On-Chip Nanostructuring of Gold Microelectrodes in Phosphate-Buffered Saline for Broadband Single-Cell Impedance Biosensors

Impedance-based single-cell sensors are gaining increased interest due to their affordability, potential for miniaturization and label-free nature. However, their sensitivity is restricted due to the electrical double layer effect which prevents accurate assessment of cell properties at low frequencies, e.g., cell size and membrane properties. This effect becomes increasingly problematic when the electrode size is reduced since then the double layer impedance dominates up to higher frequencies. This paper describes an extremely fast (1 s) technique for on-chip nanostructuring of gold microelectrodes that can be used for single cell impedance sensors. The developed technique achieves a 40-fold reduction in double layer impedance at 1 kHz by nanostructuring ready-made gold coplanar microelectrodes on chip without requiring extra fabrication steps. The technique uses only a DC voltage source and a 100× diluted phosphate-buffered saline (PBS) solution, making it cost-effective, nonhazardous, and ideally suited for a batch process. A comparison of single-cell impedance measurements of Saccharomyces cerevisiae yeast using bare and nanostructured microelectrodes shows improved reproducibility and accuracy for frequencies below 100 kHz.