Measurement quality metrics to improve absolute microbial cell counting

Total and viable microbial cell counts are increasingly important for applications including live biotherapeutic products, food safety, and probiotics. In microbiology, cells are quantified using methods such as colony forming unit (CFU), flow cytometry, and polymerase chain reaction (PCR), but diff...

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Main Authors: Kirsten Parratt, David Newton, Joy Dunkers, Jennifer Dootz, Monique Hunter, Alshae' Logan-Jackson, Laura Pierce, Sumona Sarkar, Stephanie L. Servetas, Nancy J. Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1631377/full
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author Kirsten Parratt
David Newton
Joy Dunkers
Jennifer Dootz
Monique Hunter
Alshae' Logan-Jackson
Laura Pierce
Sumona Sarkar
Stephanie L. Servetas
Nancy J. Lin
author_facet Kirsten Parratt
David Newton
Joy Dunkers
Jennifer Dootz
Monique Hunter
Alshae' Logan-Jackson
Laura Pierce
Sumona Sarkar
Stephanie L. Servetas
Nancy J. Lin
author_sort Kirsten Parratt
collection DOAJ
description Total and viable microbial cell counts are increasingly important for applications including live biotherapeutic products, food safety, and probiotics. In microbiology, cells are quantified using methods such as colony forming unit (CFU), flow cytometry, and polymerase chain reaction (PCR), but different methods measure different aspects of the cells (measurands), and results may not be directly comparable across methods. In the absence of a ground-truth reference material for cell count, one cannot quantify the accuracy of any cell counting method, which limits method performance assessments and comparisons. Herein, a modified analysis of cell counting methods based on the ISO 20391-2:2019 standard was developed and demonstrated for microbial cell samples diluted over a log-scale range of concentrations. Escherichia coli samples ranging in concentration from ~5 x 105 cells/mL to 2 x 107 cells/mL were quantified using CFU, Coulter principle, fluorescence flow cytometry, and impedance flow cytometry. Quality metrics modified from the ISO standard were calculated for each method and shown to be repeatable across replicate experiments. The quality metrics illustrate large differences in proportionality and variability across methods, with total cell counts in good agreement and viable cell count having more variability. As the ISO standard is meant to guide fit-for-purpose method selection, interpretation of the results and quality metrics can drive method choice and optimization. The framework introduced here will help researchers select fit-for-purpose counting methods for quantification of microbial total and viable cells across a range of applications.
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spelling doaj-art-244d976e71e2463a93c71b7a28452e272025-08-20T03:43:55ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-08-011610.3389/fmicb.2025.16313771631377Measurement quality metrics to improve absolute microbial cell countingKirsten Parratt0David Newton1Joy Dunkers2Jennifer Dootz3Monique Hunter4Alshae' Logan-Jackson5Laura Pierce6Sumona Sarkar7Stephanie L. Servetas8Nancy J. Lin9Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesStatistical Engineering Division, National Institute of Standards and Technology, Boulder, CO, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesBiosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United StatesTotal and viable microbial cell counts are increasingly important for applications including live biotherapeutic products, food safety, and probiotics. In microbiology, cells are quantified using methods such as colony forming unit (CFU), flow cytometry, and polymerase chain reaction (PCR), but different methods measure different aspects of the cells (measurands), and results may not be directly comparable across methods. In the absence of a ground-truth reference material for cell count, one cannot quantify the accuracy of any cell counting method, which limits method performance assessments and comparisons. Herein, a modified analysis of cell counting methods based on the ISO 20391-2:2019 standard was developed and demonstrated for microbial cell samples diluted over a log-scale range of concentrations. Escherichia coli samples ranging in concentration from ~5 x 105 cells/mL to 2 x 107 cells/mL were quantified using CFU, Coulter principle, fluorescence flow cytometry, and impedance flow cytometry. Quality metrics modified from the ISO standard were calculated for each method and shown to be repeatable across replicate experiments. The quality metrics illustrate large differences in proportionality and variability across methods, with total cell counts in good agreement and viable cell count having more variability. As the ISO standard is meant to guide fit-for-purpose method selection, interpretation of the results and quality metrics can drive method choice and optimization. The framework introduced here will help researchers select fit-for-purpose counting methods for quantification of microbial total and viable cells across a range of applications.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1631377/fullmeasurement quality metricsabsolute cell countmicrobial cell viabilityfluorescence flow cytometryimpedance flow cytometryCFU
spellingShingle Kirsten Parratt
David Newton
Joy Dunkers
Jennifer Dootz
Monique Hunter
Alshae' Logan-Jackson
Laura Pierce
Sumona Sarkar
Stephanie L. Servetas
Nancy J. Lin
Measurement quality metrics to improve absolute microbial cell counting
Frontiers in Microbiology
measurement quality metrics
absolute cell count
microbial cell viability
fluorescence flow cytometry
impedance flow cytometry
CFU
title Measurement quality metrics to improve absolute microbial cell counting
title_full Measurement quality metrics to improve absolute microbial cell counting
title_fullStr Measurement quality metrics to improve absolute microbial cell counting
title_full_unstemmed Measurement quality metrics to improve absolute microbial cell counting
title_short Measurement quality metrics to improve absolute microbial cell counting
title_sort measurement quality metrics to improve absolute microbial cell counting
topic measurement quality metrics
absolute cell count
microbial cell viability
fluorescence flow cytometry
impedance flow cytometry
CFU
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1631377/full
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