A microfluidic optical platform for real-time monitoring of pH and oxygen in microfluidic bioreactors and organ-on-chip devices

Abstract

There is a growing interest to develop microfluidic bioreactors and organ-on-chipplatforms with integrated sensors to monitor their physicochemical properties and tomaintain a well-controlled microenvironment for cultured organoids. Conventionalsensing devices cannot be easily integrated with microfluidic organ-on-chip systemswith low-volume bioreactors for continual monitoring. This paper reports on thedevelopment of a multi-analyte optical sensing module for dynamic measurementsof pH and dissolved oxygen levels in the culture medium. The sensing system wasconstructed using low-cost electro-optics including light-emitting diodes and siliconphotodiodes. The sensing module includes an optically transparent window formeasuring light intensity, and the module could be connected directly to a perfusionbioreactor without any specific modifications to the microfluidic device design. Acompact, user-friendly, and low-cost electronic interface was developed to controlthe optical transducer and signal acquisition from photodiodes. The platformenabled convenient integration of the optical sensing module with a microfluidicbioreactor. Human dermal fibroblasts were cultivated in the bioreactor, and thevalues of pH and dissolved oxygen levels in the flowing culture medium were measuredcontinuously for up to 3 days. Our integrated microfluidic system providesa new analytical platform with ease of fabrication and operation, which can beadapted for applications in various microfluidic cell culture and organ-on-chipdevices.