Cell‐sensing Analogue Nanopore for Rapid Detection of Protein‐Related Targets

Nanopores offer significant advantages in biosensing. Conventional nanopore sensors require probe modification within the pore, and there are two major obstacles: inhomogeneity of probe modification within the pore, and distortion of the detection signal due to the uncontrollable dynamics of the target within the pore. Here, we constructed a cell-sensing analogue nanopore (CeSa-nanopore), by coating the outer surface of the nanopore with cell membrane. The inhomogeneity of probe modification and the uncontrollable kinetics of target-probe binding were also addressed. Specific cells are selected to prepare CeSa-nanopore, for example, cells with high expression of angiotensin-converting enzyme 2 (ACE2) are used to achieve the detection of SARS-CoV-2. When SARS-CoV-2 binds to CeSa-nanopore the surface potential changes, causing a change in the ionic current, thus enabling its detection with a detection rate of 100%. In addition, the detection of different proteins, such as follicle-stimulating hormone (FSH), can be achieved by changing the cell membrane coating. The identification of cancer cells in ascites can also be achieved by utilizing homologous targeting between cancer cells. Importantly, the use of CeSa-nanopores for the detection of these targets eliminates the need for pre-processing and significantly reduces detection time.