Integrated Bioluminescent Immunoassays for High-Throughput Sampling and Continuous Monitoring of Cytokines
Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleuk...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2023-06, Vol.95 (23), p.8922-8931 |
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| creator | van Aalen, Eva A. Rosier, Bas J. H. M. Jansen, Tom Wouters, Simone F. A. Vermathen, Robin T. van der Veer, Harmen J. Yeste Lozano, José Mughal, Sheeza Fernández-Costa, Juan M. Ramón-Azcón, Javier den Toonder, Jaap M. J. Merkx, Maarten |
| description | Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques. |
| doi_str_mv | 10.1021/acs.analchem.3c00745 |
| format | Article |
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H. M. ; Jansen, Tom ; Wouters, Simone F. A. ; Vermathen, Robin T. ; van der Veer, Harmen J. ; Yeste Lozano, José ; Mughal, Sheeza ; Fernández-Costa, Juan M. ; Ramón-Azcón, Javier ; den Toonder, Jaap M. J. ; Merkx, Maarten</creator><creatorcontrib>van Aalen, Eva A. ; Rosier, Bas J. H. M. ; Jansen, Tom ; Wouters, Simone F. A. ; Vermathen, Robin T. ; van der Veer, Harmen J. ; Yeste Lozano, José ; Mughal, Sheeza ; Fernández-Costa, Juan M. ; Ramón-Azcón, Javier ; den Toonder, Jaap M. J. ; Merkx, Maarten</creatorcontrib><description>Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.3c00745</identifier><identifier>PMID: 37253113</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Bioluminescence ; Biosensors ; Breast cancer ; Breast carcinoma ; Chemistry ; Cytokines ; Digital cameras ; Endotoxins ; High-throughput screening ; Immunoassay ; Immunoassays ; Interleukin 6 ; Interleukins ; Low concentrations ; Microfluidic devices ; Microfluidics ; Monitoring ; Protein G ; Three dimensional models ; Tumor necrosis factor-α</subject><ispartof>Analytical chemistry (Washington), 2023-06, Vol.95 (23), p.8922-8931</ispartof><rights>2023 The Authors. 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H. M.</creatorcontrib><creatorcontrib>Jansen, Tom</creatorcontrib><creatorcontrib>Wouters, Simone F. A.</creatorcontrib><creatorcontrib>Vermathen, Robin T.</creatorcontrib><creatorcontrib>van der Veer, Harmen J.</creatorcontrib><creatorcontrib>Yeste Lozano, José</creatorcontrib><creatorcontrib>Mughal, Sheeza</creatorcontrib><creatorcontrib>Fernández-Costa, Juan M.</creatorcontrib><creatorcontrib>Ramón-Azcón, Javier</creatorcontrib><creatorcontrib>den Toonder, Jaap M. J.</creatorcontrib><creatorcontrib>Merkx, Maarten</creatorcontrib><title>Integrated Bioluminescent Immunoassays for High-Throughput Sampling and Continuous Monitoring of Cytokines</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.</description><subject>Bioluminescence</subject><subject>Biosensors</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Chemistry</subject><subject>Cytokines</subject><subject>Digital cameras</subject><subject>Endotoxins</subject><subject>High-throughput screening</subject><subject>Immunoassay</subject><subject>Immunoassays</subject><subject>Interleukin 6</subject><subject>Interleukins</subject><subject>Low concentrations</subject><subject>Microfluidic devices</subject><subject>Microfluidics</subject><subject>Monitoring</subject><subject>Protein G</subject><subject>Three dimensional models</subject><subject>Tumor necrosis factor-α</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS0EokPhDRCyxIZNpv6NnRWiI6AjFXXRsracxE48JPZgO0jz9iTMdARdsPLifudcn3sAeIvRGiOCr3ST1trroenNuKYNQoLxZ2CFOUFFKSV5DlYIIVoQgdAFeJXSDiGMES5fggsqCKcY0xXYbX02XdTZtPDahWEanTepMT7D7ThOPuiU9CFBGyK8cV1fPPQxTF2_nzK81-N-cL6D2rdwE3x2fgpTgt-CdznEZRIs3Bxy-LGYvgYvrB6SeXN6L8H3L58fNjfF7d3X7ebTbaGZkLmQTd2WVcVwJanl1pqaylJW2mLaUEKorWjDeGmpxUxqSgyyQgrS1oTWlvGGXoKPR9_9VI-mXbJEPah9dKOOBxW0U_9OvOtVF36p-aylkLKaHT6cHGL4OZmU1ejmmwyD9mYOqIgkmDKGkZjR90_QXZjiXMsfikvBOV4M2ZFqYkgpGnv-DUbLWqzmNtVjm-rU5ix793eSs-ixvhlAR2CRnxf_1_M30KexWg</recordid><startdate>20230613</startdate><enddate>20230613</enddate><creator>van Aalen, Eva A.</creator><creator>Rosier, Bas J. 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H. M. ; Jansen, Tom ; Wouters, Simone F. A. ; Vermathen, Robin T. ; van der Veer, Harmen J. ; Yeste Lozano, José ; Mughal, Sheeza ; Fernández-Costa, Juan M. ; Ramón-Azcón, Javier ; den Toonder, Jaap M. 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H. M.</au><au>Jansen, Tom</au><au>Wouters, Simone F. A.</au><au>Vermathen, Robin T.</au><au>van der Veer, Harmen J.</au><au>Yeste Lozano, José</au><au>Mughal, Sheeza</au><au>Fernández-Costa, Juan M.</au><au>Ramón-Azcón, Javier</au><au>den Toonder, Jaap M. J.</au><au>Merkx, Maarten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrated Bioluminescent Immunoassays for High-Throughput Sampling and Continuous Monitoring of Cytokines</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2023-06-13</date><risdate>2023</risdate><volume>95</volume><issue>23</issue><spage>8922</spage><epage>8931</epage><pages>8922-8931</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>37253113</pmid><doi>10.1021/acs.analchem.3c00745</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-9484-3882</orcidid><orcidid>https://orcid.org/0000-0002-4359-8079</orcidid><orcidid>https://orcid.org/0000-0002-3636-8013</orcidid><orcidid>https://orcid.org/0000-0002-1854-6082</orcidid><orcidid>https://orcid.org/0000-0002-0062-7087</orcidid><orcidid>https://orcid.org/0000-0001-8006-8627</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Analytical chemistry (Washington), 2023-06, Vol.95 (23), p.8922-8931 |
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| source | ACS Publications |
| subjects | Bioluminescence Biosensors Breast cancer Breast carcinoma Chemistry Cytokines Digital cameras Endotoxins High-throughput screening Immunoassay Immunoassays Interleukin 6 Interleukins Low concentrations Microfluidic devices Microfluidics Monitoring Protein G Three dimensional models Tumor necrosis factor-α |
| title | Integrated Bioluminescent Immunoassays for High-Throughput Sampling and Continuous Monitoring of Cytokines |
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