<p dir="ltr">Biopharmaceutical manufacturing efforts are gradually shifting toward single-use bioreactors (SUB) because of their lower cost and modular scalability. One challenge that hinders further adoption of SUBs is the lack of sensors that can be integrated into sterile equipment, while being cost-effective for disposal with the SUB at the end of its operational life.</p><p dir="ltr">In this dissertation I discuss the development of γ-irradiated thin-film sensors that provide accurate pH monitoring in sterile media, with a focus on the reference electrode (RE). Thin-film Ag/AgCl REs exhibit excellent stability across a pH range of 4.5–9.0 and are inert to various organic species, for up to 60 days post irradiation. Notably, γ-irradiation of a thin-film pH sensor (pH electrode plus RE) produces a logarithmic voltage decay that can be readily corrected by a single-point calibration function. These sensors can accurately report pH changes in sterile cell culture media over several weeks.</p><p dir="ltr">The scalable production of thin-film pH sensors can be achieved by optimizing a semi-automated fabrication process for membrane deposition. Improvements in process control are fortified by a comprehensive uncertainty analysis to determine the relative contributions of error from manufacturing, measurement, and data analysis. Identifying key sources of uncertainty enables further optimization of the fabrication process as well as sensor performance.</p><p dir="ltr">This dissertation also includes a discussion on novel approaches for reducing the conditioning time of thin-film REs, a current impediment for their rapid deployment. Studies include the effects of autoclaving on membrane permeability and tuning the porosity of prefabricated membranes, and their impacts on ion flux across a high-impedance barrier. Changes in permeability produces a trade-off between conditioning speed and potentiometric inertness of the RE, but also reveals insights for future efforts to improve electrode performance.</p>