title: Implementing the Bruker MALDI Biotyper in the Public Health Laboratory for C. botulinum Neurotoxin Detection.
abstract: Currently, the gold standard method for active botulinum neurotoxin (BoNT) detection is the mouse bioassay (MBA). A Centers for Disease Control and Prevention-developed mass spectrometry (MS)-based assay that detects active BoNT was successfully validated and implemented in a public health laboratory in clinical matrices using the Bruker MALDI-TOF MS (Matrix-assisted laser desorption ionization-time of flight mass spectrometry) Biotyper. For the first time, a direct comparison with the MBA was performed to determine MS-based assay sensitivity using the Bruker MALDI Biotyper. Mice were injected with BoNT/A, /B, /E, and /F at concentrations surrounding the established MS assay limit of detection (LOD) and analyzed simultaneously. For BoNT/B, /E, and /F, MS assay sensitivity was equivalent or better than the MBA at 25, 0.3, and 8.8 mLD50, respectively. BoNT/A was detected by the MBA between 1.8 and 18 mLD50, somewhat more sensitive than the MS method of 18 mLD50. Studies were performed to compare assay performance in clinical specimens. For all tested specimens, the MS method rapidly detected BoNT activity and serotype in agreement with, or in the absence of, results from the MBA. We demonstrate that the MS assay can generate reliable, rapid results while eliminating the need for animal testing.
authors.affiliation: Biodefense Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA. michael.perry@health.ny.gov.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Perry
authors.affiliation: Biodefense Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA. dominick.centurioni@health.ny.gov.
authors.forename: Dominick A
authors.initials: DA
authors.lastname: Centurioni
authors.affiliation: Biodefense Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA. stephen.davis@health.ny.gov.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Davis
authors.affiliation: Bacteriology Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA. george.hannett@health.ny.gov.
authors.forename: George E
authors.initials: GE
authors.lastname: Hannett
authors.affiliation: Bacteriology Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA. kimberlee.musser@health.ny.gov.
authors.forename: Kimberlee A
authors.initials: KA
authors.lastname: Musser
authors.affiliation: Biodefense Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA. christina.egan@health.ny.gov.
authors.forename: Christina T
authors.initials: CT
authors.lastname: Egan
mesh_terms: D000818:Animals; D001681:Biological Assay; D001905:Botulinum Toxins / Q000032:analysis* / Q000097:blood; D005243:Feces / Q000737:chemistry; D006801:Humans; D007753:Laboratories; D057230:Limit of Detection; D051379:Mice; D009498:Neurotoxins / Q000032:analysis* / Q000097:blood; D011634:Public Health; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009498:Neurotoxins; D001905:Botulinum Toxins
keywords: Clostridium botulinum; mass spectrometry; mouse bioassay; toxin