Single Nanowire Sensors for Intracellular Electrochemical Measurement

Cells serve as the fundamental unit underlying the structure and function of living organisms, demonstrating rapid responses and dynamic changes among various biochemical components within the cytoplasm and organelles. Any abnormal alterations in these components can lead to diseases. Thus, single-cell analysis is crucial for exploring life activities and understanding the causes of disease emergence and progression. Nanoelectrochemical sensors exhibit remarkable characteristics such as high spatiotemporal resolution, robust quantitative capabilities, and the ability to enable real-time monitoring of dynamic activities in specific cellular regions. The rapid advancement of nanotechnology along with the increasing demand for biological detection has created a need for more stringent technical standards for nanoelectrochemical sensors intended for single-cell analysis. First, significant breakthroughs are required in precision manufacturing processes for nanoscale tips to ensure that the sensors demonstrate ultralow invasiveness when penetrating cells. Additionally, the preparation processes for electrode materials must be optimized to facilitate scalable production while ensuring high stability and reproducibility. Furthermore, there is an urgent need to develop precise and controllable surface modification techniques that will yield highly specific and sensitive functionalized detection interfaces. The development of electrochemical nanosensors that satisfy these criteria will greatly enhance the ability to conduct highly sensitive and selective quantitative analyses of low-concentration components within individual cells.This Account presents a comprehensive overview of the development of advanced core-shell nanowire sensors specifically designed for single-cell-level detection. It encompasses flexible construction strategies and intracellular detection methods as well as their application in addressing significant physiological challenges. Typically, the nanowire sensor is made of nanowires with a core-shell structure. The core is a rigid nanowire with various diameters as the electrode skeleton, whereas the shell is a conductive and functionalized material as a sensing interface. Notably, conductive nanoshell layers with high catalytic properties can be synthesized in bulk and well-controlled on nanowire substrates. These flexible synthesis strategies allow the range of single nanowires to be extended beyond the limitations of the current electrode materials. Using nanofabrication techniques, these functional nanowires can be assembled into individual nanowire electrodes for highly sensitive monitoring of a single species or into multichannel nanowire sensors to analyze multiple targets simultaneously. Nanowire sensors are used to quantitatively monitor key species in cellular life processes by combining various detection modes (e.g., amperometry, potentiometry, and coulometry). Therefore, information about the concentration and kinetics of metabolite substances (e.g., NADH and ATP), redox species (e.g., ROS/RNS and GSH), and neurotransmitters (e.g., dopamine and glutamate) could be accurately obtained at the single and subcellular level. A deeper understanding of the mechanisms driving regular physiological changes and the pathogenesis within individual cells has emerged. In particular, significant discoveries have been made regarding the regulatory mechanisms of pharmacodynamics of anticancer drugs, redox homeostasis in macrophages, and the partial release patterns of neurotransmitters.