Single Nanoparticle Counting-Based Liquid Biopsy for Cancer Diagnosis

Liquid biopsy has become a sought-after technique for disease diagnosis because it provides real-time, dynamic, and comprehensive information that can alleviate the dilemmas faced by tissue biopsy. Multiplexed microRNAs (miRNAs) have been demonstrated to be promising biomarkers in liquid biopsy but fall short in providing simple and sensitive analytical methods. In this work, we established a novel nanoparticle counting strategy to accomplish simultaneous analysis of three breast cancer-associated miRNAs for breast cancer diagnosis. The frequency of nanoparticles not involved in the formation of sandwich structures was detected by single-particle inductively coupled plasma mass spectrometry (SP-ICPMS) to quantify the targets. The detection limits for miR-21, miR-155, and miR-16 were 49, 51, and 55 amol, respectively. The strategy was applied to clinical samples and successfully achieved the diagnosis between normal individuals and breast cancer patients. The area under the curve (AUC) for the combination of the relative expression of miR-21 and miR-155 was 0.818. The above results indicate that this strategy has potential and holds great promise for playing an essential role in cancer diagnosis.