Patterned thin film enzyme electrodes via spincoating and glutaraldehyde vapor crosslinking: towards scalable fabrication of integrated sensor-on-CMOS devices

Effective continuous glucose monitoring solutions require consistent sensor performance over the lifetime of the device, a manageable variance between devices, and the capability of high volume, low cost production. Here we present a novel and microfabrication-compatible method of depositing and stabilizing enzyme layers on top of planar electrodes that can aid in the mass production of sensors while also improving their consistency. This work is focused on the fragile biorecognition layer as that has been a critical difficulty in the development of microfabricated sensors. We test this approach with glucose oxidase (GOx) and evaluate the sensor performance with amperometric measurements of in vitro glucose concentrations. Spincoating was used to deposit a uniform enzyme layer across a wafer, which was subsequently immobilized via glutaraldehyde vapor crosslinking and patterned via liftoff. This yielded an approximately 300 nm thick sensing layer which was applied to arrays of microfabricated platinum electrodes built on blank wafers. Taking advantage of their planar array format, measurements were then performed in high-throughput parallel instrumentation. Due to their thin structure, the coated electrodes exhibited subsecond stabilization times after the bias potential was applied. The deposited enzyme layers were measured to provide a sensitivity of 2.3 ± 0.2 μA mM⁻¹ mm⁻² with suitable saturation behavior and minimal performance shift observed over extended use. The same methodology was then demonstrated directly on top of wireless CMOS potentiostats to build a monolithic sensor with similar measured performance. This work demonstrates the effectiveness of the combination of spincoating and vapor stabilization processes for wafer scale enzymatic sensor functionalization and the potential for scalable fabrication of monolithic sensor-on-CMOS devices.