Over the past few decades zinc oxide (ZnO)-based thin films and nanostructures have shown unprecedented performance in a wide range of applications. In particular, owing to high isoelectric point, biocompatibility and other multifunctional characteristics, ZnO has extensively been studied as a transduction material for biosensor development. The fascinating properties of ZnO help retain biological activity of the immobilized biomolecule and help in achieving enhanced sensing performance. As a consequence of recent advancements in this multidisciplinary field, diagnostic biosensors are expanding beyond traditional clinical labs to point-of-care and home settings. Label-free electrical detection of biomarkers has been demonstrated using ZnO-sensing platforms. In this review we highlight the characteristics of ZnO that enable realization of its use in development of point-of-care biosensors toward disease diagnosis, in particular cardiovascular diseases. Lay abstract The goal of this review is to discuss the features of ZnO in enhancing the sensitivity and selectivity of biomarker detection toward the development of point-of-care diagnostic devices. Basic biosensor design features and fabrication of ZnO nanostructures, strategies for surface modifications and its application toward disease diagnosis are discussed.

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.

Aim: Vertically oriented zinc oxide nanostructures based disposable diagnostic biosensor for detecting and quantifying levels of cardiac troponin-T from human serum has been developed. Materials & methods: The biosensors were designed by integrating hydrothermally grown zinc oxide nanostructures on glass and printed circuit board platforms, resulting in the generation of high-density nanostructure arrays with nanotextured zinc oxide based electrodes. The size, density and surface terminations of the nanostructures were leveraged toward achieving surface confinement of the target cTnT molecules on to the nanostructures. A combination of AC and DC spectroscopy was used to characterize the biosensor response to cTnT. Results & conclusion: LOD of 0.1 pg/ml in human serum was achieved.

Aim: Development of a label-free multiplexed point-of-care diagnostic device for a panel of cardiac biomarkers – cardiac troponin-T (cTnT), troponin-I (cTnI) and B-type natriuretic peptide (BNP). Methods: A nonfaradaic electrochemical immunoassay designed with anisotropic high surface area ZnO nanostructures grown using low-temperature hydrothermal methods was selectively immobilized with capture antibodies. Multiplexed detection in human serum using ZnO nanostructures based on complementary electrochemical measurement techniques – electrochemical impedance spectroscopy and Mott–Schottky. Results: Linear signal response for detection of three biomarkers in human serum with dynamic range of 1 pg/ml–100 ng/ml and limit of detection at 1 pg/ml and low signal response to background interferences was achieved. Conclusion: First demonstration of simultaneous detection of three cardiac biomarkers in clinically relevant range with sensor's analytical performance and linear response of detection showed potential u...

The evolution of label‐free electrochemical biosensors has revolutionized the field of analytical detection by enabling rapid, direct, and sensitive detection of a wide range of analytes. Electrochemical impedance spectroscopy (EIS) provides mechanistic insight into the interfacial changes occurring at the electrode/electrolyte interface, thereby enabling real‐time monitoring. Direct detection of molecular binding events at the electrode interface is made possible by sensing measurable shifts in interfacial impedance characteristics. Despite their versatility, the commercial translation of EIS‐enabled biosensors has been hindered by challenges in achieving robust sensitivity, specificity, and reproducibility. Recent progress in the field, including integration of nanoengineered electrode materials and novel biorecognition elements, has addressed some of these limitations, resulting in marked improvements in EIS‐based biosensor performance. This review discusses the mechanistic principles underlying label‐free EIS biosensing and highlights recent developments in electrode surface modification and sensor architecture. It also explores the integration of novel biorecognition elements and describes how their impact on sensor performance may be assessed. Current limitations and future directions for the application of EIS‐enabled sensors in clinical diagnostics, environmental analysis, and food safety monitoring are also considered.