{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:26:36Z","timestamp":1770960396523,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["NSC 95-3114-P-194-001-MY3, NSC 94-2320-B-303 -004"],"award-info":[{"award-number":["NSC 95-3114-P-194-001-MY3, NSC 94-2320-B-303 -004"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-\u03bcL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance.<\/jats:p>","DOI":"10.3390\/s20113137","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"3137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis"],"prefix":"10.3390","volume":"20","author":[{"given":"Yen-Ta","family":"Tseng","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry and Center for Nano Bio-Detection, National Chung Cheng University, Chiayi 62102, Taiwan"}]},{"given":"Wan-Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and Center for Nano Bio-Detection, National Chung Cheng University, Chiayi 62102, Taiwan"}]},{"given":"Ya-Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and Center for Nano Bio-Detection, National Chung Cheng University, Chiayi 62102, Taiwan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0839-7538","authenticated-orcid":false,"given":"Chang-Yue","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and Center for Nano Bio-Detection, National Chung Cheng University, Chiayi 62102, Taiwan"},{"name":"Graduate School of Engineering Science and Technology, National Yunlin University of Science and Technology, Yunlin 64002, Taiwan"}]},{"given":"Su-Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"Immunology and Rheumatology, Department of Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi 62247, Taiwan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1659-6465","authenticated-orcid":false,"given":"Lai-Kwan","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and Center for Nano Bio-Detection, National Chung Cheng University, Chiayi 62102, Taiwan"}]},{"given":"Ning-Sheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Immunology and Rheumatology, Department of Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi 62247, Taiwan"}]},{"given":"Cheng-Chung","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, National Chung Cheng University, Chiayi 62102, Taiwan"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1093\/nar\/28.16.3011","article-title":"SURVEY AND SUMMARY: From DNA biosensors to gene chips","volume":"28","author":"Wang","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_2","first-page":"122","article-title":"Recent advances in DNA biosensor","volume":"92","author":"Kumar","year":"2008","journal-title":"Sens. Transducer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.bios.2008.08.012","article-title":"High-throughput SPR sensor for food safety","volume":"24","author":"Piliarik","year":"2009","journal-title":"Biosens. Bioelectron."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12043","DOI":"10.1039\/c3nr02257a","article-title":"Localized surface plasmon resonance: A unique property of plasmonic nanoparticles for nucleic acid detection","volume":"5","author":"Fong","year":"2013","journal-title":"Nanoscale"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.aca.2013.10.048","article-title":"Trends and challenges of refractometric nanoplasmonic biosensors: A review","volume":"806","author":"Estevez","year":"2014","journal-title":"Anal. Chim. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1021\/cr4000623","article-title":"Advances in plasmonic technologies for point of care applications","volume":"114","author":"Tokel","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1021\/cr100313v","article-title":"Localized surface plasmon resonance sensors","volume":"111","author":"Mayer","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1021\/ac020310v","article-title":"Colloidal gold-modified optical fiber for chemical and biochemical sensing","volume":"75","author":"Cheng","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wu, W.-T., Chen, C.-H., Chiang, C.-Y., and Chau, L.-K. (2018). Effect of surface coverage of gold nanoparticles on the refractive index sensitivity in fiber-optic nanoplasmonic sensing. Sensors, 18.","DOI":"10.3390\/s18061759"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.aca.2011.04.023","article-title":"Integration of fiber optic-particle plasmon resonance biosensor with microfluidic chip","volume":"697","author":"Hsu","year":"2011","journal-title":"Anal. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00216-007-1276-1","article-title":"Detection of antinuclear antibodies by a colloidal gold modified optical fiber: Comparison with ELISA","volume":"388","author":"Lai","year":"2007","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.bios.2010.08.047","article-title":"Fiber-optic particle plasmon resonance sensor for detection of interleukin-1\u03b2 in synovial fluids","volume":"26","author":"Chiang","year":"2010","journal-title":"Biosens. Bioelectron."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4599","DOI":"10.1039\/c3an00276d","article-title":"Quantification of tumor necrosis factor-\u03b1 and matrix metalloproteinases-3 in synovial fluid by a fiber-optic particle plasmon resonance sensor","volume":"138","author":"Huang","year":"2013","journal-title":"Analyst"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.bios.2013.08.009","article-title":"Direct detection of orchid viruses using nanorod-based fiber optic particle plasmon resonance immunosensor","volume":"51","author":"Lin","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111871","DOI":"10.1016\/j.bios.2019.111871","article-title":"Fiber optic nanogold-linked immunosorbent assay for rapid detection of procalcitonin at femtomolar concentration level","volume":"151","author":"Chiang","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.snb.2005.02.034","article-title":"Fiber-optic chemical and biochemical probes based on localized surface plasmon resonance","volume":"113","author":"Chau","year":"2006","journal-title":"Sens. Actuators B: Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1016\/j.bios.2009.02.007","article-title":"Novel U-bent fiber optic probe for localized surface plasmon resonance based biosensor","volume":"24","author":"Sai","year":"2009","journal-title":"Biosens. Bioelectron."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/jccs.201190122","article-title":"A fiber optic particle plasmon resonance biosensing platform based on detection of light scattering intensity from the proximal end","volume":"58","author":"Chau","year":"2011","journal-title":"J. Chin. