{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T15:23:59Z","timestamp":1794410639782,"version":"4.9.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T00:00:00Z","timestamp":1520294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,3,6]],"date-time":"2018-03-06T00:00:00Z","timestamp":1520294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Direct detection of genetic biomarkers in body fluid lysate without target amplification will revolutionize nucleic acid-based diagnostics. However, the low concentration of target sequences makes this goal challenging. We report a method for direct detection of pathogen RNA in blood lysate using a bioassay using surface-enhanced Raman spectroscopy (SERS)-based detection integrated in a \u201clab-in-a-stick\u201d portable device. Two levels of signal enhancement were employed to achieve the sensitivity required for direct detection. Each target sequence was tagged with an ultrabright SERS-encoded nanorattle with ultrahigh SERS signals, and these tagged target sequences were concentrated into a focused spot for detection using hybridization sandwiches with magnetic microbeads. Furthermore, the washing process was automated by integration into a \u201clab-in-a-stick\u201d portable device. We could directly detect synthetic target with a limit of detection of 200\u2009fM. More importantly, we detected <jats:italic>plasmodium falciparum<\/jats:italic> malaria parasite RNA directly in infected red blood cells lysate. To our knowledge, this is the first report of SERS-based direct detection of pathogen nucleic acid in blood lysate without nucleic acid extraction or target amplification. The results show the potential of our integrated bioassay for field use and point-of-care diagnostics.<\/jats:p>","DOI":"10.1038\/s41598-018-21615-3","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T11:43:27Z","timestamp":1519818207000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Direct Detection of Unamplified Pathogen RNA in Blood Lysate using an Integrated Lab-in-a-Stick Device and Ultrabright SERS Nanorattles"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8609-1123","authenticated-orcid":false,"given":"Hoan T.","family":"Ngo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren Abelard","family":"Odion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Strobbia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agampodi Swarnapali","family":"De Silva Indrasekara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Vohra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve M.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3701-3326","authenticated-orcid":false,"given":"Tuan","family":"Vo-Dinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,6]]},"reference":[{"key":"21615_CR1","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.tibtech.2011.01.007","volume":"29","author":"A Niemz","year":"2011","unstructured":"Niemz, A., Ferguson, T. M. & Boyle, D. S. Point-of-care nucleic acid testing for infectious diseases. Trends in Biotechnology 29, 240\u2013250 (2011).","journal-title":"Trends in Biotechnology"},{"key":"21615_CR2","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1021\/jacs.6b10850","volume":"139","author":"SJ Smith","year":"2017","unstructured":"Smith, S. J., Nemr, C. R. & Kelley, S. O. Chemistry-Driven Approaches for Ultrasensitive Nucleic Acid Detection. J. Am. Chem. Soc. 139, 1020\u20131028 (2017).","journal-title":"J. Am. Chem. Soc."},{"key":"21615_CR3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.bios.2015.04.069","volume":"74","author":"X Zhu","year":"2015","unstructured":"Zhu, X. et al. Application of nanomaterials in the bioanalytical detection of disease-related genes. Biosens. Bioelectron. 74, 113\u2013133 (2015).