Electrochemical-Enhanced\nCharge State Modulation of\nNitrogen-Vacancy Centers for Ultrasensitive Biodetection of MicroRNA-155

Sensitive and accurate miRNA detection\nis important in\ncancer diagnosis\nbut remains challenging owing to the essential features of miRNAs,\nsuch as their small size, high homology, and low abundance. This work\nproposes a novel electrochemical (EC)-enhanced quantum sensor achieving\nquantitative detection of miRNA-155 with simultaneous EC sensing.\nSpecifically, fluorescent nanodiamonds/MXene nanocomposites were synthesized\nand modified with dual-mode signal labels, enabling miRNA-155 concentration\nmeasurement via <i>T</i><sub>1</sub> relaxation time of\nnitrogen-vacancy (NV) centers and EC signals. Quantum sensing was\nenhanced via external voltage during the EC process, which modulated\nthe negatively charged state of the NV centers, thereby improving\nthe sensitivity and accuracy of miRNA-155 detection. EC sensing improved\nthe accuracy and reliability of miRNA-155 detection while enhancing\nquantum sensing. The limit of detection (LOD) of the EC-enhanced quantum\nbiosensor reached 10.0 aM, nearly 10<sup>6</sup> and 10 times lower\nthan the reported LODs of a quantum sensor using bulk diamond and\nfluorescent sensors, respectively. The LOD of EC sensing was 2.6 aM,\naligning with previous reports. The findings of the study indicated\nthat quantum sensing combined with EC sensing can achieve ultrasensitive\nmiRNA-155 detection with high accuracy and reliability, providing\nan advanced approach for early cancer diagnosis.