Miniaturized pH Holographic Sensors for the Monitoring of Lactobacillus casei Shirota Growth in a Microfluidic Chip

Bioreactors have been used both to develop new, and to improve bioprocess yields for, biopharmaceutical products. However, efforts to miniaturize bioreactors, in order to save costs and accelerate process development times, have been limited by the lack of on-site monitoring capabilities available at such scales. In this study, small volume (3 nL) nonconsumptive holographic sensors were integrated into a glass-PDMS microfluidic chip to monitor via a blue-shift in the resultant holographic replay wavelength, the change in pH during microbial growth of Lactobacillus casei (L. casei) Shirota. Within the optimal growth pH range of L. casei, the accuracy of the miniaturized pH sensors was comparable to that of a conventional pH meter. Conceivably, this approach could be extrapolated to an array of miniaturized holographic sensors sensitive to different analytes, and thereby paving the way for reliable, real-time, noninvasive monitoring of microorganisms in a nanobioreactor.