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR4","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3390\/chemosensors3030224","volume":"3","author":"L Miotke","year":"2015","unstructured":"Miotke, L., Barducci, M. C. & Astakhova, K. Novel Signal-Enhancing Approaches for Optical Detection of Nucleic Acids-Going beyond Target Amplification. Chemosensors 3, 224\u2013240 (2015).","journal-title":"Chemosensors"},{"key":"21615_CR5","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1373\/clinchem.2005.065078","volume":"52","author":"Z Zheng","year":"2006","unstructured":"Zheng, Z., Luo, Y. L. & McMaster, G. K. Sensitive and quantitative measurement of gene expression directly from a small amount of whole blood. Clinical Chemistry 52, 1294\u20131302 (2006).","journal-title":"Clinical Chemistry"},{"key":"21615_CR6","first-page":"S59","volume":"28","author":"R D\u2019Agata","year":"2011","unstructured":"D\u2019Agata, R. et al. Detection of genomic disorders in unamplified human genomic DNA using an ultrasensitive surface plasmon resonance imaging method. Int J Mol Med 28, S59\u2013S59 (2011).","journal-title":"Int J Mol Med"},{"key":"21615_CR7","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.bios.2014.07.047","volume":"63","author":"A Bertucci","year":"2015","unstructured":"Bertucci, A. et al. Detection of unamplified genomic DNA by a PNA-based microstructured optical fiber (MOF) Bragg-grating optofluidic system. Biosens. Bioelectron. 63, 248\u2013254 (2015).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/srep14494","volume":"5","author":"H Cai","year":"2015","unstructured":"Cai, H. et al. Optofluidic analysis system for amplification-free, direct detection of Ebola infection. Sci Rep 5, 14494 (2015).","journal-title":"Sci Rep"},{"key":"21615_CR9","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.bios.2015.07.071","volume":"74","author":"S Mariani","year":"2015","unstructured":"Mariani, S., Scarano, S., Spadavecchia, J. & Minunni, M. A reusable optical biosensor for the ultrasensitive and selective detection of unamplified human genomic DNA with gold nanostars. Biosens. Bioelectron. 74, 981\u2013988 (2015).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bios.2015.11.013","volume":"78","author":"R Mayr","year":"2016","unstructured":"Mayr, R. et al. A microfluidic platform for transcription- and amplification-free detection of zepto-mole amounts of nucleic acid molecules. Biosens Bioelectron 78, 1\u20136 (2016).","journal-title":"Biosens Bioelectron"},{"key":"21615_CR11","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.bios.2015.12.057","volume":"79","author":"Y Xu","year":"2016","unstructured":"Xu, Y. & Zheng, Z. Direct RNA detection without nucleic acid purification and PCR: Combining sandwich hybridization with signal amplification based on branched hybridization chain reaction. Biosens. Bioelectron. 79, 593\u2013599 (2016).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR12","doi-asserted-by":"publisher","first-page":"4756","DOI":"10.1002\/anie.201205748","volume":"53","author":"S Schl\u00fccker","year":"2014","unstructured":"Schl\u00fccker, S. Surface-Enhanced Raman Spectroscopy: Concepts and Chemical Applications. Angew. Chem. Int. Edit. 53, 4756\u20134795 (2014).","journal-title":"Angew. Chem. Int. Edit."},{"key":"21615_CR13","doi-asserted-by":"publisher","first-page":"10489","DOI":"10.1021\/acs.chemrev.5b00265","volume":"115","author":"LA Lane","year":"2015","unstructured":"Lane, L. A., Qian, X. M. & Nie, S. M. SERS Nanoparticles in Medicine: From Label-Free Detection to Spectroscopic Tagging. Chem. Rev. 115, 10489\u201310529 (2015).","journal-title":"Chem. Rev."},{"key":"21615_CR14","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1103\/PhysRevLett.78.1667","volume":"78","author":"K Kneipp","year":"1997","unstructured":"Kneipp, K. et al. Single molecule detection using surface-enhanced Raman scattering (SERS). Phys. Rev. Lett. 78, 1667\u20131670 (1997).","journal-title":"Phys. Rev. Lett."