Electrochemical-Enhanced Charge State Modulation of Nitrogen-Vacancy Centers for Ultrasensitive Biodetection of MicroRNA-155

Sensitive and accurate miRNA detection is important in cancer diagnosis but remains challenging owing to the essential features of miRNAs, such as their small size, high homology, and low abundance. This work proposes a novel electrochemical (EC)-enhanced quantum sensor achieving quantitative detection of miRNA-155 with simultaneous EC sensing. Specifically, fluorescent nanodiamonds/MXene nanocomposites were synthesized and modified with dual-mode signal labels, enabling miRNA-155 concentration measurement via T₁ relaxation time of nitrogen-vacancy (NV) centers and EC signals. Quantum sensing was enhanced via external voltage during the EC process, which modulated the negatively charged state of the NV centers, thereby improving the sensitivity and accuracy of miRNA-155 detection. EC sensing improved the accuracy and reliability of miRNA-155 detection while enhancing quantum sensing. The limit of detection (LOD) of the EC-enhanced quantum biosensor reached 10.0 aM, nearly 10⁶ and 10 times lower than the reported LODs of a quantum sensor using bulk diamond and fluorescent sensors, respectively. The LOD of EC sensing was 2.6 aM, aligning with previous reports. The findings of the study indicated that quantum sensing combined with EC sensing can achieve ultrasensitive miRNA-155 detection with high accuracy and reliability, providing an advanced approach for early cancer diagnosis.