Nandhinee Radha Shanmugam

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.

Biofouling and foreign body responses have deleterious effects on the functionality and longevity of implantable biosensors, seriously impeding their implementation for long-term monitoring. Here, we describe a nanocomposite coating composed of a cross-linked lattice of bovine serum albumin and pentaamine-functionalized reduced graphene that is covalently coupled to antibody ligands for analyte detection as well as antibiotic drugs (gentamicin or ceftriaxone), which actively combats biofouling while retaining high electroconductivity and excellent electrochemical immunosensor behavior. Sensors overlaid with this coating inhibit the proliferation of Pseudomonas aeruginosa bacteria and adhesion of primary human fibroblasts while not having any significant effects on fibroblast viability or on the immune function of primary human monocytes. Under these conditions, the sensor maintains its electrochemical stability for at least 3 weeks after exposure to soluble proteins that interfere with the activity of uncoated sensors. Proof-of-concept for the coating’s applicability is demonstrated by integrating the antimicrobial coating within an immunosensor and demonstrating the detection of cytokines in both culture medium and complex human plasma. This new coating technology holds the potential to substantially increase the lifespan of implanted biosensors and widen their application areas, potentially enabling continuous monitoring of analytes in complex biofluids for weeks in vivo.

Continuous glucose monitoring is valuable for people with diabetes but faces limitations due to enzyme–electrode interactions and biofouling from biological samples that reduce sensor sensitivity and the monitoring performance. We created an enzyme-based electrochemical system with a unique nanocomposite coating that incorporates the redox molecule, aminoferrocene (NH₂-Fc). This coating enhances stability via electroactivity and reduces nonspecific binding, as demonstrated through cyclic voltammetry. Our approach enables real-time glucose detection via chronoamperometry with a calculated linear range of 0.5 to 20 mM and a 1 mM detection limit. Validated with plasma and saliva, this platform shows promise for robust metabolite detection in clinical and research contexts. This versatile platform can be applied to accurately monitor a wide range of metabolites in various biological matrices, improving patient outcomes.

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 analytical performance of affinity immunoassay based biosensor systems is determined by the efficiency of capture probe immobilization, which in turn depends on the stability of surface modification. In this study, we investigate the functionalization of nanostructured ZnO surfaces through two types of crosslinker molecules – DSP that favors thiol chemistry and 11-AUPA that favors phosphonic acid bonding. The type of interaction and surface composition of functionalized ZnO surfaces were evaluated using Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) measurements. The crosslinker interaction with ZnO surfaces and subsequent biomolecular binding events influence the inherent electrical properties at the ZnO electrode–electrolyte interface. The changes in charge perturbations due to these events are leveraged for the sensing of target biomolecules, and cardiac troponin-I (cTnI) is investigated using Electrochemical Impedance Spectroscopy and Mott–Schottky measurements. Our results demonstrate that Zn–S formation is more sensitive for the detection of cTnI as compared to the ZnO–AUPA interactions. The dynamic range of detection is from 0.1 pg mL⁻¹ to 100 000 pg mL⁻¹ with a limit of detection at 0.1 pg mL⁻¹ in human serum.

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.