Characterization of single-core magnetite nanoparticles for magnetic imaging by SQUID relaxometry

Abstract

Optimizing the sensitivity of SQUID (superconducting quantum interference device)-relaxometry for detecting cell-targeted magnetic nanoparticles for in vivo diagnostics requires nanoparticles with a narrow particle size distribution to ensure that the Néel relaxation times fall within the measurement timescale (50 ms - 2 s, in this work). To determine the optimum particle size, single-core magnetite nanoparticles (with nominal average diameters 20, 25, 30, and 35 nm) were characterized by SQUID-relaxometry, transmission electron microscopy (TEM), SQUID-susceptometry, dynamic light scattering, and zeta potential analysis. The SQUID-relaxometry signal (detected magnetic moment/kg) from both the 25 nm and 30 nm particles was an improvement over previously-studied multi-core particles. However, the detected moments were an order of magnitude lower than predicted based on a simple model that takes into account the measured size distributions (but neglects dipolar interactions and polydispersity of the anisotropy energy density), indicating that improved control of several different nanoparticle properties (size, shape, coating thickness) will be required to achieve the highest detection sensitivity. Antibody conjugation and cell incubation experiments show that single-core particles enable a higher detected moment per cell, but also demonstrate the need for improved surface treatments to mitigate aggregation and improve specificity.

Magnetic relaxometry as applied to sensitive cancer detection and localization

“…Helmholtz magnetizing coils with a diameter of 65 cm and 100 turns, aligned along the central axis of the sensor array, powered by a 5-kW current-regulated supply (Sorenson SGA 80/63, San Diego, CA, USA) orient the total magnetization vector of the NP ensemble along the z-axis of the sensor system during the pulse and before the decay begins. The magnetizing pulse is typically 4 mT and is applied for 0.75 s. To allow induced currents in the components of the SQUID sensor array and the environment to decay following the magnetizing pulse, a delay of 35 ms was incurred before turning on the SQUID sensors, followed by a measurement of the decaying magnetic field from the NPs for 2.2 s [2,9]. To increase the signal-to-noise ratio, this sequence was repeated ten times, and the result signal averaged.…”

“…Relaxation of the induced moments can take place by one of two mechanisms: Brownian motion of unbound particles through the surrounding medium, or Néel relaxation [18] of particles bound to cells, whereby relaxation occurs by reorientation of the electron orbits within the NPs. Néel relaxation has a strong (exponential) dependence on the particle volume, so it is critical that the NP diameter falls within a narrow range, approximately 24-26 nm, to ensure that the relaxation is detectable on the timescale of the measurement [2]. For 24-26 nm Fe 3 O 4 NPs in a physiological medium, Brownian and Néel processes occur on substantially different time scales.…”

A quantitative study of particle size effects in the magnetorelaxometry of magnetic nanoparticles using atomic magnetometry

“…From Eqs. (13), (15) and (16) it follows that the (orientationally averaged) magnetic moment per particle at time t is then given by…”

“…The property was used, e.g., to image the accumulation of intravenously injected SPIONs in the spleen and liver of a mouse by MRX [13], or to quantify the aggregation of magnetic nanoparticles in cell cultures [14]. Many of the earlier studies used multi-core particles, while more recently larger single-core magnetic particles have shown large magnetic signals in observation windows ranging from 50 ms to 2 s [15]. Those and others studies [16][17][18] have demonstrated that (SQUID-based) MRX has a high potential for biomedical imaging applications.…”

Nanopharmaceuticals (part 2): products in the pipeline

“…38 Anti-CD34-conjugated NPs can be prepared by incubating carboxyl groups-bearing commercially available magnetite NPs at an acidic pH and room temperature with EDC and N-hydroxysulfosuccinimide, followed by raising the pH to 8 and adding the anti-CD34 antibody. 38,39 TEM studies have shown that the conjugation reaction has no impact on the Ferret diameter of the commercially available NPs. The surface modification with protein (CD34 antibodies), however, increases the particle's hydrodynamic diameter to approximately 70 nm, when measured by DLS.…”