxide magnetic nanoparticles (MNPs), whose typical sizes are in the range of few nanometers to tens of nanometers, are widely studied for biological applications because they offer some attractive possibilities. First, their size can be controllable in order that they can get close to a biological target of interest. Being coated with biological molecules, MNPs can bind to a biological target. Second, they can be manipulated at a distance using an external magnetic field gradient. Third, the MNPs respond to an AC magnetic field and exhibit different responses depending on their size, the frequency of the magnetic field, and so on. Owing to these attractive properties of the MNPs, many researchers have explored the biological applications of the MNPs such as the separation of biological targets, drug delivery, immunoassay, hyperthermia, and magnetic particle imaging (MPI) for biomedical imaging [1]. In this presentation, we focus on the applications of the MNPs for immunoassay and MPI.Immunoassay is a detection of biological target, such as disease related proteins and cells, for medical diagnosis. We developed a magnetic immunoassay system utilizing magnetic markers [2]. In this method, the marker is made of MNPs coated with antigen-specific antibodies. The markers coupled to the biological target are detected by measuring the magnetic signal from the bound marker. One of the advantages of the magnetic method is that we can perform immunoassay in the liquid phase, i.e., we can magnetically distinguish bound markers, which are coupled to the biological target, from unbound (free) markers without utilizing a time-consuming washing process called B/F separation. This function can be realized by using the difference in Brownian relaxation time between the bound and free markers [2]. So far we performed a magnetic immunoassay using streptavidin coated magnetic markers, biotins as target which are fixed on the surface of large polymer beads, and anisotropic magneto-resistive sensors. The sensitivity was estimated as high as 10 fM in terms of the molecular-number concentration.MPI, which was introduced by Gleich and Weizenecker [3], is a new modality for imaging the spatial distribution of MNPs, especially for in-vivo diagnostics. Since the direct nonlinear magnetization signals from MNPs are sensitively detected with no background tissue signal, MPI could be applied for clinical applications such as angiography, stem cell tracking, and cancer imaging. The performance of MPI strongly depends on the magnetic properties of the MNPs, such as magnetic moment, relaxation time, and their distributions. In this presentation, we will show the method to estimate these important parameters and their distributions in MNPs sample [4]. We will also discuss how the viscosity of surrounding medium affects the dynamic magnetization properties of MNPs from the view point of sensitivity and spatial resolution of the image in MPI [5].