Nandhinee Radha Shanmugam, Joshua Rainbow, Jeong‐Chan Lee, Pawan Jolly, Donald E. Ingber
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.