Scalable Manufacturing of Radiation-Tolerant Potentiometric Electrodes: A Systematic Transition from Laboratory to Semiautomated Fabrication

Abstract

A “lab-to-fab” transition is described that enables the semiautomated production of thin-film potentiometric pH electrodes, designed for use in sterile single-use bioreactors. Manual methods of materials deposition and film casting are replaced with spray coating on a moving web and the production of membranes with a programmable dispenser operating at constant rates. These provide a greater degree of control over membrane thickness and a reduction in voltage spread between electrodes, which are evaluated in batches using a multichannel analyzer. γ-ray ionization of the pH electrodes introduces a predictable voltage drift that follows a log decay function on the day timescale; the voltage decay rate correlates with membrane thickness and can be modeled as a parallel diode–capacitor circuit. Batches of radiation-sterilized pH electrodes are tested in cell culture media and yield mean pH values within 0.05 units relative to a commercial meter (ground truth) following a single-point calibration protocol. Quantitative uncertainty analysis attributes more than half of total error to variations caused by ionizing radiation and yields novel insights into strategies for reducing uncertainty.