},{"key":"21615_CR15","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1126\/science.275.5303.1102","volume":"275","author":"SM Nie","year":"1997","unstructured":"Nie, S. M. & Emery, S. R. Probing single molecules and single nanoparticles by surface-enhanced Raman scattering. Science 275, 1102\u20131106 (1997).","journal-title":"Science"},{"key":"21615_CR16","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S0165-9936(98)00069-7","volume":"17","author":"T Vo-Dinh","year":"1998","unstructured":"Vo-Dinh, T. Surface-enhanced Raman spectroscopy using metallic nanostructures. Trac-Trend. Anal. Chem. 17, 557\u2013582 (1998).","journal-title":"Trac-Trend. Anal. Chem."},{"key":"21615_CR17","doi-asserted-by":"publisher","first-page":"10127","DOI":"10.1039\/c3nr03633b","volume":"5","author":"T Vo-Dinh","year":"2013","unstructured":"Vo-Dinh, T. et al. Plasmonic nanoprobes: from chemical sensing to medical diagnostics and therapy. Nanoscale 5, 10127\u201310140 (2013).","journal-title":"Nanoscale"},{"key":"21615_CR18","doi-asserted-by":"crossref","unstructured":"Dinish, U. S., Balasundaram, G., Chang, Y. T. & Olivo, M. Actively Targeted In Vivo Multiplex Detection of Intrinsic Cancer Biomarkers Using Biocompatible SERS Nanotags. Sci. Rep. 4 (2014).","DOI":"10.1038\/srep04075"},{"key":"21615_CR19","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1021\/ac970901z","volume":"70","author":"NR Isola","year":"1998","unstructured":"Isola, N. R., Stokes, D. L. & Vo-Dinh, T. Surface enhanced Raman gene probe for HIV detection. Anal. Chem. 70, 1352\u20131356 (1998).","journal-title":"Anal. Chem."},{"key":"21615_CR20","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1126\/science.297.5586.1536","volume":"297","author":"YWC Cao","year":"2002","unstructured":"Cao, Y. W. C., Jin, R. C. & Mirkin, C. A. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297, 1536\u20131540 (2002).","journal-title":"Science"},{"key":"21615_CR21","doi-asserted-by":"publisher","first-page":"6086","DOI":"10.1021\/ja0705184","volume":"129","author":"L Fabris","year":"2007","unstructured":"Fabris, L. et al. A heterogeneous PNA-based SERS method for DNA detection. J. Am. Chem. Soc. 129, 6086\u20136087 (2007).","journal-title":"J. Am. Chem. Soc."},{"key":"21615_CR22","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1021\/nl1000086","volume":"10","author":"T Kang","year":"2010","unstructured":"Kang, T., Yoo, S. M., Yoon, I., Lee, S. Y. & Kim, B. Patterned Multiplex Pathogen DNA Detection by Au Particle-on-Wire SERS Sensor. Nano Lett. 10, 1189\u20131193 (2010).","journal-title":"Nano Lett."},{"key":"21615_CR23","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1039\/b920358c","volume":"135","author":"J Hu","year":"2010","unstructured":"Hu, J. et al. Sub-attomolar HIV-1 DNA detection using surface-enhanced Raman spectroscopy. Analyst 135, 1084\u20131089 (2010).","journal-title":"Analyst"},{"key":"21615_CR24","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.nantod.2011.02.004","volume":"6","author":"Y He","year":"2011","unstructured":"He, Y. et al. Silicon nanowires-based highly-efficient SERS-active platform for ultrasensitive DNA detection. Nano Today 6, 122\u2013130 (2011).","journal-title":"Nano Today"},{"key":"21615_CR25","doi-asserted-by":"publisher","first-page":"7407","DOI":"10.1039\/c1cc11062d","volume":"47","author":"ZL Zhang","year":"2011","unstructured":"Zhang, Z. L. et al. Mixed DNA-functionalized nanoparticle probes for surface-enhanced Raman scattering-based multiplex DNA detection. Chem Commun 47, 7407\u20137409 (2011).","journal-title":"Chem Commun"},{"key":"21615_CR26","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1039\/c2an35112a","volume":"137","author":"MM Harper","year":"2012","unstructured":"Harper, M. M., Dougan, J. A., Shand, N. C., Graham, D. & Faulds, K. Detection of SERS active labelled DNA based on surface affinity to silver nanoparticles. Analyst 137, 2063\u20132068 (2012).","journal-title":"Analyst"},{"key":"21615_CR27","doi-asserted-by":"publisher","first-page":"4030","DOI":"10.1021\/la204890t","volume":"28","author":"H Zhang","year":"2012","unstructured":"Zhang, H., Harpster, M. H., Wilson, W. C. & Johnson, P. A. Surface-Enhanced Raman Scattering Detection of DNAs Derived from Virus Genomes Using Au-Coated Paramagnetic Nanoparticles. Langmuir 28, 4030\u20134037 (2012).","journal-title":"Langmuir"},{"key":"21615_CR28","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1021\/ac302254h","volume":"85","author":"D van Lierop","year":"2013","unstructured":"van Lierop, D., Larmour, I. A., Faulds, K. & Graham, D. SERS Primers and Their Mode of Action for Pathogen DNA Detection. Anal. Chem. 85, 1408\u20131414 (2013).","journal-title":"Anal. Chem."