Area-selective assembly of cell membrane/Ti₃C₂T_x MXene nanocomposites for biomimetic electrochemical detection

Cell membrane (CM) coating technology offers a promising strategy for developing biomimetic electronics, leveraging native cellular functionalities such as antifouling properties and receptor-mediated specificity. However, achieving uniform and stable CM deposition within precisely defined regions remains a significant challenge. Here, we present an area-selective CM coating approach that confines A549 lung carcinoma cells-derived membranes (AM) to photolithographically defined Ti₃C₂T_x MXene micropatterns. The hydrophilic surface of Ti₃C₂T_x, enriched with hydroxyl groups, promotes strong electrostatic interactions with the phospholipid headgroups, enabling the formation of a uniform and continuous MXene-directed CM coating. Fluorescence microscopy shows that AM coatings on MXene films effectively suppress nonspecific protein adsorption while preserving highly specific, receptor-mediated binding of SARS-CoV-2 from clinical samples via endogenous angiotensin-converting enzyme 2 (ACE2) receptors. Based on these features, we further integrated this biomimetic interface into an electrochemical biosensor by confining the MXene and AM layers to the working electrode. The AM-coated sensors exhibited excellent sensitivity for the S1 subunit of the SARS-CoV-2 spike protein, achieving a detection limit of 132 pM with high selectivity against various interfering molecules. Furthermore, the AM-on-MXene sensor successfully discriminated SARS-CoV-2 positive clinical samples from healthy controls, highlighting its clinical applicability. These results demonstrate a robust and scalable strategy for integrating biological membranes with 2D conductive nanomaterials, significantly broadening the potential of biointerface engineering in advanced bioelectronics.