<p> A&#xa0;novel electrochemical cytosensor was developed&#xa0;with a three-protein recognition strategy, employing branched Pt Au nanospheres (B-Pt-Au NPs) as tags and MnO<sub>2</sub>-GO-Au nanosheet-modified electrodes for circulating tumor cells&#xa0;(CTC) detection. This system integrates specific magnetic separation and CTC enrichment with sensitive electrochemical detection to identify rare&#xa0;A549 cells in whole blood. MnO<sub>2</sub>-GO-Au nanosheets, known for their high conductivity and biocompatibility, were used to modify a bare electrode, improving the electrochemical interface for biomolecules. The B-Pt-Au NPs could only approach the sensing interface and enhance the current signal through their specific electrocatalytic activity when all three specific&#xa0;proteins, i.e. mucin 1 (MUC1), epithelial cell adhesion molecule (EpCAM), and epidermal growth factor receptor (EGFR),&#xa0;of&#xa0;rare A549 cells in peripheral&#xa0;blood were simultaneously expressed on the cell membrane. The developed cytosensor demonstrated a detection limit as low as 1 cell mL⁻<sup>1</sup> and, more importantly, could accurately distinguish A549 cells from other cancer cells. Thus, this proposed strategy offers a powerful tool for liquid biopsy analysis of extremely rare CTCs in complex peripheral blood, with potential applications in reliable early diagnosis of non-small cell lung cancer&#xa0;(NSCLC).</p> Graphical Abstract <p></p>

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A three-site recognition cytosensor for accurate detection of circulating tumor cells based on novel branched Pt Au nanospheres and MnO2-GO-Au nanosheets

  • Linzhi Xie,
  • Linxin He,
  • Yang Fu,
  • Yuxin Wei,
  • Kun Zhang,
  • Mei Chen

摘要

A novel electrochemical cytosensor was developed with a three-protein recognition strategy, employing branched Pt Au nanospheres (B-Pt-Au NPs) as tags and MnO2-GO-Au nanosheet-modified electrodes for circulating tumor cells (CTC) detection. This system integrates specific magnetic separation and CTC enrichment with sensitive electrochemical detection to identify rare A549 cells in whole blood. MnO2-GO-Au nanosheets, known for their high conductivity and biocompatibility, were used to modify a bare electrode, improving the electrochemical interface for biomolecules. The B-Pt-Au NPs could only approach the sensing interface and enhance the current signal through their specific electrocatalytic activity when all three specific proteins, i.e. mucin 1 (MUC1), epithelial cell adhesion molecule (EpCAM), and epidermal growth factor receptor (EGFR), of rare A549 cells in peripheral blood were simultaneously expressed on the cell membrane. The developed cytosensor demonstrated a detection limit as low as 1 cell mL⁻1 and, more importantly, could accurately distinguish A549 cells from other cancer cells. Thus, this proposed strategy offers a powerful tool for liquid biopsy analysis of extremely rare CTCs in complex peripheral blood, with potential applications in reliable early diagnosis of non-small cell lung cancer (NSCLC).

Graphical Abstract