},{"key":"21615_CR29","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1002\/smll.201202914","volume":"9","author":"X Wei","year":"2013","unstructured":"Wei, X. et al. A Molecular Beacon-Based Signal-Off Surface-Enhanced Raman Scattering Strategy for Highly Sensitive, Reproducible, and Multiplexed DNA Detection. Small 9, 2493\u20132499 (2013).","journal-title":"Small"},{"key":"21615_CR30","doi-asserted-by":"publisher","first-page":"6147","DOI":"10.1021\/la4006828","volume":"29","author":"J-M Li","year":"2013","unstructured":"Li, J.-M. et al. Highly Sensitive Detection of Target ssDNA Based on SERS Liquid Chip Using Suspended Magnetic Nanospheres as Capturing Substrates. Langmuir 29, 6147\u20136155 (2013).","journal-title":"Langmuir"},{"key":"21615_CR31","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1021\/ac303387a","volume":"85","author":"M Li","year":"2013","unstructured":"Li, M. et al. Plasmonic Nanorice Antenna on Triangle Nanoarray for Surface-Enhanced Raman Scattering Detection of Hepatitis B Virus DNA. Anal. Chem. 85, 2072\u20132078 (2013).","journal-title":"Anal. Chem."},{"key":"21615_CR32","doi-asserted-by":"publisher","first-page":"8521","DOI":"10.1039\/C4NR01951B","volume":"6","author":"J Qi","year":"2014","unstructured":"Qi, J. et al. Label-free, in situ SERS monitoring of individual DNA hybridization in microfluidics. Nanoscale 6, 8521\u20138526 (2014).","journal-title":"Nanoscale"},{"key":"21615_CR33","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1039\/C4AY00155A","volume":"6","author":"S Hibbitts","year":"2014","unstructured":"Hibbitts, S. et al. Human papilloma virus genotyping by surface-enhanced Raman scattering. Analytical Methods 6, 1288\u20131290 (2014).","journal-title":"Analytical Methods"},{"key":"21615_CR34","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1021\/acs.analchem.6b04729","volume":"89","author":"J Su","year":"2017","unstructured":"Su, J. et al. Multicolor Gold Silver Nano-Mushrooms as Ready-to-Use SERS Probes for Ultrasensitive and Multiplex DNA\/miRNA Detection. Anal. Chem. 89, 2531\u20132538 (2017).","journal-title":"Anal. Chem."},{"key":"21615_CR35","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.bios.2015.12.052","volume":"79","author":"Y Pang","year":"2016","unstructured":"Pang, Y. et al. Fe3O4@Ag magnetic nanoparticles for microRNA capture and duplex-specific nuclease signal amplification based SERS detection in cancer cells. Biosens. Bioelectron. 79, 574\u2013580 (2016).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR36","doi-asserted-by":"publisher","first-page":"11684","DOI":"10.1021\/acs.analchem.6b03267","volume":"88","author":"YY Li","year":"2016","unstructured":"Li, Y. Y. et al. Ultrasensitive Signal-On Detection of Nucleic Acids with Surface-Enhanced Raman Scattering and Exonuclease III-Assisted Probe Amplification. Anal. Chem. 88, 11684\u201311690 (2016).","journal-title":"Anal. Chem."},{"key":"21615_CR37","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.bios.2015.11.099","volume":"78","author":"X Fu","year":"2016","unstructured":"Fu, X. et al. A SERS-based lateral flow assay biosensor for highly sensitive detection of HIV-1DNA. Biosens. Bioelectron. 78, 530\u2013537 (2016).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR38","doi-asserted-by":"publisher","first-page":"6378","DOI":"10.1021\/ac400763c","volume":"85","author":"HT Ngo","year":"2013","unstructured":"Ngo, H. T., Wang, H. N., Fales, A. M. & Vo-Dinh, T. Label-Free DNA Biosensor Based on SERS Molecular Sentinel on Nanowave Chip. Anal. Chem. 85, 6378\u20136383 (2013).","journal-title":"Anal. Chem."