Real time monitoring of bioreactor mAb IgG3 cell culture process dynamics via Fourier transform infrared spectroscopy： Implications for enabling cell culture process analytical technology

Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufac- turing biotechnology drug products. However, the use of inline Fourier transform infrared （FTIR） spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites （including glucose, glutamine, lactate, and ammonia） and protein yield at increasing levels of complexity （simple binary system, fully formulated media, actual bioreactor cell culture process） was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares （PLS） calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2＇ld derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy. Its implications for enabling cell culture PAT were discussed.

Contrastive Rhetoric and Inter-language Theory

A learner’s stages of L2 development are connected by his or her L1 and culture.It is,accordingly,of paramount importance to understand the second language learners’culture and learning process and better assist them through this process in the way of teaching them English.Similarly,inter-language theory(IL)and contrastive rhetoric are affected by factors,such as learner’s L1,learning experiences,and culture.This paper talks about these two theory’s characteristics,constructs,and importance,so language instructors may better understand the L2 learning phenomena and think out better methods to help language learners improve their language skills.

Some Knacks of Studying English Writing： From My Own Learning Experience

A learner's stages of L2 development are connected by his or her L1 and culture. It is, accordingly, of paramount impor-tance to understand the second language learners' culture and learning process and better assist them through this process in theway of teaching them English writing.This essay has demonstrated several elements which affect learners' English writing throughmy own experiences, such as different cultures, reading and correct recognition of writing, and the writing process.