Very Accurate Flexible pH Microsensor Based on Nanoporous Titanium Nitride Material for In Vivo Application

Recently, the need for a real-time and less invasive solution to replace in-laboratory blood analysis by analyzing in situ biological fluids (sweat, saliva, tear, urine, and interstitial fluid) has grown alongside the development of microfabrication techniques. pH determination is crucial for health monitoring (e.g., fetal acidosis supervision, sport activity, tumor detection, and wound monitoring). Our work focuses on developing a potentiometric microsensor, targeting pH measurement on the fetal scalp during labor, employing nanoporous titanium nitride (TiN) as an alternative sensing material. The pH probe contains a working electrode (WE) of 400 x 800 mu m in size, integrated on a flexible polyimide (PI) substrate, creating an ultrathin sensor with thickness below 20 mu m. Microfabrication process and a complete characterization on performance of our flexible pH microsensor are presented, demonstrating a sensitivity of 53.2 mV/pH. Hysteresis was found at 3-mV maximum after six cycles, demonstrated a good reproducibility, and led to a precision of 0.05 in pH. A comparison of the performance between porous and flat TiN (sensitivity of 53.7 mV/pH, hysteresis maximum of 5 mV, and precision of 0.09 in pH) is presented, along with an evaluation of the dependence in the electrode size versus their performances. A preliminary in vivo test was conducted on mice with the probe implanted under the skin. We recorded a stable open-circuit voltage (OCV) signal under anesthesia conditions. A compact measurement system was designed with a customized liquid crystal display (LCD) screen for signal visualization, an EZO ORP circuit for data acquisition, and an integrated secure digital (SD card) for data storage.