A rapid and label-free platform for virus capture and identification from clinical samples

Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with...

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Vydané v:	Proceedings of the National Academy of Sciences - PNAS Ročník 117; číslo 2; s. 895
Hlavní autori:	Yeh, Yin-Ting, Gulino, Kristen, Zhang, YuHe, Sabestien, Aswathy, Chou, Tsui-Wen, Zhou, Bin, Lin, Zhong, Albert, Istvan, Lu, Huaguang, Swaminathan, Venkataraman, Ghedin, Elodie, Terrones, Mauricio
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 14.01.2020
Predmet:	Humans Influenza A virus - isolation & purification Microbiological Techniques - instrumentation Microbiological Techniques - methods Microtechnology - methods Nanotubes, Carbon Respiratory Tract Infections - diagnosis Respiratory Tract Infections - virology Respirovirus - isolation & purification Rhinovirus - isolation & purification Sensitivity and Specificity Silicon Dioxide Spectrum Analysis, Raman - methods Staining and Labeling Virion Virology - instrumentation Virology - methods Virus Diseases - diagnosis Virus Diseases - virology Viruses - genetics Viruses - isolation & purification virus isolation microfabrication carbon nanotube infectious disease sequencing
ISSN:	1091-6490, 1091-6490
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Abstract	Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with differential filtration porosity for the rapid enrichment and optical identification of viruses. Different emerging strains (or unknown viruses) can be enriched and identified in real time through a multivirus capture component in conjunction with surface-enhanced Raman spectroscopy. More importantly, after viral capture and detection on a chip, viruses remain viable and get purified in a microdevice that permits subsequent in-depth characterizations by various conventional methods. We validated this platform using different subtypes of avian influenza A viruses and human samples with respiratory infections. This technology successfully enriched rhinovirus, influenza virus, and parainfluenza viruses, and maintained the stoichiometric viral proportions when the samples contained more than one type of virus, thus emulating coinfection. Viral capture and detection took only a few minutes with a 70-fold enrichment enhancement; detection could be achieved with as little as 10 EID /mL (50% egg infective dose per microliter), with a virus specificity of 90%. After enrichment using the device, we demonstrated by sequencing that the abundance of viral-specific reads significantly increased from 4.1 to 31.8% for parainfluenza and from 0.08 to 0.44% for influenza virus. This enrichment method coupled to Raman virus identification constitutes an innovative system that could be used to quickly track and monitor viral outbreaks in real time.
AbstractList	Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with differential filtration porosity for the rapid enrichment and optical identification of viruses. Different emerging strains (or unknown viruses) can be enriched and identified in real time through a multivirus capture component in conjunction with surface-enhanced Raman spectroscopy. More importantly, after viral capture and detection on a chip, viruses remain viable and get purified in a microdevice that permits subsequent in-depth characterizations by various conventional methods. We validated this platform using different subtypes of avian influenza A viruses and human samples with respiratory infections. This technology successfully enriched rhinovirus, influenza virus, and parainfluenza viruses, and maintained the stoichiometric viral proportions when the samples contained more than one type of virus, thus emulating coinfection. Viral capture and detection took only a few minutes with a 70-fold enrichment enhancement; detection could be achieved with as little as 102 EID50/mL (50% egg infective dose per microliter), with a virus specificity of 90%. After enrichment using the device, we demonstrated by sequencing that the abundance of viral-specific reads significantly increased from 4.1 to 31.8% for parainfluenza and from 0.08 to 0.44% for influenza virus. This enrichment method coupled to Raman virus identification constitutes an innovative system that could be used to quickly track and monitor viral outbreaks in real time.Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with differential filtration porosity for the rapid enrichment and optical identification of viruses. Different emerging strains (or unknown viruses) can be enriched and identified in real time through a multivirus capture component in conjunction with surface-enhanced Raman spectroscopy. More importantly, after viral capture and detection on a chip, viruses remain viable and get purified in a microdevice that permits subsequent in-depth characterizations by various conventional methods. We validated this platform using different subtypes of avian influenza A viruses and human samples with respiratory infections. This technology successfully enriched rhinovirus, influenza virus, and parainfluenza viruses, and maintained the stoichiometric viral proportions when the samples contained more than one type of virus, thus emulating coinfection. Viral capture and detection took only a few minutes with a 70-fold enrichment enhancement; detection could be achieved with as little as 102 EID50/mL (50% egg infective dose per microliter), with a virus specificity of 90%. After enrichment using the device, we demonstrated by sequencing that the abundance of viral-specific reads significantly increased from 4.1 to 31.8% for parainfluenza and from 0.08 to 0.44% for influenza virus. This enrichment method coupled to Raman virus identification constitutes an innovative system that could be used to quickly track and monitor viral outbreaks in real time. Emerging and reemerging viruses are responsible for a number of recent epidemic outbreaks. A crucial step in predicting and controlling outbreaks is the timely and accurate characterization of emerging virus strains. We present a portable microfluidic platform containing carbon nanotube arrays with differential filtration porosity for the rapid enrichment and optical identification of viruses. Different emerging strains (or unknown viruses) can be enriched and identified in real time through a multivirus capture component in conjunction with surface-enhanced Raman spectroscopy. More importantly, after viral capture and detection on a chip, viruses remain viable and get purified in a microdevice that permits subsequent in-depth characterizations by various conventional methods. We validated this platform using different subtypes of avian influenza A viruses and human samples with respiratory infections. This technology successfully enriched rhinovirus, influenza virus, and parainfluenza viruses, and maintained the stoichiometric viral proportions when the samples contained more than one type of virus, thus emulating coinfection. Viral capture and detection took only a few minutes with a 70-fold enrichment enhancement; detection could be achieved with as little as 10 EID /mL (50% egg infective dose per microliter), with a virus specificity of 90%. After enrichment using the device, we demonstrated by sequencing that the abundance of viral-specific reads significantly increased from 4.1 to 31.8% for parainfluenza and from 0.08 to 0.44% for influenza virus. This enrichment method coupled to Raman virus identification constitutes an innovative system that could be used to quickly track and monitor viral outbreaks in real time.
Author	Zhou, Bin Ghedin, Elodie Lu, Huaguang Gulino, Kristen Chou, Tsui-Wen Swaminathan, Venkataraman Lin, Zhong Sabestien, Aswathy Zhang, YuHe Yeh, Yin-Ting Terrones, Mauricio Albert, Istvan
Author_xml	– sequence: 1 givenname: Yin-Ting orcidid: 0000-0002-1512-9267 surname: Yeh fullname: Yeh, Yin-Ting email: yxy155@psu.edu, mut11@psu.edu organization: Department of Physics, The Pennsylvania State University, University Park, PA 16802; yxy155@psu.edu mut11@psu.edu – sequence: 2 givenname: Kristen surname: Gulino fullname: Gulino, Kristen organization: Department of Biology, New York University, New York, NY 10003 – sequence: 3 givenname: YuHe surname: Zhang fullname: Zhang, YuHe organization: Department of Physics, The Pennsylvania State University, University Park, PA 16802 – sequence: 4 givenname: Aswathy surname: Sabestien fullname: Sabestien, Aswathy organization: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802 – sequence: 5 givenname: Tsui-Wen surname: Chou fullname: Chou, Tsui-Wen organization: Department of Biology, New York University, New York, NY 10003 – sequence: 6 givenname: Bin surname: Zhou fullname: Zhou, Bin organization: Department of Biology, New York University, New York, NY 10003 – sequence: 7 givenname: Zhong surname: Lin fullname: Lin, Zhong organization: Department of Physics, The Pennsylvania State University, University Park, PA 16802 – sequence: 8 givenname: Istvan surname: Albert fullname: Albert, Istvan organization: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802 – sequence: 9 givenname: Huaguang surname: Lu fullname: Lu, Huaguang organization: Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802 – sequence: 10 givenname: Venkataraman surname: Swaminathan fullname: Swaminathan, Venkataraman organization: Department of Physics, The Pennsylvania State University, University Park, PA 16802 – sequence: 11 givenname: Elodie orcidid: 0000-0002-1515-725X surname: Ghedin fullname: Ghedin, Elodie organization: Department of Biology, New York University, New York, NY 10003 – sequence: 12 givenname: Mauricio orcidid: 0000-0003-0010-2851 surname: Terrones fullname: Terrones, Mauricio email: yxy155@psu.edu, mut11@psu.edu organization: Department of Physics, The Pennsylvania State University, University Park, PA 16802; yxy155@psu.edu mut11@psu.edu
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/31882450$$D View this record in MEDLINE/PubMed
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SubjectTerms	Humans Influenza A virus - isolation & purification Microbiological Techniques - instrumentation Microbiological Techniques - methods Microtechnology - methods Nanotubes, Carbon Respiratory Tract Infections - diagnosis Respiratory Tract Infections - virology Respirovirus - isolation & purification Rhinovirus - isolation & purification Sensitivity and Specificity Silicon Dioxide Spectrum Analysis, Raman - methods Staining and Labeling Virion Virology - instrumentation Virology - methods Virus Diseases - diagnosis Virus Diseases - virology Viruses - genetics Viruses - isolation & purification
Title	A rapid and label-free platform for virus capture and identification from clinical samples
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