Philips Chair of Medical Information Technology, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany.
Biosens Bioelectron. 2011 Aug 15;26(12):4702-7. doi: 10.1016/j.bios.2011.05.028. Epub 2011 May 23.
Pathological calcification of the cardiovascular system is one of the major causes of high mortality and morbidity in dialysis patients. The inhibition of ectopic calcification relies (I) on the formation of calciprotein particles (CPPs), nanospherical complexes of calcium phosphate mineral, fetuin-A and other acidic serum proteins, and (II) on the stabilization of calcium phosphate prenucleation clusters by fetuin-A monomers. In supersaturated serum, mineral ion aggregation leads to a change in the electrical impedance. In this work, we present a method based on electrochemical impedance spectroscopy (EIS) to establish an impedance trace of mineral ion clustering in vitro. In the presence of 20 μM of serum protein fetuin-A, a prototypic calcification inhibitor, we measured a change in impedance (Δ(R)) of 195.52 ± 27.78%Ω compared to 430.41 ± 11.36%Ω in inhibitor-free samples. We also identified a CPP-formation dependency on the actual content of ions and protein in the samples under investigation. Two-step ripening of CPP was also observed. The presented method may form the basis of a simple label-free bedside or online test to be used in routine clinical practice for estimating the calcification risk in serum.
心血管系统的病理性钙化是透析患者高死亡率和高发病率的主要原因之一。异位钙化的抑制依赖于：(I) 钙磷矿物、胎球蛋白-A 和其他酸性血清蛋白的纳米球复合钙蛋白颗粒（CPPs）的形成，和 (II) 胎球蛋白-A 单体对磷酸钙成核前体簇的稳定。在过饱和的血清中，矿物质离子聚集会导致电阻抗发生变化。在这项工作中，我们提出了一种基于电化学阻抗谱（EIS）的方法，以建立体外矿物质离子聚集的阻抗轨迹。在存在 20 μM 血清蛋白胎球蛋白-A（典型的钙化抑制剂）的情况下，与无抑制剂样品的 430.41 ± 11.36%Ω相比，我们测量到阻抗（Δ(R)）的变化为 195.52 ± 27.78%Ω。我们还确定了 CPP 形成对样品中实际离子和蛋白质含量的依赖性。还观察到 CPP 的两步熟化。所提出的方法可以作为一种简单的无标记床边或在线测试的基础，用于常规临床实践中估计血清中的钙化风险。
