Khurshid Hafsa, Friedman Bruce, Berwin Brent, Shi Yipeng, Ness Dylan B, Weaver John B
Department of Radiology, Dartmouth-Hitchcock Medical Center , Lebanon New Hampshire 03756, USA.
Cardiology Department, Dartmouth-Hitchcock Medical Center , Lebanon New Hampshire 03756, USA.
AIP Adv. 2017 Feb 16;7(5):056723. doi: 10.1063/1.4977073. eCollection 2017 May.
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. , 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.
深静脉血栓形成，即外周静脉中血凝块的形成，是一种非常严重、危及生命的疾病，在老年人中很常见。为了提供能提高存活率的恰当治疗，在护理点早期检测血栓非常重要。我们探索了磁粒子光谱法（MSB）通过适配体功能化磁性纳米颗粒与血凝块的特异性结合来检测血栓的能力。MSB利用纳米颗粒在交变磁场中产生的谐波来测量其旋转自由度，进而测量纳米颗粒的结合状态。当纳米颗粒结合时，其布朗旋转的弛豫时间会增加[A.M. 劳韦尔丁克和J.B. 韦弗，《应用物理快报》，1（2010）]。因此，弛豫时间可用于表征纳米颗粒与血凝块中凝血酶的结合情况。对于较长的弛豫时间，达到饱和的过程更为平缓，会降低高次谐波和谐波比。与未结合抗凝血酶适配体（ATP）的纳米颗粒相比，结合了抗凝血酶适配体的纳米颗粒的谐波比会随着样品介质中存在血凝块而随时间显著降低。此外，从样品介质中取出的血凝块产生了显著的MSB信号，表明纳米颗粒固定在了血凝块上。我们的结果表明，MSB可能是一种非常有用的非侵入性快速工具，可在护理点检测血凝块，从而能够采用恰当的治疗方法来降低深静脉血栓形成所固有的风险。
