Current
biomanufacturing relies on long lead-time analytical tests for both in-process monitoring (IPM)
and final product release. These testing methods significantly increases the cost and the product-to-
market release time.
Current in-line or on-line analytical methods can't measure multiple variables across different categories simultaneously. Tracking various process parameters and product attributes requires integrating multiple sensing technologies, increasing system integration challenges and costs. There's an urgent need for adaptable, multi-attribute, cross-category in-line sensing technology for different biomanufacturing steps, regardless of scale or product.
This project develops a multi-attribute in-line
optochemical sensor platform for continuous monitoring of bioreactors at all scales. The
optochemical sensor employs low-cost hydrogel sensors and miniature optical fiber devices, for
in-situ monitoring of key process parameters and product quality attributes in both solution and
vapor phases. This multiplexed fiber-optic sensor platform will monitor, for the first time, crosscategory
variables, such as dissolved O2 (DO), dissolved CO2 (DCO), metabolites (e.g., glucose),
and volatile emissions from cell cultures. A prototype device will be demonstrated and validated
for continuous monitoring of Chinese hamster ovary (CHO) cell bioreactors within the project
period.
A hydrogel-based glucose sensor has been successfully prepared by using simple conjugation chemistry for continuous glucose sensing in the bioreactor.
A novel CO2sensor has also been developed by loading CO2-sensing dye, HPTS, into PDMS thin film for continuous and reversible CO2monitoring in the bioreactor.
A miniaturized fiber-optic reader has been prototyped for continuous reading of fluorescence signals from the glucose/CO2sensors in the bioreactor.
Multi-attribute in-line sensing of upstream process variables such as glucose, DO and DCO.
Reduce batch time from multiple weeks to several days.
Low cost optical fiber-coupled hydrogel sensor scalable to small and large scale bioreactors.
Hetzler, Z., Wang, Y., Krafft, D., Jamalzadegan, S., Overton, L., Kudenov, M. W., Ligler, F. S., & Wei, Q. (2022). Flexible sensor patch for continuous carbon dioxide monitoring. Frontiers in Chemistry, 10. https://doi.org/10.3389/fchem.2022.983523
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North Carolina State University
MilliporeSigma/EMD Serono
Pfizer, Inc.
