Direct Charge-Transfer Chemosensing Materials for Painless Multimodal Disease Diagnosis

Conspectus Multimode biosensing platforms represent a promising approach in painless diagnostics, integrating electrochemical and conductivity-based sensing modalities through direct charge-transfer mechanisms. These systems address critical limitations of conventional single-mode detection by providing cross-validated biomarker measurements with enhanced reliability in complex physiological environments. This account presents a systematic framework for the rational design and performance optimization of these advanced sensing platforms. The foundation of multimodal biosensing lies in direct charge-transfer materials that enable primarily mediator-free electron exchange with target analytes. We first elucidate the distinct chemosensing mechanisms of typical MXenes and metal–organic frameworks (MOFs) systems. The working mechanisms of MXenes and MOFs demonstrate distinct yet complementary approaches to direct electron-transfer detection. MXenes utilize metallic conductivity and surface redox sites for rapid electrochemical detection, while MOFs leverage porous coordination networks for selective but slower analyte recognition. MXenes achieve high sensitivity but face oxidation issues, whereas MOFs offer molecular sieving yet suffer from low conductivity. These limits give emphasis to the studies on advanced engineering designs to enhance stability and performance for practical biosensing applications. We mainly present three advanced material systems that enable multimodal biomarker detection: MOF with tunable charge-transfer sites, MXene nanosheets with excellent charge-transfer capacity, biomimetic MOF/MXene composites for synergistic electron transfer, and some other effective charge-transfer chemosensing materials (including transition metal dichalcogenides, black phosphorus (BP), and graphite-like carbon nitride). Additionally, the promising potential of these advanced material innovations is demonstrated across multiple clinical applications, offering groundbreaking solutions for real-time asthma monitoring, precision management of periodontal disease, and enhanced wound healing. Referring to asthma monitoring, we have developed a great Pt single-atom sensitized Nb 2 CT x nanosheet/TPU composite (Pt SA-Nb 2 CT x @TPU) that achieved interference-free asthma monitoring through its innovative dual-mode sensing mechanism for reliable asthma diagnosis. In terms of periodontitis, our dual-modal periodontitis sensor addressed diagnostic challenges by synergizing gas-sensing (respiratory biomarkers) and strain/pressure-sensing (maxillofacial movements). For wound healing, the MN-TENG integrated system represented a key development in painless biomedical technology, seamlessly combining diagnostic and therapeutic functions to transform chronic wound management. Finally, we conclude by addressing remaining challenges in signal decoupling, long-term stability, and clinical validation, while outlining emerging opportunities in AI-powered dynamic calibration, closed-loop therapeutic systems, and minimally invasive implantable sensor arrays. Through this comprehensive analysis, we provide both fundamental insights into charge-transfer mechanisms and practical guidelines for developing next-generation intelligent monitoring systems, bridging the gap between laboratory innovation and clinical implementation in precision medicine. The integration of these technologies promises to revolutionize healthcare by enabling continuous, multimodal biomarker monitoring with unprecedented accuracy and reliability.