Addressable TiO₂ Nanotubes Functionalized Paper-Based Cyto-Sensor with Photocontrollable Switch for Highly-Efficient Evaluating Surface Protein Expressions of Cancer Cells

Inspired by the well-known “Wheel of Fortune”, a rotatable paper-photocontrollable switch (RPPS) was designed to form an addressable paper-based photoelectrochemical (PEC) cyto-sensor for ultrasensitive detection of a cell-surface protein. By simply rotating the RPPS, a light source can selectively activate the desired working zones of the cyto-sensor. To realize the high-performance paper-based PEC cyto-sensor, a cascaded photoactive interface consisting of neat TiO2 nanotubes arrays, Pt nanoparticles (NPs), and nitrogen–carbon dots was introduced into paper fibers, gaining signal-on PEC state (NTPP for short). Then the NTPP fixed with a hairpin probe H1 allowed the hybridization chain reaction (HCR) to happen with CuS NPs-labeled hairpin probe H2 by the free primer strand (PS) triggering; hence, the CuS NPs as the emulative sensitizers were introduced onto the NTPP with the photocurrent intensity decrement for signal-off PEC state. During this process, the PS carefully designed with specific sequences can recognize the target strand (TS) of MCF-7 cells and stimulate HCR by its trigger zone. The presence of MCF-7 cells destroyed the interaction between PS and ZnFe2O4 functionalized TS, causing the PS release from the mixture of PS and TS under the help of a magnet. Then, the released PS, acting as a primer probe, realized ultrasensitive detection of a cell-surface protein. On the basis of this novel protocol, multiple-signal amplification was skillfully imported into the addressable paper PEC chip, resulting in ultrasensitive quantification of carcinoembryonic antigen in the surface of MCF-7 cells. Given the fascinating analytical performances of the developed cyto-sensor, ultralow expression of antigens for MCF-7, A549, and PC 3 cells was discriminated effectively