Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting

Sample preparation (i.e., isolation and purification of pathogens from samples) remains one of the bottlenecks limiting deployment of diagnostic tests. Two recent examples highlighting these limitations include the difficulties in widespread nucleic acid testing during COVID-19 and in identifying dr...

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Main Authors: Jessica Martinez, Dong Jin M. Park, Samantha Abate, James Hill, George Downey, Craig Galligan, Tyler Hammond, Michael T. McCurdy, Surekha Gurung, Shanjana Shawon, Ralf Lenigk, Kuangwen Hsieh, Michael Super, Erik Kvam, Tza-Huei Wang, Coleman Murray, Chris Puleo
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:SLAS Technology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2472630325000731
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author Jessica Martinez
Dong Jin M. Park
Samantha Abate
James Hill
George Downey
Craig Galligan
Tyler Hammond
Michael T. McCurdy
Surekha Gurung
Shanjana Shawon
Ralf Lenigk
Kuangwen Hsieh
Michael Super
Erik Kvam
Tza-Huei Wang
Coleman Murray
Chris Puleo
author_facet Jessica Martinez
Dong Jin M. Park
Samantha Abate
James Hill
George Downey
Craig Galligan
Tyler Hammond
Michael T. McCurdy
Surekha Gurung
Shanjana Shawon
Ralf Lenigk
Kuangwen Hsieh
Michael Super
Erik Kvam
Tza-Huei Wang
Coleman Murray
Chris Puleo
author_sort Jessica Martinez
collection DOAJ
description Sample preparation (i.e., isolation and purification of pathogens from samples) remains one of the bottlenecks limiting deployment of diagnostic tests. Two recent examples highlighting these limitations include the difficulties in widespread nucleic acid testing during COVID-19 and in identifying drug-resistant infections. Unmet needs include systems that work with different bodily fluids and samples, multiple types of suspected pathogen, and function in a rapid and semi-automated fashion. Advances such as these could accelerate the deployment of novel diagnostic tests by eliminating upstream sample preparation bottlenecks.Herein, we tested the feasibility of combining multiple pathogen-binding paramagnetic beads with magnetic ratcheting-based enrichment to directly isolate microbes from samples. We demonstrate effective use of three different paramagnetic bead-conjugated proteins (mannose binding lection [MBL], C-reactive protein [CRP], and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN]) to capture 18 different bacteria species and model virus particles/peptides. We used magnetic ratcheting to isolate bead-bound microbes from milliliters (mLs) of sample at concentrations of 4 – 4000 microbes per mL. The flow-through system was operated up to 1 mL per minute and enabled pathogen isolation from 10 mL samples in <30 min. Demonstration of post-ratcheting PCR-based microbe analysis was also performed, showing that the technology may have applicability across different infectious agents, sample types/volumes, and analytical assays. Based on these results, further studies are warranted to test clinical samples, compare results to current gold-standard diagnostic methods, and test the sample preparation technologies across additional pathogen types.
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spelling doaj-art-03a1f18836474f409bf4c5fd5916d9452025-08-20T04:00:27ZengElsevierSLAS Technology2472-63032025-08-013310031510.1016/j.slast.2025.100315Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratchetingJessica Martinez0Dong Jin M. Park1Samantha Abate2James Hill3George Downey4Craig Galligan5Tyler Hammond6Michael T. McCurdy7Surekha Gurung8Shanjana Shawon9Ralf Lenigk10Kuangwen Hsieh11Michael Super12Erik Kvam13Tza-Huei Wang14Coleman Murray15Chris Puleo16General Electric Healthcare Technology and Innovation Center, 1 Research Circle, Niskayuna, NY 12309, USAJohns Hopkins University, Baltimore, MD 21218, USAGeneral Electric Healthcare Technology and Innovation Center, 1 Research Circle, Niskayuna, NY 12309, USABOA Biomedical, 20 University Rd., Cambridge, MA 02138, USABOA Biomedical, 20 University Rd., Cambridge, MA 02138, USAGeneral Electric Healthcare Technology and Innovation Center, 1 Research Circle, Niskayuna, NY 12309, USAGeneral Electric Healthcare Technology and Innovation Center, 1 Research Circle, Niskayuna, NY 12309, USABOA Biomedical, 20 University Rd., Cambridge, MA 02138, USA; University of Maryland School of Medicine, Baltimore, MD 21201, USARensselaer Polytechnic Institute, Troy, NY 12180, USARensselaer Polytechnic Institute, Troy, NY 12180, USAGeneral Electric Healthcare Technology and Innovation Center, 1 Research Circle, Niskayuna, NY 12309, USAJohns Hopkins University, Baltimore, MD 21218, USAWyss Institute, Harvard University, 201 Brookline Ave, Boston, MA 02215, USAGeneral Electric Healthcare Technology and Innovation Center, 1 Research Circle, Niskayuna, NY 12309, USAJohns Hopkins University, Baltimore, MD 21218, USAFerrologix, 23328 Barfield Dr, Valencia, CA 91354, USARensselaer Polytechnic Institute, Troy, NY 12180, USA; Corresponding author.Sample preparation (i.e., isolation and purification of pathogens from samples) remains one of the bottlenecks limiting deployment of diagnostic tests. Two recent examples highlighting these limitations include the difficulties in widespread nucleic acid testing during COVID-19 and in identifying drug-resistant infections. Unmet needs include systems that work with different bodily fluids and samples, multiple types of suspected pathogen, and function in a rapid and semi-automated fashion. Advances such as these could accelerate the deployment of novel diagnostic tests by eliminating upstream sample preparation bottlenecks.Herein, we tested the feasibility of combining multiple pathogen-binding paramagnetic beads with magnetic ratcheting-based enrichment to directly isolate microbes from samples. We demonstrate effective use of three different paramagnetic bead-conjugated proteins (mannose binding lection [MBL], C-reactive protein [CRP], and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN]) to capture 18 different bacteria species and model virus particles/peptides. We used magnetic ratcheting to isolate bead-bound microbes from milliliters (mLs) of sample at concentrations of 4 – 4000 microbes per mL. The flow-through system was operated up to 1 mL per minute and enabled pathogen isolation from 10 mL samples in <30 min. Demonstration of post-ratcheting PCR-based microbe analysis was also performed, showing that the technology may have applicability across different infectious agents, sample types/volumes, and analytical assays. Based on these results, further studies are warranted to test clinical samples, compare results to current gold-standard diagnostic methods, and test the sample preparation technologies across additional pathogen types.http://www.sciencedirect.com/science/article/pii/S2472630325000731Magnetic ratchetingDiagnosticsPathogenInfectious diseaseSample preparationAutomation
spellingShingle Jessica Martinez
Dong Jin M. Park
Samantha Abate
James Hill
George Downey
Craig Galligan
Tyler Hammond
Michael T. McCurdy
Surekha Gurung
Shanjana Shawon
Ralf Lenigk
Kuangwen Hsieh
Michael Super
Erik Kvam
Tza-Huei Wang
Coleman Murray
Chris Puleo
Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
SLAS Technology
Magnetic ratcheting
Diagnostics
Pathogen
Infectious disease
Sample preparation
Automation
title Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
title_full Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
title_fullStr Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
title_full_unstemmed Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
title_short Sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
title_sort sample preparation using multiple microbial pattern recognition proteins and magnetic bead ratcheting
topic Magnetic ratcheting
Diagnostics
Pathogen
Infectious disease
Sample preparation
Automation
url http://www.sciencedirect.com/science/article/pii/S2472630325000731
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