Sridev Janani, Deen Arif R, Ali Md Younus, Ting Wei-Ting, Deen M Jamal, Howlader Matiar M R
Department of Electrical and Computer Engineering, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Department of Integrated Biomedical Engineering and Health Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Biosensors (Basel). 2025 Sep 19;15(9):626. doi: 10.3390/bios15090626.
Tryptophan (Trp) and tryptamine (Tryp), critical biomarkers in mood regulation, immune function, and metabolic homeostasis, are increasingly recognized for their roles in both oral and systemic pathologies, including neurodegenerative disorders, cancers, and inflammatory conditions. Their rapid, sensitive detection in biofluids such as saliva-a non-invasive, real-time diagnostic medium-offers transformative potential for early disease identification and personalized health monitoring. This review synthesizes advancements in electrochemical sensor technologies tailored for Trp and Tryp quantification, emphasizing their clinical relevance in diagnosing conditions like oral squamous cell carcinoma (OSCC), Alzheimer's disease (AD), and breast cancer, where dysregulated Trp metabolism reflects immune dysfunction or tumor progression. Electrochemical platforms have overcome the limitations of conventional techniques (e.g., enzyme-linked immunosorbent assays (ELISA) and mass spectrometry) by integrating innovative nanomaterials and smart engineering strategies. Carbon-based architectures, such as graphene (Gr) and carbon nanotubes (CNTs) functionalized with metal nanoparticles (Ni and Co) or nitrogen dopants, amplify electron transfer kinetics and catalytic activity, achieving sub-nanomolar detection limits. Synergies between doping and advanced functionalization-via aptamers (Apt), molecularly imprinted polymers (MIPs), or metal-oxide hybrids-impart exceptional selectivity, enabling the precise discrimination of Trp and Tryp in complex matrices like saliva. Mechanistically, redox reactions at the indole ring are optimized through tailored electrode interfaces, which enhance reaction kinetics and stability over repeated cycles. Translational strides include 3D-printed microfluidics and wearable sensors for continuous intraoral health surveillance, demonstrating clinical utility in detecting elevated Trp levels in OSCC and breast cancer. These platforms align with point-of-care (POC) needs through rapid response times, minimal fouling, and compatibility with scalable fabrication. However, challenges persist in standardizing saliva collection, mitigating matrix interference, and validating biomarkers across diverse populations. Emerging solutions, such as AI-driven analytics and antifouling coatings, coupled with interdisciplinary efforts to refine device integration and manufacturing, are critical to bridging these gaps. By harmonizing material innovation with clinical insights, electrochemical sensors promise to revolutionize precision medicine, offering cost-effective, real-time diagnostics for both localized oral pathologies and systemic diseases. As the field advances, addressing stability and scalability barriers will unlock the full potential of these technologies, transforming them into indispensable tools for early intervention and tailored therapeutic monitoring in global healthcare.
色氨酸（Trp）和色胺（Tryp）是情绪调节、免疫功能和代谢稳态中的关键生物标志物，它们在口腔和全身疾病（包括神经退行性疾病、癌症和炎症性疾病）中的作用日益受到认可。在唾液等生物流体中对它们进行快速、灵敏的检测——唾液是一种非侵入性的实时诊断介质——为早期疾病识别和个性化健康监测提供了变革性潜力。本综述综合了为Trp和Tryp定量量身定制的电化学传感器技术的进展，强调了它们在诊断口腔鳞状细胞癌（OSCC）、阿尔茨海默病（AD）和乳腺癌等疾病中的临床相关性，在这些疾病中，Trp代谢失调反映了免疫功能障碍或肿瘤进展。电化学平台通过整合创新的纳米材料和智能工程策略，克服了传统技术（如酶联免疫吸附测定法（ELISA）和质谱法）的局限性。基于碳的结构，如用金属纳米颗粒（Ni和Co）或氮掺杂剂功能化的石墨烯（Gr）和碳纳米管（CNTs），放大了电子转移动力学和催化活性，实现了亚纳摩尔级的检测限。通过适配体（Apt）、分子印迹聚合物（MIP）或金属氧化物杂化物进行掺杂与先进功能化之间的协同作用赋予了卓越的选择性，能够在唾液等复杂基质中精确区分Trp和Tryp。从机理上讲，通过定制的电极界面优化了吲哚环处的氧化还原反应，从而在重复循环中提高了反应动力学和稳定性。转化方面的进展包括用于连续口腔内健康监测的3D打印微流体和可穿戴传感器，证明了其在检测OSCC和乳腺癌中升高的Trp水平方面的临床实用性。这些平台通过快速响应时间、最小污染以及与可扩展制造的兼容性满足了即时检测（POC）的需求。然而，在标准化唾液采集、减轻基质干扰以及在不同人群中验证生物标志物方面仍然存在挑战。新兴的解决方案，如人工智能驱动的分析和防污涂层，以及跨学科努力以优化设备集成和制造，对于弥合这些差距至关重要。通过将材料创新与临床见解相结合，电化学传感器有望彻底改变精准医学，为局部口腔疾病和全身性疾病提供经济高效的实时诊断。随着该领域的发展，解决稳定性和可扩展性障碍将释放这些技术的全部潜力，将它们转变为全球医疗保健中早期干预和定制治疗监测不可或缺的工具。
