Biosensing utilizing magnetic markers and superconducting quantum interference devices

Abstract

Magnetic biosensing techniques that are based on the use of bio-functionalized magnetic nanoparticles (magnetic markers) and superconducting quantum interference devices (SQUIDs) are expected to have various advantages when compared with conventional biosensing methods. In this paper, we review the recent progress made in magnetic biosensing techniques. First, we describe the most important parameters of magnetic markers that are intended for use in biosensing, i.e., the magnetic signal and the relaxation time that are determined by the Brownian and/or Néel relaxation mechanisms. We note that these parameters are significantly dependent on the marker size, and as a result, commercial markers exhibit a wide variety of values for these key parameters. Next, we describe three measurement methods that have been developed based on the magnetic properties of these markers, i.e., AC susceptibility, relaxation and remanence-based measurement methods. The weak (picotesla-range) signals emitted by the markers can be measured precisely with a SQUID system using these methods. Finally, we give examples of biosensing for in vitro and in vivo medical diagnosis applications. For in vitro diagnosis, high-sensitivity detection of various biological targets has been demonstrated without use of any washing process to separate the bound and free markers. For in vivo applications, detection of the quantities and the three-dimensional positions of the markers that have been injected into the test subject are demonstrated. These results confirm the effectiveness of magnetic biosensing techniques.

Volume-amplified magnetic bioassay integrated with microfluidic sample handling and high-Tc SQUID magnetic readout

“…Proposed theoretically by Connolly and St Pierre (Connolly and St Pierre, 2001) and shown experimentally for prostate-specific antigen (PSA) and Brucella antibodies (Astalan et al , 2004; Fornara et al , 2008), the change in Brownian relaxation time due to binding to analytes was determined by measuring complex frequency dependent magnetic susceptibility. Examples of sensors that utilize this dynamic mechanism are high- T c superconducting quantum interference devices (SQUIDs) (Enpuku et al , 2017; Yang et al , 2013), the differential induction coil system DynoMag (RISE Acreo, Sweden) (Astalan et al , 2004; Zardán Gómez de la Torre et al , 2011), and opto-magnetic sensors (Donolato et al , 2015). These sensors exploit the three dimensions of sample volume for analyte and probe binding and measure the signal generated from the whole sample volume.…”

Characterization and Relaxation Properties of a Series of Monodispersed Magnetic Nanoparticles

“…This is also the basic principle of magnetic nanoparticles as contrast agents in MRI. It can be assumed that the magnetic field inhomogeneity is directly related to the induced magnetization produced by magnetic nanoparticles in magnetic field, and the induced magnetization can be described by the Langevin model [8,51,52,53,54]:M=Nm(coth(mBkT)−kTmB) where N is the number of magnetic nanoparticles per unit volume (i.e., the concentration of magnetic nanoparticles); m is the magnetic moment of a single magnetic nanoparticle; B is the static magnetic field; k is the Boltzmann constant and T is the absolute temperature.…”

Point-of-Care Diagnostics: Molecularly Imprinted Polymers and Nanomaterials for Enhanced Biosensor Selectivity and Transduction

“…Consider that an MNP's magnetic susceptibility, or the extent of magnetization versus applied magnetic field, can be correlated with the amount of analyte bound to a surrounding MIP layer (142). In that case, magnetic transduction strategies relying on magnetic relaxation, like SQUID (156,157) or Fluxgate biosensors (158,159), are expected to perform well with MIPs. Similarly, MIP functionalized MNPs should be amenable to a variety of magnetoresistance transduction strategies like GMR (160,161).…”