Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood

Abstract Bloodstream infections (BSI) caused by pathogenic bacteria are a global health threat, highlighting the need for improved diagnostic methods. Current methods, such as mass spectrometry, depend on time-consuming blood cultures, which hinder timely diagnosis. Nucleic acid amplification tests...

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Main Authors: Dong Jin M. Park, Tianqi Wu, Liben Chen, Pei-Wei Lee, Kuangwen Hsieh, Tza-Huei Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-08987-z
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author Dong Jin M. Park
Tianqi Wu
Liben Chen
Pei-Wei Lee
Kuangwen Hsieh
Tza-Huei Wang
author_facet Dong Jin M. Park
Tianqi Wu
Liben Chen
Pei-Wei Lee
Kuangwen Hsieh
Tza-Huei Wang
author_sort Dong Jin M. Park
collection DOAJ
description Abstract Bloodstream infections (BSI) caused by pathogenic bacteria are a global health threat, highlighting the need for improved diagnostic methods. Current methods, such as mass spectrometry, depend on time-consuming blood cultures, which hinder timely diagnosis. Nucleic acid amplification tests (NAATs) offer potential for sensitive bacteria detection but are bottlenecked by the inability to isolate bacteria at low concentrations from blood. This study introduces a facile dual filter workflow for isolating low concentrations of bacteria from blood without blood culture. The workflow, which involves blood dilution and osmolysis, blood cell filtration, chemical and enzymatic lysis, and filter-based bacteria capture, can be completed in ~ 30 min without special equipment. It readily combines with downstream broad-based bacteria detection via PCR and high-resolution melt (HRM), as well as pheno-molecular antimicrobial susceptibility testing (AST) via PCR. When coupled with species-specific PCR, ~ 10 CFU of bacteria in 0.5 mL of blood could be detected. The small sample volume is particularly attractive because it is comparable to those obtained from fingerstick collections or pediatric patients. With further optimization, testing with a wider range of bacteria, and integration with rapid point-of-care testing, this simple dual filter workflow can be a key driver for advancing blood culture-free bacterial BSI diagnosis, especially in resource-limited settings.
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spelling doaj-art-e540fad6403941f185904a8bb1d24b8f2025-08-20T04:01:52ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-08987-zSimple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from bloodDong Jin M. Park0Tianqi Wu1Liben Chen2Pei-Wei Lee3Kuangwen Hsieh4Tza-Huei Wang5Department of Biomedical Engineering, Johns Hopkins UniversityDepartment of Biomedical Engineering, Johns Hopkins UniversityDepartment of Mechanical Engineering, Johns Hopkins UniversityDepartment of Mechanical Engineering, Johns Hopkins UniversityDepartment of Mechanical Engineering, Johns Hopkins UniversityDepartment of Biomedical Engineering, Johns Hopkins UniversityAbstract Bloodstream infections (BSI) caused by pathogenic bacteria are a global health threat, highlighting the need for improved diagnostic methods. Current methods, such as mass spectrometry, depend on time-consuming blood cultures, which hinder timely diagnosis. Nucleic acid amplification tests (NAATs) offer potential for sensitive bacteria detection but are bottlenecked by the inability to isolate bacteria at low concentrations from blood. This study introduces a facile dual filter workflow for isolating low concentrations of bacteria from blood without blood culture. The workflow, which involves blood dilution and osmolysis, blood cell filtration, chemical and enzymatic lysis, and filter-based bacteria capture, can be completed in ~ 30 min without special equipment. It readily combines with downstream broad-based bacteria detection via PCR and high-resolution melt (HRM), as well as pheno-molecular antimicrobial susceptibility testing (AST) via PCR. When coupled with species-specific PCR, ~ 10 CFU of bacteria in 0.5 mL of blood could be detected. The small sample volume is particularly attractive because it is comparable to those obtained from fingerstick collections or pediatric patients. With further optimization, testing with a wider range of bacteria, and integration with rapid point-of-care testing, this simple dual filter workflow can be a key driver for advancing blood culture-free bacterial BSI diagnosis, especially in resource-limited settings.https://doi.org/10.1038/s41598-025-08987-zBloodstream infectionsBlood processingBlood culture-freeSensitivityRapid diagnosisResource-limited settings
spellingShingle Dong Jin M. Park
Tianqi Wu
Liben Chen
Pei-Wei Lee
Kuangwen Hsieh
Tza-Huei Wang
Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood
Scientific Reports
Bloodstream infections
Blood processing
Blood culture-free
Sensitivity
Rapid diagnosis
Resource-limited settings
title Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood
title_full Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood
title_fullStr Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood
title_full_unstemmed Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood
title_short Simple dual filter workflow for facilitating blood culture-free and sensitive detection of pathogenic bacteria from blood
title_sort simple dual filter workflow for facilitating blood culture free and sensitive detection of pathogenic bacteria from blood
topic Bloodstream infections
Blood processing
Blood culture-free
Sensitivity
Rapid diagnosis
Resource-limited settings
url https://doi.org/10.1038/s41598-025-08987-z
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