Summary statement8 Box-Behnken model is an efficient method to optimized process conditions of 9 microencapsules strength for long-term cell culture, promotes CHO cells viability and 10 protein production in a stirred tank bioreactor.11 not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/165464 doi: bioRxiv preprint first posted online Jul. 19, 2017; 2 ABSTRACT: Cell microencapsulation technology has been proved to be a valuable 1 technology in the fields of large-scale cell culture. It is important to accurately construct the 2 microcapsule membranes with desired properties including a certain thickness suitable for cell 3 growth, and maximum strength for the stability of microencapsules. As single factor 4 experiments are time-consuming to obtain the desired membrane preparation conditions, 5 Box-Behnken model was used to investigate the interactions among reaction conditions, 6 predict the optimized reaction conditions for given purpose, that was membrane with 7 maximum strength and desired thickness for microencapsulated cell culture. Significant values 8 of R 2 in this study indicated the model theoretical values are very close to the measured values. 9 Based on the desired membrane thickness, the process of maximum strength was optimized, 10 and the prediction agreement of measured value and model theoretical value was 91.11%.
11The optimized microencapsules with maximum strength and 15 μm membrane thickness 12 promote CHO cells viability and protein production in stirred tank bioreactor. The result 13 shows that Box-Behnken model is an efficient method to optimized process conditions of 14 microencapsules strength for long-term cell culture. 15