Turan Kübra, Aydoğdu TiĞ Gözde
Ankara University, Faculty of Science, Department of Chemistry, Ankara 06100, Türkiye.
ACS Omega. 2025 May 16;10(20):20907-20921. doi: 10.1021/acsomega.5c02339. eCollection 2025 May 27.
Neurodegenerative diseases (NDDs), among which Alzheimer's disease (AD) is one of the most significant medical and societal challenges of this century due to its increasing prevalence, require early diagnosis through reliable biomarkers to improve disease management. Among several biomarkers, kynurenic acid (KYNA) has emerged as a newly found metabolite, identified as a sensitive and selective blood-based biomarker, with its levels increasing in the early stages of AD. In this study, we aim to develop a low detection limit, stable, low-cost, and reliable molecularly imprinted polymer-based electrochemical biosensor for the rapid, selective, and sensitive detection of KYNA, a promising biomarker for AD. For this purpose, the glassy carbon electrode was first modified with copper-silver bimetallic structures (Cu-Ag BS). Then, a 3,4-ethylene-dioxythiophene (EDOT) monomer was electropolymerized on the Cu-Ag BS/GCE in the presence of the KYNA analyte. The introduced sensor was characterized through field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). The effect of electrodeposition parameters was optimized. This is the first time the proposed MIP sensor allowed KYNA detection in a wide linear range of 1.0 fM-500 nM with a limit of detection (LOD) of 0.278 fM. Furthermore, the MIP layer provides highly selective binding by forming KYNA-specific recognition cavities. Notably, the sensor has been successfully validated in complex biological media, including fetal bovine serum and human serum, achieving high recovery values. The proposed sensor could potentially be utilized in the future design of a diagnostic kit for the early diagnosis of neurodegenerative diseases.
神经退行性疾病（NDDs），其中阿尔茨海默病（AD）因其患病率不断上升，是本世纪最重大的医学和社会挑战之一，需要通过可靠的生物标志物进行早期诊断以改善疾病管理。在几种生物标志物中，犬尿喹啉酸（KYNA）已成为一种新发现的代谢物，被确定为一种敏感且具有选择性的血液生物标志物，其水平在AD早期会升高。在本研究中，我们旨在开发一种检测限低、稳定、低成本且可靠的基于分子印迹聚合物的电化学生物传感器，用于快速、选择性且灵敏地检测KYNA，这是一种有前景的AD生物标志物。为此，首先用铜 - 银双金属结构（Cu - Ag BS）修饰玻碳电极。然后，在KYNA分析物存在的情况下，将3,4 - 乙烯二氧噻吩（EDOT）单体在Cu - Ag BS/GCE上进行电聚合。通过场发射扫描电子显微镜（FESEM）、原子力显微镜（AFM）、X射线光电子能谱（XPS）、差分脉冲伏安法（DPV）、电化学阻抗谱（EIS）和循环伏安法（CV）对所制备的传感器进行表征。优化了电沉积参数。首次提出的MIP传感器能够在1.0 fM - 500 nM的宽线性范围内检测KYNA，检测限（LOD）为0.278 fM。此外，MIP层通过形成KYNA特异性识别腔提供高度选择性结合。值得注意的是，该传感器已在包括胎牛血清和人血清在内的复杂生物介质中成功验证，获得了高回收率值。所提出的传感器可能在未来用于神经退行性疾病早期诊断的诊断试剂盒设计中发挥作用。
