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A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections

Applying MALDI-ToF mass spectrometry as a clinical diagnostic test for viruses is different from that of bacteria, fungi and other micro-organisms. This is because the systems biology of viral infections, the size and chemical nature of specific viral proteins and the mass spectrometry biophysics of...

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Autores principales: Iles, Ray K., Iles, Jason K., Zmuidinaite, Raminta, Roberts, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501081/
https://www.ncbi.nlm.nih.gov/pubmed/36146765
http://dx.doi.org/10.3390/v14091958
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author Iles, Ray K.
Iles, Jason K.
Zmuidinaite, Raminta
Roberts, Michael
author_facet Iles, Ray K.
Iles, Jason K.
Zmuidinaite, Raminta
Roberts, Michael
author_sort Iles, Ray K.
collection PubMed
description Applying MALDI-ToF mass spectrometry as a clinical diagnostic test for viruses is different from that of bacteria, fungi and other micro-organisms. This is because the systems biology of viral infections, the size and chemical nature of specific viral proteins and the mass spectrometry biophysics of how they are quantitated are fundamentally different. The analytical challenges to overcome when developing a clinical MALDI-ToF mass spectrometry tests for a virus, particularly human pathogenic enveloped viruses, are sample enrichment, virus envelope disruption, optimal matrix formulation, optimal MALDI ToF MS performance and optimal spectral data processing/bioinformatics. Primarily, the instrument operating settings have to be optimized to match the nature of the viral specific proteins, which are not compatible with setting established when testing for bacterial and many other micro-organisms. The capacity to be a viral infection clinical diagnostic instrument often stretches current mass spectrometers to their operational design limits. Finally, all the associated procedures, from sample collection to data analytics, for the technique have to meet the legal and operational requirement for often high-throughput clinical testing. Given the newness of the technology, clinical MALDI ToF mass spectrometry does not fit in with standard criteria applied by regulatory authorities whereby numeric outputs are compared directly to similar technology tests that have already been authorized for use. Thus, CLIA laboratory developed test (LDT) criteria have to be applied. This article details our experience of developing a SAR-CoV-2 MALDI-ToF MS test suitable for asymptomatic carrier infection population screening.
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spelling pubmed-95010812022-09-24 A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections Iles, Ray K. Iles, Jason K. Zmuidinaite, Raminta Roberts, Michael Viruses Review Applying MALDI-ToF mass spectrometry as a clinical diagnostic test for viruses is different from that of bacteria, fungi and other micro-organisms. This is because the systems biology of viral infections, the size and chemical nature of specific viral proteins and the mass spectrometry biophysics of how they are quantitated are fundamentally different. The analytical challenges to overcome when developing a clinical MALDI-ToF mass spectrometry tests for a virus, particularly human pathogenic enveloped viruses, are sample enrichment, virus envelope disruption, optimal matrix formulation, optimal MALDI ToF MS performance and optimal spectral data processing/bioinformatics. Primarily, the instrument operating settings have to be optimized to match the nature of the viral specific proteins, which are not compatible with setting established when testing for bacterial and many other micro-organisms. The capacity to be a viral infection clinical diagnostic instrument often stretches current mass spectrometers to their operational design limits. Finally, all the associated procedures, from sample collection to data analytics, for the technique have to meet the legal and operational requirement for often high-throughput clinical testing. Given the newness of the technology, clinical MALDI ToF mass spectrometry does not fit in with standard criteria applied by regulatory authorities whereby numeric outputs are compared directly to similar technology tests that have already been authorized for use. Thus, CLIA laboratory developed test (LDT) criteria have to be applied. This article details our experience of developing a SAR-CoV-2 MALDI-ToF MS test suitable for asymptomatic carrier infection population screening. MDPI 2022-09-03 /pmc/articles/PMC9501081/ /pubmed/36146765 http://dx.doi.org/10.3390/v14091958 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Iles, Ray K.
Iles, Jason K.
Zmuidinaite, Raminta
Roberts, Michael
A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections
title A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections
title_full A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections
title_fullStr A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections
title_full_unstemmed A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections
title_short A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections
title_sort how to guide: clinical population test development and authorization of maldi-tof mass spectrometry-based screening tests for viral infections
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501081/
https://www.ncbi.nlm.nih.gov/pubmed/36146765
http://dx.doi.org/10.3390/v14091958
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