Ultrasensitive and low-volume point-of-care diagnostics on flexible strips – a study with cardiac troponin biomarkers

Abstract

We demonstrate a flexible, mechanically stable, and disposable electrochemical sensor platform for monitoring cardiac troponins through the detection and quantification of cardiac Troponin-T (cTnT). We designed and fabricated nanostructured zinc oxide (ZnO) sensing electrodes on flexible porous polyimide substrates. We demonstrate ultrasensitive detection is capable at very low sample volumes due to the confinement phenomenon of target species within the ZnO nanostructures leading to enhancement of biomolecular binding on the sensor electrode surface. The performance of the ZnO nanostructured sensor electrode was evaluated against gold and nanotextured ZnO electrodes. The electrochemical sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for cTnT were immobilized on the sensor electrodes using thiol based chemistry. Detection of cTnT in phosphate buffered saline (PBS) and human serum (HS) buffers was achieved at low sample volumes of 20 μL using non-faradaic electrochemical impedance spectroscopy (EIS). Limit of detection (LOD) of 1E-4 ng/mL (i.e. 1 pg/mL) at 7% CV (coefficient of variation) for cTnT in HS was demonstrated on nanostructured ZnO electrodes. The mechanical integrity of the flexible biosensor platform was demonstrated with cyclic bending tests. The sensor performed within 12% CV after 100 bending cycles demonstrating the robustness of the nanostructured ZnO electrochemical sensor platform.

Electrochemically Exfoliated High‐Quality 2H‐MoS2 for Multiflake Thin Film Flexible Biosensors

“…Remarkably, the results obtained using this relatively cheap and simple fabrication method, are comparable or even outperform some of the recently reported flexible electrical devices based either on single MoS 2 flakes (2.2–10 mm) or chemical vapor deposition (CVD) grown (9–14 mm), and others fabricated in polyimide supports using various materials such as organic films (28 mm), silicon nanowires (7.5 mm), graphene (4 mm), or ZnO nanostructures (9 mm) …”

Achieving biosensing at attomolar concentrations of cardiac troponin T in human biofluids by developing a label-free nanoplasmonic analytical assay

“…Our chip-based LSPR cTnT biosensor provides a limit of detection (LOD) as low as 507 fg/L, which is 10 4 fold more sensitive than the commercial Elecys troponin T electrolumi-nescense immunoassay (ECLIA, 4 th generation, Roche Diagnostic) 18 and at least 50 fold lower than other label-free analytical techniques. 19,20 The initial LSPR biosensor work by the Chilkoti 21 and Van Duyne 13 groups demonstrated that in chip-based sensors, fabrication requires three important steps: (i) Immobilization of chemicallysynthesized/lithographically-fabricated nanoparticles onto suitable transparent solid substrates.…”

Metal oxide nanostructures for sensor applications

“…Several reports have demonstrated the application of ZnO as biosensors, i.e. in DNA immobilization [180], in glucose level detection [176,177,181], for cardiac biomarker detection [179,182,183] and also for cancer diagnostic [178,184,185].…”