Combination of Magnetic-Beads-Based Multiple Metal Nanoparticles Labeling with Hybridization Chain Reaction Amplification for Simultaneous Detection of Multiple Cancer Cells with Inductively Coupled Plasma Mass Spectrometry.

The high-throughput and rapid screening of cancer cells in blood is one of the most effective ways to realize clinical early diagnosis of cancer. We herein developed an inductively coupled plasma mass-spectrometry (ICP-MS)-based method for simultaneously counting two cancer cells, human hepatocellular carcinoma cell (SMMC-7721) and human lung carcinoma cell (A549), with high sensitivity and specificity. The method employed a magnetic-beads (MBs)-based dual aptamers-dual metal nanoparticles labeling technique for simultaneously recognizing and labeling different metal nanoparticles (AuNPs and AgNPs) on SMMC-7721 and A549 cancer cells, respectively, to generate ICP-MS signals, and a DNA hybridization chain reaction strategy for realizing "one SMMC-7721 cell-to-massive AuNPs" and "one A549 cell-to-massive AgNPs" amplification effect to improve sensitivity. The employment of ICP-MS detection and MBs not only simplified the experimental operation but also greatly enhanced the resistance of the method to the complicated matrix. The method can be used to simultaneously detect as few as 50 SMMC-7721 and A549 cancer cells in serum within 1 h with a recovery of 93-108% and a relative standard deviation (RSD, n = 5) < 5%. The method has notable advantages such as high sensitivity, excellent stability, high throughput, shorter analysis time, and strong resistibility to the complex matrix. Especially, the method can also be used to detect various cancer cells via altering aptamers and designing appropriate link/signal probes according to the target cells. The success of this study offers a potential approach for the high-throughput and rapid screening of cancer cells in clinical early diagnosis of cancer.