A label-free impedimetric cytosensor based on galactosylated gold-nanoisland biointerfaces for the detection of liver cancer cells in whole blood

•A label-free and ultrasensitive EIS cytosensor was developed to detect CTCs.•The viable HepG-2 cells were captured to the senor by a multivalent Gal-ASGP-R binding.•The nanostructured GNI has an enhanced electro-transfer rate and a low LOD of 30 cell mL− 1.•The EIS biosensor has a good reproducibility with the RSD of 1.9% in blood samples.•It provides a versatile and noninvasive sensing platform for early diagnosis of tumor.

Circulating tumor cells (CTCs), as potential cancer biomarkers, play a crucial role in cancer diagnosis, prognosis and treatment. However, there are still significant challenges due to their rarity. In this paper, a label-free and ultrasensitive electrochemical impedance cytosensor was developed by a galactosylated gold-nanoisland (Gal-GNI) biointerface for the capture and detection of rare cancer cells (HepG-2) in whole blood samples. By mimic the natural multivalent biorecognition systems, the biointerface was designed to capture the target cancer cells by the specific binding between galactosyl ligands of Gal-GNI and over-expressed asialoglycoprotein receptors (ASGP-R) on the surface of HepG-2. From the results of electrochemical impedance spectroscopy (EIS) and fluorescence spectroscopy, the nanostructured Gal-GNI provides an improved electron-transfer rate, specific detection for HepG-2, and good biocompatibility for viable captured cells. The capture of HepG-2 to the EIS cytosensor increased the electron-transfer resistance, with a good correlation with the logarithm of the concentration from 1.0 × 102 to 1.0 × 105 cells mL− 1, with a low detection limit of 30 cells mL− 1. This cytosensing strategy has good reproducibility with the RSD of 1.9% in blood samples, indicating that it can be used as a potential noninvasive assay tool for the early diagnosis and therapy of tumor.

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