Triggerable H2O2-Cleavable Switch of Paper-Based Biochips Endows Precision of Chemometer/Ratiometric Electrochemical Quantification of Analyte in High-Efficiency Point-of-Care Testing.

In this work, a triggerable H2O2-cleavable fluid switch mediated paper-based biochip, being amenable to multiplexing and quantitative analysis with the dual-response output of visual screening and ratiometric electrochemistry, was developed for sensitive detection of target on-site. By properly implanting hydrophobic Ag-H2O2 responsive material in specific zone to form a programmable fluid switch, the biochip could achieve different modes of blocking/connecting switching automatically. In order to improve the test performance, a ratiometric electrochemical signal readout was designed, which was enhanced by a secondary in situ growth method fabricating trepang-shaped Au modified paper working electrode. In virtue of hybridization chain reaction, classic competitive recognition interactions of aptamer and target, and ratiometric internally calibrated mechanisms, ultrasensitive detection of the target was realized. To acquire a more quantitative and straightforward naked eye visual screening, the hydrophobic Ag switch was triggered by stimulating instructions from H2O2, thus reconnecting the electrochemical and ratiometric units automatically and resulting in a "signal on" visual fluidic flow on the chemometer characterized by the accurate distance of color development as a detection motif. With MCF-7 and K562 cells as models, wider linear detection ranges from 150 to 1.0 × 107 and 220 to 7.0 × 106 cells mL-1 for MCF-7 and K562 cells, respectively, were achieved. Meanwhile, thanks to the paper fluid chemometer, an acceptable screening detection limit of 103 cells mL-1 was obtained in the quantitative colorimetric assays. The proposed paper-based biochips opened up new horizons for designing of integratable, easy-to-use, and precise point-of-care testing devices.