Recently, the research team led by Professor WANG Hongzhi from the Institute of Health and Medical Technology, the Hefei Institute of Physical Science of the Chinese Academy of Sciences, successfully developed a dual-functional sensor chip, PlasmoBridge, which bridges plasmonic nanoparticles using aptamer molecules.
This innovative chip enables ultrasensitive, highly specific, and reproducible detection of Methotrexate (MTX) in serum, providing a new and feasible strategy for rapid therapeutic drug monitoring (TDM) in clinical settings.
The related study was published in Biosensors and Bioelectronics.
MTX is a common chemotherapeutic agent with a narrow therapeutic window and high variability among patients, making real-time blood concentration monitoring crucial for safe and effective treatment. However, traditional methods such as LC-MS/MS and immunoassays, though accurate, are often costly, time-consuming, and prone to cross-reactivity.
To address these challenges, the team designed the PlasmoBridge chip by linking silver nanoparticles with aptamer molecules, forming a stable plasmonic nanobridge. This structure combines enhanced molecular signal amplification with selective molecular recognition of MTX. When serum samples are applied, the aptamer captures MTX molecules into the "hotspot" region, producing strong surface-enhanced Raman scattering (SERS) signals for highly sensitive and specific detection.
The chip achieved a limit of detection (LOD) as low as 4.64×10⁻⁸ M for MTX in serum. With a convolutional neural network (CNN) for spectral analysis, the team established a quantitative model with excellent linearity (R² > 0.99) over the range of 1×10⁻⁷ M to 1×10⁻⁴ M.
In a preclinical osteosarcoma mouse model, the PlasmoBridge platform was used to dynamically monitor serum MTX levels and adjust doses in real time with the CNN model. This AI-assisted, TDM-guided dosing maintained antitumor efficacy while significantly reducing MTX-induced liver, kidney, and intestinal toxicity, demonstrating its safety and translational potential for precision medicine.
The "aptamer-nanobridge" strategy introduced in this study enables stable plasmonic hotspot regulation and targeted molecular enrichment. By integrating high sensitivity, rapid detection, and operational simplicity, the approach provides a promising tool for personalized MTX monitoring and broader clinical applications in precision therapeutics.
PlasmoBridge: An aptamer–nanoparticle dual-assembly structure that forms stable plasmonic hotspots, enabling the capture and rapid ultrasensitive detection of methotrexate in serum. (Image by HUANG Guangyao)