Nanoparticle−Target Interactions Parallel Antibody−Protein Interactions

Abstract

Magnetic particles can act as magnetic relaxation switches (MRSw's) when they bind to target analytes, and switch between their dispersed and aggregated states resulting in changes in the spinspin relaxation time (T 2 ) of their surrounding water protons. Both nanoparticles (NPs, 10-100 nm) and micron-sized particles (MPs) have been employed as MRSw's, to sense drugs, metabolites, oligonucleotides, proteins, bacteria and mammalian cells. To better understand how NPs or MPs interact with targets, we employed as a molecular recognition system the reaction between the Tag peptide of the influenza virus hemagglutinin and a monoclonal antibody to that peptide (anti-Tag). To obtain targets of different size and valency, we attached the Tag peptide to BSA (Mw= 65000 Daltons, diameter = 8 nm) and to Latex spheres (diameter = 900 nm). To obtain magnetic probes of very different sizes, anti-Tag was conjugated to 40 nm NPs and 1 μm MPs. MP and NP probes reacted with Tag peptide targets in a manner similar to antibody/antigen reactions in solution, exhibiting socalled prozone effects. MPs detected all types of targets with higher sensitivity than NPs with targets of higher valency being better detected than those of lower valency. The Tag/anti-tag recognition system can be used to synthesize combinations of molecular targets and magnetic probes, to more fully understand the aggregation reaction that occurs when probes bind targets in solution and the ensuing changes in water relaxation times that result.

Nuclear Magnetic Resonance Nanotechnology: Applications in Clinical Diagnostics and Monitoring

“…They suggest that potential factors to improve on this are polycrystalline superparamagnetic particles and magnetic field facilitated cluster formation to form larger clusters, which is consistent with previous work using MPs for highsensitivity immunoassay detection to achieve sensitivity levels below 100 fM. (31,32,35) …”

“…These include a study where particle valency was demonstrated to play a key role in MRSw assay sensitivity for the detection of cellular targets. (30) The underlying dependence of particle and target valency, as well as particle and target size, was systematically explored by Koh et al (31) In this work, Koh et al simplified the comparison of target size and valency and particle size effects on T 2 by using the same binding moiety to induce clustering for all reagent types. Clustering of NPs and micrometer-sized particles (MPs) was induced by the binding of the Tag peptide of the influenza virus hemaglutinin by particle-anchored antiTag monoclonal antibodies.…”

Resistive pulse sensing of magnetic beads and supraparticle structures using tunable pores

“…56 For applications in which target analytes contain multiple binding sites or epitopes, it is possible for the target to bind to multiple beads simultaneously, leading to aggregation. 41,[57][58][59] Multiple-particle binding has been used in LM, allowing detection of the dengue virus at 10 plaque forming units ml À1 . 41 Alternative methods monitor aggregation using chain length, 60 turbidity, 57 or changes in magnetic properties when particles are in close proximity to each other.…”

“…41 Alternative methods monitor aggregation using chain length, 60 turbidity, 57 or changes in magnetic properties when particles are in close proximity to each other. 58 The fundamental reason for the high utility of SPMs is that the physics of bead manipulation is independent of usual microfluidic and biological processes. 40 In resistive pulse sensing, physical mechanisms for driving particles through the constriction can be summarized by Nernst-Planck theory, which gives the particle flux through a pore,…”

Blu-ray based optomagnetic aptasensor for detection of small molecules

“…The latter typically employs sandwich binding-induced clustering where a molecule of interest is bound to multiple receptors tethered onto MNP surfaces, resulting in the agglutination of MNPs. Accordingly, the addition of a target triggers clustering of MNPs, leading to changes in the size and the number of agglomerated particles with the analyte concentration, which is referred to as a clustering assay (Aurich et al 2006;Baudry et al 2006;Castañeda et al 2007;Göransson et al 2010;Josephson et al 2001;Koh et al 2009;Liang et al 2011;Ling et al 2010;Perez et al 2002;Ranzoni et al 2012;Zhang et al 2013a). Such a volume-based MNP clustering assay is particularly appealing since it allows simple mix-and-read type measurements and reduced reaction time by use of external magnetic fields (Baudry et al 2006).…”