Blood clot detection using magnetic nanoparticles

Abstract

Deep vein thrombosis, the development of blood clots in the peripheral veins, is a very serious, life threatening condition that is prevalent in the elderly. To deliver proper treatment that enhances the survival rate, it is very important to detect thrombi early and at the point of care. We explored the ability of magnetic particle spectroscopy (MSB) to detect thrombus via specific binding of aptamer functionalized magnetic nanoparticles with the blood clot. MSB uses the harmonics produced by nanoparticles in an alternating magnetic field to measure the rotational freedom and, therefore, the bound state of the nanoparticles. The nanoparticles’ relaxation time for Brownian rotation increases when bound [A.M. Rauwerdink and J. B. Weaver, Appl. Phys. Lett. 96, 1 (2010)]. The relaxation time can therefore be used to characterize the nanoparticle binding to thrombin in the blood clot. For longer relaxation times, the approach to saturation is more gradual reducing the higher harmonics and the harmonic ratio. The harmonic ratios of nanoparticles conjugated with anti-thrombin aptamers (ATP) decrease significantly over time with blood clot present in the sample medium, compared with nanoparticles without ATP. Moreover, the blood clot removed from the sample medium produced a significant MSB signal, indicating the nanoparticles are immobilized on the clot. Our results show that MSB could be a very useful non-invasive, quick tool to detect blood clots at the point of care so proper treatment can be used to reduce the risks inherent in deep vein thrombosis.

Evaluating blood clot progression using magnetic particle spectroscopy

“…The aptamer‐treated MNPs bind to the specific exosites at the thrombin molecule on the blood clot and hence their physical rotation is restricted. In contrast, when MNPs are used without the aptamer targeting, the relaxation time changed very little and the drop in MSB harmonic ratios was minimal …”

“…To probe the MNPs’ binding to thrombi, the MNPs were functionalized with ATP15 and ATP29 aptamers (BasePair Biotechnologies, Pearland, TX, USA), which bind to two distinct epitopes on thrombin. The MNPs bound to thrombus were identified by the reduction in their relaxation time measuring their reduced Brownian rotational freedom using MSB . The ratio of harmonics is a metric for the rotational freedom of motion, which in turn reflects the bound state of the MNPs …”

“…The MNPs bound to thrombus were identified by the reduction in their relaxation time measuring their reduced Brownian rotational freedom using MSB. 11,12 The ratio of harmonics is a metric for the rotational freedom of motion, which in turn reflects the bound state of the MNPs. 11 Higher harmonics in the MNPs' magnetization are uniquely associated with the MNPs, similar to magnetic particle imaging (MPI).…”

“…They have also functioned as biocompatible thrombolytic agents and have been successfully used to accelerate blood clot lysis using localized hyperthermia . Previous efforts have also used magnetic particle spectroscopy (MPS) to characterize blood clot lysis using MNP hyperthermia and to quantify the amount of iron on the clot Recently, magnetic spectroscopy of MNP Brownian rotation (MSB) has been shown to be a useful tool for the detection and characterization of blood clots and hence it has the potential to characterize thrombus to treat DVT more effectively and reduce the risks . MSB is a form of magnetic particle spectroscopy sensitive to Brownian rotation of MNPs, which allows for quantization of binding and temperature effects .…”

“…8 Previous efforts have also used magnetic particle spectroscopy (MPS) to characterize blood clot lysis using MNP hyperthermia and to quantify the amount of iron on the clot 9,10 Recently, magnetic spectroscopy of MNP Brownian rotation (MSB) has been shown to be a useful tool for the detection and characterization of blood clots and hence it has the potential to characterize thrombus to treat DVT more effectively and reduce the risks. 11 MSB is a form of magnetic particle spectroscopy sensitive to Brownian rotation of MNPs, which allows for quantization of binding and temperature effects. [12][13][14] For in vivo applications, to detect and quantitatively characterize blood clot stiffness, age, and the number of MNPs in the microenvironment of the thrombus.…”