基于荧光聚离子复合胶束传感器阵列的奥兹海默症诊断研究

Alzheimer's disease is an insidious neurodegenerative disease. Early diagnoses of Alzheimer's disease can be realized through monitoring protein-based biomarkers in physiological environment. The current sensing system for Alzheimer's biomarkers are always designed specially according to an Alzheimer's biomarker. The highly selective sensing system involves in complicated synthetic procedures and behaves badly in diagnostic accuracy. In order to improve the situation, this project intends to apply the polyion complex micelles (PICs) self-assembled by block polyions and carbon dots (CDs) to construct sensor array. Multiple Alzheimer's biomarkers can be simultaneously monitored by using the sensor array. The sensor array based on PICs applies the elaborate and tailorable chemical structure of polymers to regulate the photoluminescent and surficial property of CDs, which will further affect the interaction between the CDs and Alzheimer's biomarkers. The finger-print patterns of various Alzheimer's biomarkers can be plotted using the PICs-based sensor array. Crucial biomarkers can be screened through principal component analysis. A precise diagnosis of Alzheimer's can be made through monitoring the concentration of multiple crucial biomarkers. The sensing system makes full use of the good biocompatibility, stable nanostructure and electrostatic enrichment ability of PICs, which improves the sensitivity and stability of array analysis. The sensor array based on the fluorescent PICs is simple to prepare and easy to operate with high sensitivity and stability, which will show significant research value and broad application prospects in the early clinical diagnoses of Alzheimer's disease.

奥兹海默症，又称老年痴呆症，是一种起病隐匿的神经系统退行性疾病。生物标志物检测可以对奥兹海默症进行早期诊断，但现有的检测方法不仅构建过程复杂，而且只能跟踪某一种生物标志物，诊断准确率不高。针对该问题，本项目选取由嵌段聚电解质和荧光碳点自组装形成的聚离子复合胶束作为传感单元组建传感器阵列，利用聚合物丰富的化学结构调节碳点的荧光性能、表面化学结构及其与生物标志物相互作用的情况，从而绘制不同生物标志物的特征指纹图谱，通过主成分分析筛选出起关键作用的多种生物标志物，根据关键生物标志物的浓度水平对奥兹海默症进行准确的诊断。该传感系统充分利用了聚离子复合胶束良好的生物相容性、稳定的纳米结构和静电富集能力，有效提高了阵列分析的稳定性和灵敏度。基于荧光聚离子复合胶束的传感器阵列制备简单、操作方便，检测系统灵敏度高、稳定性强，在奥兹海默症临床诊断领域具有重要的研究价值和广阔的应用前景。

发展简单、快速、灵敏、准确的奥兹海默症早期诊断方法，对于奥兹海默症的预防、治疗和新药开发具有重要的意义。本项目根据哺乳动物嗅觉系统的传感机理，利用荧光碳量子点（简称碳点）和嵌段聚电解质自组装形成的聚离子复合胶束（简称PIC胶束）作为传感单元，构建传感器阵列分析系统，应用于奥兹海默症的早期诊断。为了寻找适合构建PIC胶束的碳点，我们采用柠檬酸、尿素、甲酰胺、氨基酸、海藻酸钠等带有电荷的碳源作为原材料，通过微波法和水热法制备表面带有电荷的碳点。通过优化反应体系组成、反应时间等条件，控制碳点的尺寸、粒径分布以及溶液稳定性，调整碳点的光致发光性能。利用透射电子显微镜、红外光谱、X射线光电子能谱等多种表征手段分析碳点的化学结构。通过可控聚合的方法制备一系列不同聚合度和分子量分布的嵌段聚电解质（聚乙二醇-b-聚丙烯酸等）。以PIC胶束为传感单元组建传感器阵列，通过收集、分析传感单元与分析物相互作用前后差异性的荧光强度，绘制Aβ蛋白、Aβ寡聚物和Aβ淀粉样纤维的特征性指纹图谱。通过对不同聚集状态Aβ蛋白的检测与识别，实现了不同阶段奥兹海默症的诊断。通过优化碳点/聚合物的种类、组成、比例等相关参数，调节传感单元的尺寸、稳定性、带电量以及荧光发射能力，提高了传感器阵列的稳定性和灵敏度。此外，应用碳点传感器阵列，我们还实现了对于小分子（氨基酸、有机酸、生物胺）、大分子（蛋白质）、复杂系统（烟草）的分析检测，以及其他疾病模型（肿瘤、贫血病）的诊断评估。在本项目中，我们还将碳点的应用拓展到能源催化、生物矿化、疾病治疗等多个方向。