Ultra-thin inorganic oxide and nitride films as an alternative blocking layer for electrochemical sensors

The desire to translate biosensors for real time molecular monitoring has intensified due to the commercial success of 2-week continuous glucose monitors. However, a common limitation for emerging biosensors is that their lifetimes are often too short for commercially expected benchmarks of at least 3-day and ideally 2-week operation. Electrochemical sensors remain the preferred format of biochemical sensing thanks to their low cost, size, weight, and power requirements for mobile deployment. When exposed to biological fluid, all electrochemical sensors require a blocking layer to protect the electrode surface from fouling and redox interferents. Traditional blocking layer approaches rely on self-assembled monolayers which are often fragile to biological interferents like proteins and require specific electrode materials to improve their stability. Presented here is an evaluation of ultra-thin inorganic oxide and nitride films as an alternative to self-assembled monolayer blocking layers. Specifically, silicon oxide, silicon nitride, and aluminum oxide films were deposited by electron beam evaporation or atomic layer deposition at thicknesses of several nanometers to mimic the electrical capacitance of a conventional monolayer blocking layer. These oxide films were characterized over 7-days and demonstrated to provide poor protection against interfering redox currents from dissolved ferricyanide (150 - 300 µA/cm2) and oxygen reduction interference (30 - 60 µA/cm2). The oxide films were then used as a blocking layer in an electrochemical aptamer sensor using the previously published aptamer for phenylalanine. The phenylalanine sensor showed a binding affinity stronger than found in literature, but a reduced signal gain (∼ 20 % change in methylene blue redox current compared to the expected 50 % previously published on gold). It is speculated and supported by literature that these oxide and nitride films gradually dissolve over periods of days in an aqueous environment. Results further show that if lower quality oxide or nitride films are used, they may be more stable, but at the cost of initially higher in currents. While oxide and nitride films fail to improve upon the performance of thiol-blocking layers on gold electrodes, they may provide utility in some applications by allowing for alternate electrode materials and surfaces to be used instead of traditional self-assembled monolayers on gold electrodes.