{"doi":"10.1021/acs.analchem.4c06397","title":"A Robust and Automated Platform for Charge Detection Mass Spectrometry of Megadalton Biotherapeutics","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 × 10 9 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.","journal":"Analytical Chemistry","year":2025,"id":517929,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247289,"name":"Ryan T. Fellers","orcid":"0000-0002-0710-3462","position":1,"is_corresponding":false},{"id":324712,"name":"Shannon A. Raab","orcid":null,"position":2,"is_corresponding":false},{"id":1385366,"name":"Michael P. Goodwin","orcid":null,"position":3,"is_corresponding":false},{"id":1094459,"name":"K. P. Bowen","orcid":"0000-0003-2483-8863","position":4,"is_corresponding":false},{"id":1384883,"name":"Zhirui Lian","orcid":"0000-0002-6873-1251","position":5,"is_corresponding":false},{"id":247288,"name":"Kenneth R. Durbin","orcid":"0000-0001-7163-4877","position":6,"is_corresponding":false},{"id":247293,"name":"Michael W. Senko","orcid":"0009-0000-5040-5776","position":7,"is_corresponding":false},{"id":247294,"name":"Philip D. Compton","orcid":"0000-0001-5212-7175","position":8,"is_corresponding":false},{"id":247286,"name":"Jared O. Kafader","orcid":"0000-0002-5359-264X","position":9,"is_corresponding":false},{"id":237416,"name":"Neil L. Kelleher","orcid":"0000-0002-8815-3372","position":10,"is_corresponding":false},{"id":958530,"name":"Samuel E. Janisse","orcid":"0000-0001-6625-8846","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T02:49:04.756302Z","pmid":"39967556","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}