Bioreactors are used at large scale to manufacture vital protein therapeutics such as monoclonal antibodies (mAbs) and at small scale for personalized live-cell therapies such as anti-cancer CAR-T. Minor variations in manufacturing materials or conditions can cause substantial changes to safety, efficacy, and yield of the final biotherapeutic, and these changes can happen in minutes or hours. Therefore, the ability to chemically characterize an ongoing bioreaction is a critical measurement need, and relating this information to the therapeutic's quality attributes is a vital research area. Since the state of the cellular growth medium reflects the state of the bioreaction, nuclear magnetic resonance (NMR)-based metabolomics measurements of growth media can be used to non-destructively quantify the metabolites consumed and secreted during the bioreaction, thus providing an ideal approach to characterize a bioreaction in real time.

We will explore the use of low-field, benchtop NMR as an in-line detector to monitor and characterize a bioreaction. NMR can monitor several hundred metabolites in a single measurement. We will utilize this capability to characterize the metabolic flux - in real time - in the cellular growth media and work towards designing a sterile closed-loop system that can safely exclude cells while directing bioreactor media through an in-line flow NMR sample cell. We will evaluate biotherapeutic production modalities from mAb production by CHO cells to clinically prepared reference cell lines derived from healthy donors to emulate CAR-T cell therapy. We aim to develop computational methods for analyzing the spectral data produced, ultimately creating dynamic models that facilitate adaptive control of the biomanufacturing reaction.

key words

Biomanufacturing; monoclonal antibodies; nuclear magnetic resonance; NMR; spectral analysis; machine learning; metabolomics; biotherapeutics; in-line measurement; CHO cells

Citizenship:  Open to U.S. citizens

Level:  Open to Postdoctoral applicants