Triple-enhanced surface plasmon resonance spectroscopy based on cell membrane and folic acid functionalized gold nanoparticles for dual-selective circulating tumor cell sensing

Abstract Circulating tumor cells (CTCs) are an important biomarker of cancer and are valuable in evaluating the risk of metastatic progression and in facilitating precise therapeutic treatments. In this paper, a dual-selective strategy was constructed to achieve the sensitive detection of CTCs. Cell membrane fragment-functionalized AuNPs (M-AuNPs) and folic acid-functionalized AuNPs (FA-AuNPs) were fabricated and characterized. CTCs membrane containing the specific junction plakoglobin (JUP) could be captured onto Anti-JUP-modified gold chip selectively. FA-AuNPs can bind with M-AuNPs through the overexpressed FA receptors in the CTCs membrane. These double selective recognitions through the specific interaction between JUP and Anti-JUP, FA and FA receptor can ensure the sensor’s accuracy and specificity. The ultra-sensitive CTCs detection was achieved through multi-signal amplifications, including cell membrane fragments, M-AuNPs and FA-AuNPs. The biosensor constructed here has a low detection limit of 1 cell within the linear range of 101–105 cell mL-1. The low detection limit is in accordance with clinical detection standards. Owing to its outstanding selectivity, sensitivity, and stability, this new biosensor strategy for detecting CTCs offers new possibilities for clinical testing.