title: Characterization and optimization of miniature implantable electrochemical oxygen sensors
Creators: name: Zhang, Shan
Publisher: name: The University of Edinburgh
Year: 2025
Subjects: subject: monitoring oxygen
subject: anastomotic leakage
subject: colorectal surgery
subject: Clark-type electrode
subject: micro-scale electrochemical oxygen sensor
subject: biofouling effect
subject: anti-biofouling membrane
subject: Nafion film

description: Colorectal surgery is a curative method for patients diagnosed with colorectal cancer. It involves the removal of cancerous intestinal tissue and the formation of an anastomosis – a surgical join reconnecting the two disease-free ends of the intestine. However, dangerous complications can occur at anastomoses after surgery, including anastomotic leakage (AL). This failure involves luminal contents leaking into the abdomen. Patients with AL have significantly increased morbidity and mortality, and it results in substantial additional healthcare costs. Therefore, technologies for timely AL detection to allow early-stage intervention are helpful in improving clinical outcomes. Tissue oxygenation is one of the critical parameters for detecting AL. Many technologies, such as visible light spectroscopy, pulse oximetry and near-infrared spectroscopy, have been applied for intra-operative sensing to reduce AL risk. However, these technologies are unable to actively monitor AL, which generally occurs 5 to 8 days after surgery. Thus, a real-time, continuous, and in-situ method is necessary for post-operational monitoring. In this project, a miniature implantable electrochemical oxygen sensor was developed to address this need. This sensor consists of a platinum microelectrode array, which serves as a working electrode (WE). At the surface of the WE, oxygen is reduced, and the reducing current is linearly related to the oxygen partial pressure (pO2). The WE was fabricated on a silicon substrate using conventional semiconductor technology. Wafer-level fabrication ensured excellent reproducibility and manufacturability. Compared to sensors with a single microelectrode, the microelectrode array increased the measured current and improved sensitivity to oxygen. An off-chip silver/silver chloride double-junction electrode was used as a combined counter electrode (CE) and reference electrode (RE). The use of an external RE extended the lifetime of the sensor. To mitigate the effects of biofouling after implantation, a thick (~ 600 μm) poly (2-hydroxyethyl methacrylate) hydrogel was drop-cast on the sensor. The performance of the membrane-coated sensor was characterized by performing chronoamperometry in vitro. The linearity and sensitivity of the device to oxygen concentration were tested. However, to improve shelf-life, a solid-state oxygen sensor was desired. Thus, the drop-cast sensor was dehydrated for storage and rehydrated in an electrolyte solution before use. There was minimal difference in electrochemical performance between the freshly produced sensor and the rehydrated sensor. This result suggested that the dehydration process did not affect the properties of the sensor and is a feasible strategy to produce the solid-state sensor. Additionally, a numerical model was developed to study the diffusion pattern in the oxygen sensor, and the simulated results were validated by experiments. Based on the verified model, the functionality of the thick membrane in mitigating biofouling was evaluated. The ability of the model to inform the optimal usage of the oxygen sensor, which is necessary for clinical use, was also demonstrated. Consistency between simulated and experimental results indicated that the numerical model could be utilized to produce new designs of oxygen sensors with various inter-electrode spacings or electrode radii. The model will minimise cost and time for future development by reducing the need for physical prototypes. A stable and reliable on-chip RE is a key component of a fully integrated oxygen sensor. One candidate is a chemically chlorinated Ag/AgCl electrode. However, the chlorination process is difficult to monitor on a thin-film silver. Thus, a more controllable and reproducible process was needed. A series of test structures were designed and developed to determine the percentage of the remaining silver. Variation in the sheet resistance of the test structures was measured as the concentration of reactants, reaction time, and geometry were varied. Cross-die and cross-wafer maps were generated to visualize the spatial distribution of sheet resistances. It indicates that the method is available to monitor the chlorination process at a wafer level. Finally, a Nafion membrane was explored as an alternative for producing a solid-state oxygen sensor. Creating a strong bond between the surface of the oxygen sensor and a thick Nafion film is vital to the performance of the devices. The factors involved in the bonding process, including the presence of an interlayer, annealing after drop coating interlayer, bonding temperature and pressure, were assessed. The optimal combination of the factors supporting the best adhesion was determined using 90-degree peel tests. The maximum force required to separate the Nafion film and the substrate was used to assess the adhesion strength quantitatively. The largest peel resistance was conducted by the components bonded at 120 °C without applying pressure and interlayer. This combination of bonding parameters would be used to produce the Nafion-coated oxygen sensors in the future.