},{"key":"21615_CR39","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1007\/s00216-014-7648-4","volume":"406","author":"H Ngo","year":"2014","unstructured":"Ngo, H., Wang, H.-N., Burke, T., Ginsburg, G. & Vo-Dinh, T. Multiplex detection of disease biomarkers using SERS molecular sentinel-on-chip. Anal. Bioanal. Chem. 406, 3335\u20133344 (2014).","journal-title":"Anal. Bioanal. Chem."},{"key":"21615_CR40","doi-asserted-by":"publisher","first-page":"5655","DOI":"10.1039\/C4AN01077A","volume":"139","author":"HT Ngo","year":"2014","unstructured":"Ngo, H. T. et al. DNA bioassay-on-chip using SERS detection for dengue diagnosis. Analyst 139, 5655\u20135659 (2014).","journal-title":"Analyst"},{"key":"21615_CR41","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1039\/C5CS00644A","volume":"45","author":"S Laing","year":"2016","unstructured":"Laing, S., Gracie, K. & Faulds, K. Multiplex in vitro detection using SERS. Chemical Society reviews 45, 1901\u20131918 (2016).","journal-title":"Chemical Society reviews"},{"key":"21615_CR42","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1039\/C5TB02135A","volume":"4","author":"J Chao","year":"2016","unstructured":"Chao, J. et al. Nanostructure-based surface-enhanced Raman scattering biosensors for nucleic acids and proteins. J Mater Chem B 4, 1757\u20131769 (2016).","journal-title":"J Mater Chem B"},{"key":"21615_CR43","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1007\/s00216-015-9121-4","volume":"408","author":"HT Ngo","year":"2016","unstructured":"Ngo, H. T., Wang, H. N., Fales, A. M. & Vo-Dinh, T. Plasmonic SERS biosensing nanochips for DNA detection. Anal Bioanal Chem 408, 1773\u20131781 (2016).","journal-title":"Anal Bioanal Chem"},{"key":"21615_CR44","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1021\/ac1023843","volume":"83","author":"H Zhang","year":"2011","unstructured":"Zhang, H., Harpster, M. H., Park, H. J. & Johnson, P. A. Surface-Enhanced Raman Scattering Detection of DNA Derived from the West Nile Virus Genome Using Magnetic Capture of Raman-Active Gold Nanoparticles. Anal. Chem. 83, 254\u2013260 (2011).","journal-title":"Anal. Chem."},{"key":"21615_CR45","doi-asserted-by":"crossref","unstructured":"Xu, H. et al. In Raman Spectroscopy for Nanomaterials Characterization (ed ChallaS S. R. Kumar) Ch. 19, 531-551 (Springer Berlin Heidelberg, 2012).","DOI":"10.1007\/978-3-642-20620-7_19"},{"key":"21615_CR46","doi-asserted-by":"publisher","first-page":"12907","DOI":"10.1039\/C4CC06335J","volume":"50","author":"T Donnelly","year":"2014","unstructured":"Donnelly, T., Smith, W. E., Faulds, K. & Graham, D. Silver and magnetic nanoparticles for sensitive DNA detection by SERS. Chem Commun (Camb) 50, 12907\u201312910 (2014).","journal-title":"Chem Commun (Camb)"},{"key":"21615_CR47","doi-asserted-by":"publisher","first-page":"15284","DOI":"10.1039\/C5CC06571B","volume":"51","author":"JN Zhang","year":"2015","unstructured":"Zhang, J. N., Joshi, P., Zhou, Y., Ding, R. & Zhang, P. Quantitative SERS-based DNA detection assisted by magnetic microspheres. Chem Commun 51, 15284\u201315286 (2015).","journal-title":"Chem Commun"},{"key":"21615_CR48","doi-asserted-by":"crossref","unstructured":"Kahraman, M., Mullen Emma, R., Korkmaz, A. & Wachsmann-Hogiu, S. In Nanophotonics Vol. 6, 831 (2017).","DOI":"10.1515\/nanoph-2016-0174"},{"key":"21615_CR49","doi-asserted-by":"publisher","first-page":"3865","DOI":"10.1039\/C5CS00828J","volume":"45","author":"JH Granger","year":"2016","unstructured":"Granger, J. H., Schlotter, N. E., Crawford, A. C. & Porter, M. D. Prospects for point-of-care pathogen diagnostics using surface-enhanced Raman scattering (SERS). Chemical Society reviews 45, 3865\u20133882 (2016).","journal-title":"Chemical Society reviews"},{"key":"21615_CR50","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.bios.2016.01.073","volume":"81","author":"HT Ngo","year":"2016","unstructured":"Ngo, H. T., Gandra, N., Fales, A. M., Taylor, S. M. & Vo-Dinh, T. Sensitive DNA detection and SNP discrimination using ultrabright SERS nanorattles and magnetic beads for malaria diagnostics. Biosens. Bioelectron. 