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.
Highlights
Thrombin is a coagulation serine protease that plays a key role in thrombogenesis/hemostasis, which is the process that halts bleeding secondary to blood vessel damage.[2]
For the magnetic nanoparticles (MNPs) without any blood clot, the second harmonic does not change over the time and MNPs are stable over the time
MNPs with the clot produced harmonic ratios that dropped over the time and eventually reached an equilibrium state
Summary
Hafsa Khurshid,[1] Bruce Friedman,[2] Brent Berwin,[3] Yipeng Shi,[4] Dylan B. Ness,[1] and John B. Weaver1,5 1Department of Radiology, Dartmouth-Hitchcock Medical Center, Lebanon New Hampshire 03756, USA 2Cardiology Department, Dartmouth-Hitchcock Medical Center, Lebanon New Hampshire 03756, USA 3Department of Microbiology and Immunology, Geisel School of Medicine, Hanover New Hampshire 03755, USA 4Department of Physics & Astronomy, Dartmouth College, Hanover New Hampshire 03755, USA 5Thayer School of Engineering, Dartmouth College, Hanover New Hampshire 03755, USA (Presented 2 November 2016; received 23 September 2016; accepted 17 November 2016; published online 16 February 2017)
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