Biosensing Using Magnetic Particle Detection Techniques

Abstract

Magnetic particles are widely used as signal labels in a variety of biological sensing applications, such as molecular detection and related strategies that rely on ligand-receptor binding. In this review, we explore the fundamental concepts involved in designing magnetic particles for biosensing applications and the techniques used to detect them. First, we briefly describe the magnetic properties that are important for bio-sensing applications and highlight the associated key parameters (such as the starting materials, size, functionalization methods, and bio-conjugation strategies). Subsequently, we focus on magnetic sensing applications that utilize several types of magnetic detection techniques: spintronic sensors, nuclear magnetic resonance (NMR) sensors, superconducting quantum interference devices (SQUIDs), sensors based on the atomic magnetometer (AM), and others. From the studies reported, we note that the size of the MPs is one of the most important factors in choosing a sensing technique.

Keywords: GMR; NMR; SQUID; atomic magnetometer; magnetic particles; molecular sensing; spintronic sensors.

Figure 1

(a) Illustration of the behavior of the magnetic dipole moments in five types of magnetic materials with and without an external magnetic field (H). (b) Schematic of typical magnetization curves generated by an applied magnetic field. The general hysteresis loop shows the relationship of magnetization versus the applied magnetic field. The curved slope defines the magnetic susceptibility of the material. (c) A non-hysteretic magnetic curve of a superparamagnetic material. Reproduced with permission from [28], copyright 2007 Wiley, and from [8], copyright 2009 The Royal Society of Chemistry.

Figure 2

Design of magnetic particles for biosensing.

Figure 3

Examples of preparation methods for MPs embedded in silica and polymer matrices: (a) layer-by-layer synthesis of gold-coated silica-core MPs, (b) TEM image of SiO₂@Fe₃O₄@Au_seeds, (c) MPs attracted to the vessel wall by a magnet, (d) preparation of polymer composite magnetic particles by the swelling method, and (e,f) SEM image of polymer-embedded MPs. Reproduced with permissions from [72], copyright 2005 American Chemical Society, and from [73], copyright 2012 Royal Society of Chemistry.

Figure 4

(a) Illustration of the preparation of Fe₃O₄@Au@mSiO₂-dsDNA/DOX nanoparticles for in vivo treatment of cancer cells, (b) TEM image of Fe₃O₄@Au, and (c) TEM image of Fe₃O₄@Au@mSiO₂. Reproduced with permission from [103], copyright 2014 American Chemical Society.

Figure 5

GMR applications: (a) optical image of GMR sensor architecture, where the upper right inset shows the SEM image of one strip with several bound MPs, (b) illustration showing the magnetic particle detection process, (c) real-time binding curve with fitting, and (d) SEM image of a section of the GMR sensor. Reproduced with permission from [12], copyright 2011 Nature Publishing Group.

Figure 6

(a) Relaxation biosensor in NMR. (b) The magnetic switch application in magneto-DNA assay. (c) Capture bead and MP probe under TEM (left, scale bar, 100 nm), SEM (middle, scale bar 300 nm), and AFM (right, scale bar 100 nm). Reproduced with permission from [210], copyright 2014 American Chemical Society, and [40], copyright 2013 Nature Publishing Group.

Figure 7

An example application of SQUID: (a) an applied magnetic field aligns the magnetic moment of MPs conjugated with an antibody, which are added into a bacteria-laden liquid suspension, (b) after removing the magnetic field, the unbound MPs have randomized magnetic moments due to Brownian rotation while the bound MPs slowly relax by Néel relaxation, and (c) magnetic decay signals including bacteria and unbound MPs. Insert: configuration of the YBCO SQUID. Reproduced with permission from [186], copyright 2004 National Academy of Sciences, U.S.A.

Figure 8

FIRMS studies using DNA: (a) a schematic of the FIRMS setup for DNA duplexes, (b) a photo of the sample well, (c) two DNA duplexes distinguished in a plot of magnetization versus force, and (d) the principle of acoustic radiation force (top figure) and an illustration binding profile of two DNA duplexes with the plot of magnetic field versus ultrasound power. Reproduced with permissions from [194], copyright 2014 Royal Society of Chemistry and from ref. [195], and copyright 2013 American Chemical Society.