Magnetic particle detection (MPD) for in-vitro dosimetry

Abstract

In-vitro tests intended for evaluating the potential health effects of magnetic nanoparticles generally require an accurate measure of cell dose to promote the consistent use and interpretation of biological response. Here, a simple low-cost inductive sensor is developed for quickly determining the total mass of magnetic nanoparticles that is bound to the plasma membrane and internalized by cultured cells. Sensor operation exploits an oscillating magnetic field (f0 = 250 kHz) together with the nonlinear response of particle magnetization to generate a harmonic signal (f3 = 750 kHz) that varies linearly with particulate mass (R2 > 0.999) and is sufficiently sensitive for detecting ~100 ng of carboxyl-coated iron-oxide nanoparticles in under a second. When exploited for measuring receptor-mediated nanoparticle uptake in RAW 264.7 macrophages, results show that the achieved dosimetric performance is comparable with relatively expensive analytical techniques that are much more time-consuming and labor-intensive to perform. The described sensing is therefore potentially better suited for low-cost in-vitro assays that require fast and quantitative magnetic particle detection.

Iron oxide nanoparticle agglomeration influences dose rates and modulates oxidative stress-mediated dose–response profilesin vitro

“…IONPs agglomerates were incubated with C10 lung epithelial cells cultured as a monolayer, and the amount of IONP associated with cells (cellular dose) was quantified as a function of exposure concentration and time using a MPD system developed in our lab (Ferguson et al 2011; Minard et al 2012). An important advantage of this method of quantification is that the superparamagnetic properties detected by MPD rely on iron being in particulate form (Ferguson et al 2011), allowing unambiguous measurements of intact IONP versus ionic forms of iron that are relatively abundant in biological systems.…”

“…The proper attribution of physical or chemical characteristics of nanoparticles to specific biological effects therefore requires careful consideration of the cellular dose. MPD provided a reliable method to quantify the total amount of IONP bound and internalised in cells, since the MPD sensor mechanism is sensitive to magnetisation signals from iron only when it is bound in particulate form (Ferguson et al 2011; Minard et al 2012). Our recent work has shown that MPD is sufficiently sensitive to quantify ~100 ng of superparamagnetic IONPs, and can even discriminate differences in rates of total cell binding/uptake of IONPs due to expression of specific endocytic receptors (Minard et al 2012).…”

“…The cellular content of IONP agglomerates was measured using a custom-built magnetic particle detector as described previously (Hinderliter et al 2010; Minard et al 2012). The detection system measures iron oxide associated with particles, but not dissolved iron species, which lack the superparamagnetic property required for detection.…”

“…Using IONPs with two surface modifications (carboxylated, aminated), this strategy was applied to create stable agglomerates with diameters ranging from 276 nm to 1.5 μm which have protein coronas from a common serum protein source and bear similar net zeta potentials in conventional culture medium. IONPs also provide a useful model nanoparticle which permitted us to directly quantify cell dose using a magnetic particle detection (MPD) system recently developed at their laboratory (Minard et al 2012; Ferguson et al 2011). MPD exploits an oscillating magnetic field together with the non-linear response of particle magnetisation to quantify superparamagnetic particle mass in biological samples.…”

Design and simulation of magnetic nanoparticles detector based on the nonlinear magnetization

“…The vitro methods of the detection of magnetic nanoparticles are atomic absorption spectrometry [2], electron paramagnetic resonance [3], and inductively coupled plasma mass spectrometry [4]. The methods of quantitative measurement of concentration of the magnetic nanoparticles by measuring the magnetic response in alternating magnetic field are susceptometry and relaxometry.…”