Recent advances in metal oxide, bimetallic nanocomposites, metal-organic frameworks (MOFs), and non-invasive technologies for biofluid-based glucose sensors: A comprehensive review

Abstract

The field of glucose biosensors for diabetes control has experienced enormous scientific and technological developments since it was first introduced in the 1960s, with electrochemical biosensors emerging as the most promising platform for real-time, dynamic glucose monitoring due to the high precision, versatility and compatibility with wearable devices. Over the past decade, wearable healthcare technologies have significantly advanced, enabling non-invasive or minimally invasive monitoring of biomarkers in peripheral biofluids such as sweat, saliva, tears and interstitial fluid (ISF) through electrochemical sensing. While enzymatic biosensors, particularly those employing glucose oxidase (GOx), remain prevalent for their sensitivity, challenges such as enzyme instability and limited shelf life persist. In response, non-enzymatic have gained prominence, leveraging nanostructure materials like metal oxides (e.g., NiO, CuO, ZnO), metal-organic frameworks (MOFs) and bimetallic composites (e.g., CuCo-MOFs) to achieve superior sensitivity, stability and catalytic performance. These materials exploit high surface-to-volume ratios, tuneable porosity and synergistic effects to overcome limitations such as pH sensitivity and poor conductivity. Innovations in material design, including laser-induced (LIG) and hybrid composites (eg., MXene/rGO), further enhance electron transfer and these materials enable low detection limits, wide linear ranges and rapid response time. This review comprehensively examines recent enzyme-free glucose sensors, focusing on the advancement of nanomaterials and their integration into wearable platforms such as microneedle-based ISF monitor contact lens sensors for tear analysis and hydrogel patches for sweat glucose detection. We critically evaluate the current state of biofluid sensing, addressing challenges in accuracy mad scalability while highlighting the convergence of advanced nanomaterials.