Abstract：
An innovative and universal imprinted sensor design for sandwich type detection of gemcitabine (GMT) in human serum samples is described. GMT is widely used in the treatment of different tumors, such as lung, ovarian, pancreatic, and breast cancer. The serum albumin-drug interaction was translated to design a multifunctional, ratiometric and dual mode silver nanoparticle based probe (BSA-Ag nanoprobe), as a read out system. Subsequently, polypyrrol imprinted drug receptor sites was engineered to selectively capture the GMT on the transducer surface. The GMT was sandwiched between imprinted receptor surface and BSA-Ag nanoprobe to generate the spectro-electrochemical signals. The formation of nanoprobe was confirmed through various characterization techniques, including X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, micro-Raman spectroscopy, Dynamic light scattering (DLS), and UV-Visible (UV-Vis) analysis, while each step of sensor fabrication was characterized via field emission scanning electron microscope (FE-SEM), Static water Contact angle measurements, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Different variable parameters were optimized to improve the analytical performance of the sensor design. Under optimal conditions, spectro-electrochemical sensor permitted linear ranges between 1 and 200 μmol L-1 and 0.5-200 μmol L-1, with limits of detection (LOD) of 0.4 μmol L-1 and 0.15 μmol L-1 respectively. Furthermore, the designed sensor successfully differentiated the serum samples of lung cancer patients and healthy volunteers. The obtained results were validated with standard Liquid chromatography-mass spectrometry (LC/MS) analysis of the patients and healthy volunteer\'s serum samples. Lastly, density functional theory (DFT) and molecular docking calculations revealed the enhanced GMT binding capability of molecularly imprinted polypyrrole and molecular level interaction between the GMT and BSA, to validate the sandwich sensor design.
摘要：
描述了一种创新的通用印迹传感器设计，用于夹心式检测人血清样品中吉西他滨（GMT）。GMT广泛应用于不同肿瘤的治疗,比如肺，卵巢,胰腺,和乳腺癌。血清白蛋白-药物相互作用被转化为设计一种多功能的，基于比率和双模银纳米粒子的探针（BSA-Ag纳米探针），作为一个读出系统。随后，设计了聚吡咯印迹药物受体位点以选择性捕获换能器表面的GMT。将GMT夹在印迹受体表面和BSA-Ag纳米探针之间以产生光谱电化学信号。通过各种表征技术证实了纳米探针的形成，包括X射线衍射(XRD)，傅里叶变换红外(FTIR)光谱,显微拉曼光谱,动态光散射(DLS),和紫外可见(UV-Vis)分析，而传感器制造的每个步骤都是通过场发射扫描电子显微镜(FE-SEM)表征的，静态水接触角测量，循环伏安法（CV），和电化学阻抗谱(EIS)。优化了不同的可变参数，以提高传感器设计的分析性能。在最优条件下,光谱电化学传感器允许线性范围在1至200μmolL-1和0.5-200μmolL-1之间，检测限（LOD）分别为0.4μmolL-1和0.15μmolL-1。此外，设计的传感器成功地区分了肺癌患者和健康志愿者的血清样本。所获得的结果通过对患者和健康志愿者血清样品的标准液相色谱-质谱(LC/MS)分析进行验证。最后,密度泛函理论(DFT)和分子对接计算揭示了分子印迹聚吡咯的GMT结合能力增强,来验证三明治传感器的设计。