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.snb.2013.02.052","article-title":"Wavelength-based localized surface plasmon resonance optical fiber biosensor","volume":"181","author":"Cao","year":"2013","journal-title":"Sens. Actuators B: Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.colsurfa.2015.11.025","article-title":"Developing localized surface plasmon resonance biosensor chips and fiber optics via direct surface modification of PMMA optical waveguides","volume":"492","author":"Jin","year":"2016","journal-title":"Colloids Surf. A: Physicochem. Eng. Asp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.bios.2017.11.062","article-title":"An optical fiber-based LSPR aptasensor for simple and rapid in-situ detection of ochratoxin A","volume":"102","author":"Lee","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.snb.2012.01.037","article-title":"Improved performance of aminopropylsilatrane over aminopropyltriethoxysilane as a linker for nanoparticle-based plasmon resonance sensors","volume":"163","author":"Huang","year":"2012","journal-title":"Sens. Actuators B Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.talanta.2015.08.047","article-title":"Self-referencing fiber optic particle plasmon resonance sensing system for real-time biological monitoring","volume":"146","author":"Wu","year":"2016","journal-title":"Talanta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/cei.13020","article-title":"The interplay between HLA-B27 and ERAP1\/ERAP2 aminopeptidases: From anti-viral protection to spondyloarthritis","volume":"190","author":"Vitulano","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_25","first-page":"1128","article-title":"Quantitative measurement of HLA-B27 mRNA in patients with ankylosing spondylitis\u2014Correlation with clinical activity","volume":"33","author":"Liu","year":"2006","journal-title":"J. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/rheumatology\/41.12.1375","article-title":"Increased level of HLA-B27 expression in ankylosing spondylitis patients compared with healthy HLA-B27-positive subjects: A possible further susceptibility factor for the development of disease","volume":"41","author":"Cauli","year":"2002","journal-title":"Rheumatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-immunol-032414-112110","article-title":"HLA-B27","volume":"33","author":"Bowness","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0927-7757(00)00832-3","article-title":"Preparation of colloidal gold multilayers with 3-(mercaptopropyl)-trimethoxysilane as a linker molecule","volume":"182","author":"Tseng","year":"2001","journal-title":"Colloids Surf. A: Physicochem. Eng. Asp."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1021\/ac302590n","article-title":"Using a fiber optic particle plasmon resonance biosensor to determine kinetic constants of antigen\u2013antibody binding reaction","volume":"85","author":"Chang","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/nbt0993-1026","article-title":"Kinetic PCR analysis: Real-time monitoring of DNA amplification reactions","volume":"11","author":"Higuchi","year":"1993","journal-title":"Nat. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S1525-1578(10)60652-6","article-title":"A Novel Method to Compensate for Different Amplification Efficiencies between Patient DNA Samples in Quantitative Real-Time PCR","volume":"3","author":"Meijerink","year":"2001","journal-title":"J. Mol. Diagn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1039\/c4an00280f","article-title":"Size-fitting effect for hybridization of DNA\/mercaptohexanol mixed monolayers on gold","volume":"139","author":"Li","year":"2014","journal-title":"Analyst"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8916","DOI":"10.1021\/ja9719586","article-title":"Characterization of DNA probes immobilized on gold surfaces","volume":"119","author":"Herne","year":"1997","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9787","DOI":"10.1021\/ja981897r","article-title":"Using self-assembly to control the structure of DNA monolayers on gold: A neutron reflectivity study","volume":"120","author":"Levicky","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1021\/ac0006627","article-title":"A Fluorescence-Based Method for Determining the Surface Coverage and Hybridization Efficiency of Thiol-Capped Oligonucleotides Bound to Gold Thin Films and Nanoparticles","volume":"72","author":"Demers","year":"2000","journal-title":"Anal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6957","DOI":"10.1021\/la050725m","article-title":"DNA recognition interfaces: The influence of interfacial design on the efficiency and kinetics of hybridization","volume":"21","author":"Wong","year":"2005","journal-title":"Langmuir"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1021\/ja9930824","article-title":"Quantitative measurements and modeling of kinetics in nucleic acid monolayer films using SPR spectroscopy","volume":"122","author":"Georgiadis","year":"2000","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5054","DOI":"10.1021\/ac990561c","article-title":"A fiber-optic evanescent wave DNA biosensor based on novel molecular beacons","volume":"71","author":"Liu","year":"1999","journal-title":"Anal. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nchem.1246","article-title":"Optimizing the specificity of nucleic acid hybridization","volume":"4","author":"Zhang","year":"2012","journal-title":"Nat. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1093\/nar\/gnh067","article-title":"Oligonucleotide hybridization studied by a surface plasmon diffraction sensor (SPDS)","volume":"32","author":"Yu","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1073\/pnas.0709416105","article-title":"DNA surface hybridization regimes","volume":"105","author":"Gong","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.snb.2012.05.023","article-title":"DNA hybridization mechanism in an interfacial environment: What hides beneath first order k (s\u22121) kinetic constant?","volume":"171\u2013172","author":"Lazerges","year":"2012","journal-title":"Sens. Actuators B Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.tibtech.2005.01.004","article-title":"Physicochemical perspectives on DNA microarray and biosensor technologies","volume":"23","author":"Levicky","year":"2005","journal-title":"Trends Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.bpc.2007.09.007","article-title":"Thermodynamic dependence of DNA\/DNA and DNA\/RNA hybridization reactions on temperature and ionic strength","volume":"131","author":"Lang","year":"2007","journal-title":"Biophys. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/S0140-6736(73)91360-3","article-title":"Ankylosing spondylitis and HL-A 27","volume":"301","author":"Brewerton","year":"1973","journal-title":"Lancet"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/20\/11\/3137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:34:47Z","timestamp":1760175287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/20\/11\/3137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["s20113137"],"URL":"https:\/\/doi.org\/10.3390\/s20113137","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]}}}