Development of a High-Throughput Mass Spectrometry-Based SARS-CoV-2 Immunoassay
The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2024-01, Vol.96 (1), p.12-17 |
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| creator | Sun, Jie Song, Jong Hee Danielson, Mary K. Colley, Nathan D. Thomas, Alia Hambly, David Barnes, Jonathan C. Gross, Michael L. |
| description | The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. This strategy is also applicable for the detection of other disease antigens besides SARS-CoV-2. |
| doi_str_mv | 10.1021/acs.analchem.3c02421 |
| format | Article |
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Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. 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Chem</addtitle><description>The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. This strategy is also applicable for the detection of other disease antigens besides SARS-CoV-2.</description><subject>Antibodies</subject><subject>Antigens</subject><subject>Conjugates</subject><subject>COVID-19</subject><subject>COVID-19 - diagnosis</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Immunoassay - methods</subject><subject>Ionization</subject><subject>Lasers</subject><subject>Mass spectrometry</subject><subject>Mass Spectrometry - methods</subject><subject>Mass spectroscopy</subject><subject>Pandemics</subject><subject>Reproducibility of Results</subject><subject>SARS-CoV-2</subject><subject>Scientific imaging</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike protein</subject><subject>Viral diseases</subject><issn>0003-2700</issn><issn>1520-6882</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS0EotvCN0AoEhcuXsb_EueEykJppaJKbOFqeZ3JJlUSBzuptN8er3a7Ag6c5uDfe_PGj5A3DJYMOPtgXVzawXauwX4pHHDJ2TOyYIoDzbXmz8kCAATlBcAZOY_xAYAxYPlLciY0g7IoYUHuPuMjdn7scZgyX2c2u263Db1vgp-3zThP2TcbY7Ye0U3B9ziFHf1kI1bZ-vL7mq78T8qzm76fB584u3tFXtS2i_j6OC_Ij6sv96trenv39WZ1eUutFHyicuNKrSpMmQVsuMLCCawEK6HmquaaV1prpiTawnKGUmmhpQSZO5ErLQtxQT4efMd502PlUvxgOzOGtrdhZ7xtzd8vQ9uYrX806XAoldbJ4f3RIfhfM8bJ9G102HV2QD9Hw0sQWpV5kSf03T_og59D-vs9xYQCBqASJQ-UCz7GgPUpDQOzr8ykysxTZeZYWZK9_fOSk-ipowTAAdjLT4v_6_kbJzmj_g</recordid><startdate>20240109</startdate><enddate>20240109</enddate><creator>Sun, Jie</creator><creator>Song, Jong Hee</creator><creator>Danielson, Mary K.</creator><creator>Colley, Nathan D.</creator><creator>Thomas, Alia</creator><creator>Hambly, David</creator><creator>Barnes, Jonathan C.</creator><creator>Gross, Michael L.</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1159-4636</orcidid><orcidid>https://orcid.org/0000-0002-9683-7213</orcidid><orcidid>https://orcid.org/0000-0003-2945-8691</orcidid></search><sort><creationdate>20240109</creationdate><title>Development of a High-Throughput Mass Spectrometry-Based SARS-CoV-2 Immunoassay</title><author>Sun, Jie ; Song, Jong Hee ; Danielson, Mary K. ; Colley, Nathan D. ; Thomas, Alia ; Hambly, David ; Barnes, Jonathan C. ; Gross, Michael L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a432t-4bc985de42130b25e7c3ed3190f25f282d888154ea7a21e4583844046c3658473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antibodies</topic><topic>Antigens</topic><topic>Conjugates</topic><topic>COVID-19</topic><topic>COVID-19 - diagnosis</topic><topic>Humans</topic><topic>Immunoassay</topic><topic>Immunoassay - methods</topic><topic>Ionization</topic><topic>Lasers</topic><topic>Mass spectrometry</topic><topic>Mass Spectrometry - methods</topic><topic>Mass spectroscopy</topic><topic>Pandemics</topic><topic>Reproducibility of Results</topic><topic>SARS-CoV-2</topic><topic>Scientific imaging</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Spike protein</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Jie</creatorcontrib><creatorcontrib>Song, Jong Hee</creatorcontrib><creatorcontrib>Danielson, Mary K.</creatorcontrib><creatorcontrib>Colley, Nathan D.</creatorcontrib><creatorcontrib>Thomas, Alia</creatorcontrib><creatorcontrib>Hambly, David</creatorcontrib><creatorcontrib>Barnes, Jonathan C.</creatorcontrib><creatorcontrib>Gross, Michael L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Jie</au><au>Song, Jong Hee</au><au>Danielson, Mary K.</au><au>Colley, Nathan D.</au><au>Thomas, Alia</au><au>Hambly, David</au><au>Barnes, Jonathan C.</au><au>Gross, Michael L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a High-Throughput Mass Spectrometry-Based SARS-CoV-2 Immunoassay</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2024-01-09</date><risdate>2024</risdate><volume>96</volume><issue>1</issue><spage>12</spage><epage>17</epage><pages>12-17</pages><issn>0003-2700</issn><issn>1520-6882</issn><eissn>1520-6882</eissn><abstract>The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. This strategy is also applicable for the detection of other disease antigens besides SARS-CoV-2.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>38109790</pmid><doi>10.1021/acs.analchem.3c02421</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-1159-4636</orcidid><orcidid>https://orcid.org/0000-0002-9683-7213</orcidid><orcidid>https://orcid.org/0000-0003-2945-8691</orcidid></addata></record> |
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| subjects | Antibodies Antigens Conjugates COVID-19 COVID-19 - diagnosis Humans Immunoassay Immunoassay - methods Ionization Lasers Mass spectrometry Mass Spectrometry - methods Mass spectroscopy Pandemics Reproducibility of Results SARS-CoV-2 Scientific imaging Severe acute respiratory syndrome coronavirus 2 Spike protein Viral diseases |
| title | Development of a High-Throughput Mass Spectrometry-Based SARS-CoV-2 Immunoassay |
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