Point-of-care testing of protein biomarkers by integrating a personal glucose meter with a concatenated DNA amplifier

Abstract Considering most clinical biomarkers and therapeutic targets are proteins, developing point-of-care testing (POCT) of protein biomarkers will be not only greatly beneficial to patients, but also helpful for promoting medical development. In this work, we have proposed a versatile biosensor for the POCT of protein disease biomarkers by integrating the most technology-matured POCT device, i.e., personal glucose meter (PGM) with a concatenated DNA amplifier. In order to convert protein targets into cascaded glucose production, the concatenated DNA amplifier is fabricated by a catalytic hairpin assembly (CHA) reaction and a hybridization chain reaction (HCR), which is simplified as CHA-HCR system. As a “plug-and-play” converter and amplifier, the integrated CHA-HCR system can be immediately initiated by the detected protein target, resulting in dynamic DNA assembly-directed invertase polymerization on Au-Fe3O4 nanoparticles for cascaded glucose production. With the advantages of programmable conversion strategy, high conversion efficacy, anti-interference, specificity, and sensitivity, the capability of this system has been demonstrated by the quantification of several protein biomarkers in serum, including anti-digoxin antibody, thrombin, and anti-HCV antibody. Therefore, it can provide a universal and rational toolbox to develop more POCT device-based biosensors for the detection of disease-related biomarkers other than glucose in complex matrices.