81, 8\u201314 (2016).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR51","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1021\/acs.analchem.7b00274","volume":"89","author":"IA Nanayakkara","year":"2017","unstructured":"Nanayakkara, I. A., Cao, W. D. & White, I. M. Simplifying Nucleic Acid Amplification from Whole Blood with Direct Polymerase Chain Reaction on Chitosan Microparticles. Anal. Chem. 89, 3773\u20133779 (2017).","journal-title":"Anal. Chem."},{"key":"21615_CR52","doi-asserted-by":"publisher","first-page":"6725","DOI":"10.1021\/nn102237c","volume":"4","author":"YY Ma","year":"2010","unstructured":"Ma, Y. Y. et al. Au@Ag Core-Shell Nanocubes with Finely Tuned and Well-Controlled Sizes, Shell Thicknesses, and Optical Properties. Acs Nano 4, 6725\u20136734 (2010).","journal-title":"Acs Nano"},{"key":"21615_CR53","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1021\/acs.chemmater.5b01401","volume":"27","author":"KK Liu","year":"2015","unstructured":"Liu, K. K., Tadepalli, S., Tian, L. M. & Singamaneni, S. Size-Dependent Surface Enhanced Raman Scattering Activity of Plasmonic Nanorattles. Chem. Mater. 27, 5261\u20135270 (2015).","journal-title":"Chem. Mater."},{"key":"21615_CR54","doi-asserted-by":"publisher","first-page":"6313","DOI":"10.1002\/adma.201302820","volume":"25","author":"XH Xia","year":"2013","unstructured":"Xia, X. H., Wang, Y., Ruditskiy, A. & Xia, Y. N. 25th Anniversary Article: Galvanic Replacement: A Simple and Versatile Route to Hollow Nanostructures with Tunable and Well-Controlled Properties. Adv. Mater. 25, 6313\u20136333 (2013).","journal-title":"Adv. Mater."},{"key":"21615_CR55","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1002\/adma.201203415","volume":"25","author":"N Gandra","year":"2013","unstructured":"Gandra, N. & Singamaneni, S. Bilayered Raman-Intense Gold Nanostructures with Hidden Tags (BRIGHTs) for High-Resolution Bioimaging. Adv. Mater. 25, 1022\u20131027 (2013).","journal-title":"Adv. Mater."},{"key":"21615_CR56","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1021\/ar800018v","volume":"41","author":"SE Skrabalak","year":"2008","unstructured":"Skrabalak, S. E. et al. Gold Nanocages: Synthesis, Properties, and Applications. Accounts Chem Res 41, 1587\u20131595 (2008).","journal-title":"Accounts Chem Res"},{"key":"21615_CR57","doi-asserted-by":"publisher","first-page":"8486","DOI":"10.1039\/C5NR08980H","volume":"8","author":"N Gandra","year":"2016","unstructured":"Gandra, N. et al. Tunable and amplified Raman gold nanoprobes for effective tracking (TARGET): in vivo sensing and imaging. Nanoscale 8, 8486\u20138494 (2016).","journal-title":"Nanoscale"},{"key":"21615_CR58","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1039\/C3SC52875H","volume":"5","author":"K Gracie","year":"2014","unstructured":"Gracie, K. et al. Simultaneous detection and quantification of three bacterial meningitis pathogens by SERS. Chem Sci 5, 1030\u20131040 (2014).","journal-title":"Chem Sci"},{"key":"21615_CR59","doi-asserted-by":"publisher","first-page":"4762","DOI":"10.1021\/ja200894u","volume":"133","author":"GD Moon","year":"2011","unstructured":"Moon, G. D. et al. A New Theranostic System Based on Gold Nanocages and Phase-Change Materials with Unique Features for Photoacoustic Imaging and Controlled Release. J. Am. Chem. Soc. 133, 4762\u20134765 (2011).","journal-title":"J. Am. Chem. Soc."