Impedimetric Biosensors for Detecting Vascular Endothelial Growth Factor (VEGF) Based on Poly(3,4-ethylene dioxythiophene) (PEDOT)/Gold Nanoparticle (Au NP) Composites
Impedimetric Biosensors for Detecting Vascular Endothelial Growth Factor (VEGF) Based on Poly(3,4-ethylene dioxythiophene) (PEDOT)/Gold Nanoparticle (Au NP) Composites
复制标题
DOI：
10.3389/fchem.2019.00234
复制
发表时间：
2019-04-16
影响因子：
5.5
通讯作者：
Martin, David C.
中科院分区：
文献类型：
--
作者：
Kim, Minsoo;Iezzi, Raymond, Jr.;Martin, David C.
在糖尿病视网膜病变、视网膜血管闭塞性疾病和渗出性年龄相关性黄斑变性的晚期形式中，视力丧失与血管内皮衍生生长因子（VEGF）水平升高或外渗到眼睛的视网膜、玻璃体和前房中相关。我们假设，能够快速精确测量眼内VEGF水平的即时生物传感器将有助于临床医生评估疾病严重程度，并建立眼内抗VEGF注射治疗的个体化给药间隔。建立了一种基于聚3，4-乙撑二氧噻吩（PEDOT）/纳米金（Au NP）复合物的阻抗生物传感器，用于检测血管内皮生长因子（VEGF）。将具有Au NP的PEDOT电化学沉积在三种不同的医疗电极传感器设计上：独立垫、丝网印刷点和交叉指状微带电极。抗VEGF抗体通过与柠檬酸盐官能化的Au NPs连接而共价固定在聚合物膜的表面上，并且所得复合材料用于通过电化学阻抗谱（EIS）检测VEGF-165。采用光学显微镜、SEM/EDS、FIB、TEM和STEM技术对PEDOT-Au NP复合材料进行了表征。在不同的微电极中，交叉指状条形状显示出最好的整体膜稳定性和再现性。在电荷转移电阻（R-ct）与VEGF浓度之间建立线性关系。发现VEGF的检测限为0.5 pg/mL，相关系数为0.99 +/-0.064%。这些结果表明，所提出的PEDOT/Au NP复合物可用于设计低成本和精确的VEGF生物传感器，用于诸如VEGF介导的眼部疾病的临床诊断。
In advanced forms of diabetic retinopathy, retinal vascular occlusive disease and exudative age-related macular degeneration, vision loss is associated with elevated levels or extravasation of vascular endothelial-derived growth factor (VEGF) into the retina, vitreous, and anterior chamber of the eye. We hypothesize that point-of-care biosensors, capable of rapidly and precisely measuring VEGF levels within the eye will assist clinicians in assessing disease severity, and in establishing individualized dosing intervals for intraocular anti-VEGF injection therapy. An impedance biosensor based on a poly(3,4-ethylenedioxythiophene) (PEDOT)/gold nanoparticle (Au NP) composite was developed for detecting VEGF. PEDOT with Au NP was electrochemically deposited on three different medical electrode sensor designs: free-standing pads, screen printed dots, and interdigitated micro-strip electrodes. Anti-VEGF antibody was covalently immobilized on the surface of the polymer films through attachment to citrate-functionalized Au NPs, and the resulting composites were used to detect VEGF-165 by electrochemical impedance spectroscopy (EIS). The PEDOT-Au NP composite materials were characterized using optical microscopy, SEM/EDS, FIB, TEM, and STEM techniques. Among the different micro-electrodes, the interdigitated strip shape showed the best overall film stability and reproducibility. A linear relationship was established between the charge transfer resistance (R-ct) and VEGF concentration. The detection limit of VEGF was found to be 0.5 pg/mL, with a correlation coefficient of 0.99 +/- 0.064%. These results indicate that the proposed PEDOT/Au NP composites can be used in designing low-cost and accurate VEGF biosensors for applications such as clinical diagnosis of VEGF-mediated eye disease.