Nanobiosensors for Leukemia Minimal Residual Disease Monitoring: A Review of Recent Advances and Translational...

Minimal residual disease (MRD) in leukemia is essential for evaluating treatment response, predicting relapse risk, and guiding individualized therapy. Conventional MRD assays, including multiparameter flow cytometry and quantitative polymerase chain reaction, generally achieve detection thresholds of approximately 10-4-10-6 under validated conditions. By contrast, representative nanobiosensor platforms have reported femtomolar or even sub-femtomolar limits of detection or rare-cell detection at very low concentrations in optimized model systems, indicating their potential advantages in signal amplification and low-abundance biomarker detection. This review summarizes recent advances in nanobiosensors for leukemia MRD monitoring, with emphasis on nanomaterial design, molecular recognition strategies, and signal transduction mechanisms. It further discusses their application to clinically relevant MRD markers, including circulating tumor DNA, circulating leukemic cells, fusion gene transcripts, abnormal proteins, and extracellular vesicles. Key translational challenges are also analyzed, including insufficient assay standardization, limited cross-platform comparability, matrix interference in complex biological samples, manufacturing scalability, cost control, biosafety, and regulatory evaluation. Finally, this review proposes a target-matrix-readout-translation framework for evaluating nanobiosensors in leukemia MRD monitoring, emphasizing not only analytical sensitivity but also biomarker relevance, clinical-sample validation, comparability with established assays, and regulatory readiness.