},{"key":"21615_CR60","doi-asserted-by":"crossref","unstructured":"Creecy, A., Russ, P. K., Solinas, F., Wright, D. W. & Haselton, F. R. Tuberculosis Biomarker Extraction and Isothermal Amplification in an Integrated Diagnostic Device. Plos One 10 (2015).","DOI":"10.1371\/journal.pone.0130260"},{"key":"21615_CR61","doi-asserted-by":"crossref","unstructured":"Scherr, T. F., Ryskoski, H. B., Doyle, A. B. & Haselton, F. R. A two-magnet strategy for improved mixing and capture from biofluids. Biomicrofluidics 10 (2016).","DOI":"10.1063\/1.4946014"},{"key":"21615_CR62","doi-asserted-by":"crossref","unstructured":"Adams, N. M. et al. Design criteria for developing low-resource magnetic bead assays using surface tension valves. Biomicrofluidics 7 (2013).","DOI":"10.1063\/1.4788922"},{"key":"21615_CR63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.aca.2015.10.011","volume":"906","author":"A Yamaguchi","year":"2016","unstructured":"Yamaguchi, A., Matsuda, K., Uehara, M., Honda, T. & Saito, Y. A novel automated device for rapid nucleic acid extraction utilizing a zigzag motion of magnetic silica beads. Anal Chim Acta 906, 1\u20136 (2016).","journal-title":"Anal Chim Acta"},{"key":"21615_CR64","doi-asserted-by":"publisher","first-page":"371","DOI":"10.2116\/analsci.32.371","volume":"32","author":"M Uehara","year":"2016","unstructured":"Uehara, M. et al. A Rapid and Automated Device for Purifying Nucleic Acids. Analytical Sciences 32, 371\u2013374 (2016).","journal-title":"Analytical Sciences"},{"key":"21615_CR65","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s00542-013-1798-8","volume":"20","author":"M Shikida","year":"2014","unstructured":"Shikida, M., Sugito, T., Okochi, M. & Honda, H. Droplet-based biochemical assay by magnetic wire manipulation between multiple droplets. Microsyst Technol 20, 315\u2013323 (2014).","journal-title":"Microsyst Technol"},{"key":"21615_CR66","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s10544-013-9816-2","volume":"16","author":"R Gottheil","year":"2014","unstructured":"Gottheil, R. et al. Moving the solid phase: a platform technology for cartridge based sandwich immunoassays. Biomed Microdevices 16, 163\u2013172 (2014).","journal-title":"Biomed Microdevices"},{"key":"21615_CR67","doi-asserted-by":"crossref","unstructured":"Wang, S. Q. et al. Micro-a-fluidics ELISA for Rapid CD4 Cell Count at the Point-of-Care. Sci. Rep. 4 (2014).","DOI":"10.1038\/srep03796"},{"key":"21615_CR68","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.bios.2013.06.011","volume":"50","author":"CH Chiou","year":"2013","unstructured":"Chiou, C. H., Shin, D. J., Zhang, Y. & Wang, T. H. Topography-assisted electromagnetic platform for blood-to-PCR in a droplet. Biosens. Bioelectron. 50, 91\u201399 (2013).","journal-title":"Biosens. Bioelectron."},{"key":"21615_CR69","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1365-2958.2009.07026.x","volume":"76","author":"TD Otto","year":"2010","unstructured":"Otto, T. D. et al. New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq. Mol Microbiol 76, 12\u201324 (2010).","journal-title":"Mol Microbiol"},{"key":"21615_CR70","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","volume":"193","author":"W Trager","year":"1976","unstructured":"Trager, W. & Jensen, J. B. Human Malaria Parasites in Continuous Culture. Science 193, 673\u2013675 (1976).","journal-title":"Science"},{"key":"21615_CR71","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nprot.2006.51","volume":"1","author":"HD Hill","year":"2006","unstructured":"Hill, H. D. & Mirkin, C. A. The bio-barcode assay for the detection of protein and nucleic acid targets using DTT-induced ligand exchange. Nat Protoc 1, 324\u2013336 (2006).","journal-title":"Nat Protoc"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-21615-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-21615-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-21615-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T03:06:25Z","timestamp":1671591985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-21615-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,6]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["21615"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-21615-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,6]]},"assertion":[{"value":"6 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4075"}}