Shakeela Bibi, Chenyang Li, Salina Y Saddick, Lulu Xu, Yufeng Wang, Hao Zhang, Muhammad Awais, Iskander Tlili, Junfeng Wu, Jiandong Hu
Nitrogen-doped carbon quantum dots (N-CQDs) have emerged as a versatile platform for antibiotic biosensing, yet the field has been hindered by empirical optimization without mechanistic understanding. This review establishes quantitative structure-property-performance relationships that enable rational sensor design. We demonstrate that surface chemistry tuning, specifically the density of carboxylic acid groups and the ratio of carboxylic acid to amino functionalities, governs tetracycline binding affinity, while nitrogen doping levels and their distribution among pyridinic, pyrrolic, and graphitic configurations determine the dominant charge transfer pathways. Pyridinic N is identified as an important contributor to photoinduced electron transfer, showing a reported correlation with Stern-Volmer constants (R 2 = 0.89) across available N-CQD systems; however, further validation using expanded datasets and statistical approaches is required to establish predictive QSPR relationships, while graphitic N facilitates electrochemical charge transport. The interplay between static quenching, dynamic quenching, and inner filter effects is systematically deconvoluted, revealing that 65-85% of the fluorescence response in optimized sensors arises from ground-state complex formation. Surface engineering strategies including heteroatom co-doping, aptamer functionalization, and metal-organic framework hybridization extend sensor capabilities to complex matrices, achieving recovery rates of 84-98% in milk, soil, and wastewater. Unifying mechanistic understanding with quantitative design principles, this review provides a roadmap for translating N-CQD-based sensors from laboratory demonstrations to deployable tools for food safety monitoring, environmental surveillance, and therapeutic drug management.