Development of an electrochemical biosensor with TiN nano-electrode arrays for IL-6 detection

In this study, we developed a novel electrochemical biosensor for detecting IL-6 that uses a nano-electrode array (NEA) fabricated via standard CMOS processing. Miniaturizing the electrodes to the nanoscale and arranging them in an array to form an NEA facilitated the creation of a higher electric field magnitude, compared to that available via the use of microelectrodes, that could be used to improve biosensor sensitivity. Additionally, the array configuration of the NEA aided in providing sufficient reaction sites. Each nano-electrode in the NEA was cylindrically shaped, with a radius of 0.1 µm, and a top layer formed by TiN physical vapor deposition, and each biosensor was divided into four independent banks, with each bank including a set of WE, CE and RE. These banks were capable of independently inputting and outputting electrical signals. This design allowed the NEA biosensor to undergo selective modification by CV input. In this study, we discuss and address material and contamination issues associated with CMOS-produced NEAs and their uses as biosensors. To ameliorate these issues, we stored materials and products in a nitrogen-controlled cabinet and conducted pretreatment cleaning on the electrodes. Both steps had a noticeable impact on the cleanliness of the electrode surfaces. These optimized conditions resulted in a remarkable 96.6% reduction in Rct. The NEA surface was functionalized by electrochemically grafting diazonium salts subsequently immobilized with anti-IL-6 antibodies via EDC/NHS chemistry. The resulting NEA biosensor demonstrated sufficient sensitivity to rapidly distinguish inflammatory conditions and disease severity. This showcases the potential for using NEA devices mass-produced via standard CMOS processing as electrodes for biosensors.