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Published on: February 27, 2020
A Robust and Automated Platform for Charge Detection Mass Spectrometry of Megadalton Biotherapeutics
Samuel E Janisse1, Ryan T Fellers1,2, Shannon A Raab3
1Proteomics Center of Excellence, Northwestern University, Evanston, Illinois 60208, United States.
Abstract:
Gene therapies based on adeno-associated viruses are an emerging area with high potential to improve human health. Current quality control techniques to assess contaminates and byproducts from the adeno-associated virus (AAV) production pipelines are lacking in robustness and throughput. To address these limitations, we coupled an automated microfluidic device called SampleStream with Orbitrap-based charge detection mass spectrometry (SS-CDMS). We demonstrate that the SS-CDMS workflow performs AAV analysis in under 15 min per sample in a completely autonomous manner. The SS-CDMS workflow enables rapid assessment of key quality control attributes (CQAs), such as of molecular weight and content ratio of AAV formulations with a small sample requirement (<2 × 109 capsids) without being limited by sample concentration. Additionally, this work shows the potential for the SS-CDMS workflow to be implemented at various stages of the production pipeline through effective sample clean up from more complex AAV matrices such as cell culture media.
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