An integrated microfluidic cytosensor coupled with self-calibration electrochemical/colorimetric dual-signal output for sensitive and accurate detection of hepatoma cells

Hepatocellular carcinoma (HCC) is one of the highly prevalent and lethal malignancies around the world. As circulating tumor cells (CTCs) are regarded as critical indicators in the early diagnosis and prognosis of cancer, it is imperative to develop hepatoma cytosensor in liquid biopsy. Herein, this study introduces a microfluidic cytosensor for HepG2 cell detection, leveraging dual-site recognition and dual-mode signal readout to enhance specificity and accuracy. The cytosensor employs hyaluronic acid (HA) functionalized magnetic beads (MB-HA) and phenylboronic acid (PBA) modified iron metal organic framework (Fe-MOF-PBA) for magnetic isolation and signal labeling. Owing to the favorable peroxidase-mimic and electroactivity of Fe-MOF, the color of oxidized 3,3′,5,5′-tetramethylbenzidine (TMB) and the oxidation current of its amino-functionalized organic ligand were served as electrochemical/colorimetric (EC/CL) dual-signal for HepG2 quantification. This approach achieved a detection limit of 3 cells mL−1 (S/N = 3) and a broad linear range of 10–105 cells mL−1. Furthermore, the successful determination of HepG2 in clinical blood samples manifests the great prospect of the integrated microfluidic chip in precise, early point-of-care HCC diagnostics.