A novel high-sensitivity electrochemical sensor for cancer cell detection by means of phosphorene functionalized with sialic acid biomolecules

As recently discovered, sialic acid (SA) plays a crucial role in cell functioning and malignant transformation, and its interaction with malignant cells could be a key parameter in smart and label-free drug delivery. In this work, we functionalized phosphorene with SA molecules and studied its superior interaction with breast cancer cell lines. The formation of phosphorene is feasible via hydrogen plasma treatment and the conversion of amorphous phosphorus into highly crystalline nanosheets. The exposure of highly metastatic breast cancer cell lines to functionalized electrodes leads to significantly improved attachment of cells to the surface of the electrode, leading to superior electrical signals. These activated sheets can act as media for the attachment and capture of cancerous cells and show detectable electrochemical signals with a record value of 4 cells per mL. Although this sensor presents great detection ability, its performance on healthy or less aggressive and noninvasive cells is surprising. This is believed to be due to the presence of SA-binding immunoglobulin superfamily lectins (Siglecs) on the membrane of invasive cancer cells as opposed to their non-malignant or less invasive counterparts. Apart from the experimental work, we investigated the attachment of SA molecules onto the surface of phosphorene using density functional theory (DFT), corroborating the formation of covalent bonds between the carboxylic component of the molecule and the lone pair of electrons of phosphorus atoms.