{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:37:41Z","timestamp":1776213461017,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T00:00:00Z","timestamp":1466726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The objective of this paper is to report a novel non-invasive, real-time, and label-free smart assay technique for the prognostic detection of bone loss by electrochemical impedance spectroscopy (EIS). The proposed system incorporated an antibody-antigen-based sensor functionalization to induce selectivity for the C-terminal telopeptide type one collagen (CTx-I) molecules\u2014a bone loss biomarker. Streptavidin agarose was immobilized on the sensing area of a silicon substrate-based planar sensor, patterned with gold interdigital electrodes, to capture the antibody-antigen complex. Calibration experiments were conducted with various known CTx-I concentrations in a buffer solution to obtain a reference curve that was used to quantify the concentration of an analyte in the unknown serum samples. Multivariate chemometric analyses were done to determine the performance viability of the developed system. The analyses suggested that a frequency of 710 Hz is the most discriminating regarding the system sensitivity. A detection limit of 0.147 ng\/mL was achieved for the proposed sensor and the corresponding reference curve was linear in the range of 0.147 ng\/mL to 2.669 ng\/mL. Two sheep blood samples were tested by the developed technique and the results were validated using enzyme-linked immunosorbent assay (ELISA). The results from the proposed technique match those from the ELISA.<\/jats:p>","DOI":"10.3390\/s16070976","type":"journal-article","created":{"date-parts":[[2016,6,25]],"date-time":"2016-06-25T21:21:45Z","timestamp":1466889705000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Smart Sensing System for the Prognostic Monitoring of Bone Health"],"prefix":"10.3390","volume":"16","author":[{"given":"Nasrin","family":"Afsarimanesh","sequence":"first","affiliation":[{"name":"School of Engineering and Advanced Technology, Massey University, Palmerston North 4442, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asif","family":"Zia","sequence":"additional","affiliation":[{"name":"School of Engineering and Advanced Technology, Massey University, Palmerston North 4442, New Zealand"},{"name":"Department of Physics, COMSATS Institute of Science and Technology, Islamabad 45550, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhas","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Engineering, Macquarie University, North Ryde NSW 2109, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8646-9672","authenticated-orcid":false,"given":"Marlena","family":"Kruger","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Massey University, Palmerston North 4442, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pak-Lam","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Engineering and Advanced Technology, Massey University, Palmerston North 4442, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgen","family":"Kosel","sequence":"additional","affiliation":[{"name":"Sensing, Magnetism and Microsystems Group, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoltan","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Physics and Control, Faculty of Food Science, Szent Istv\u00e1n University, Budapest H-1118, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,24]]},"reference":[{"key":"ref_1","unstructured":"Seibel, M.J., Robins, S.P., and Bilezikian, J.P. (2006). Dynamics of Bone and Cartilage Metabolism: Principles and Clinical Applications, Academic Press."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Seeman, E. (2004). Osteoporosis in Men: The \u201cSilent Epidemic\u201d Strikes Men Too, International Osteoporosis Foundation.","DOI":"10.1007\/978-0-85729-402-9_20"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1080\/20786204.2014.932549","article-title":"Menopause-related osteoporosis","volume":"56","author":"Snyman","year":"2014","journal-title":"S. Afr. Fam. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/S1701-2163(15)30489-8","article-title":"Osteoporosis in menopause","volume":"36","author":"Khan","year":"2014","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1359\/jbmr.2005.20.5.886","article-title":"How many women have osteoporosis?","volume":"20","author":"Melton","year":"2005","journal-title":"J. Bone Min. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s001980070064","article-title":"Long-term risk of osteoporotic fracture in malm\u00f6","volume":"11","author":"Kanis","year":"2000","journal-title":"Osteoporos. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00223-001-1034-x","article-title":"A new monoclonal antibody elisa for detection and characterization of C-telopeptide fragments of type I collagen in urine","volume":"69","author":"Srivastava","year":"2001","journal-title":"Calcif. Tissue Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1503\/cmaj.100771","article-title":"2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: Summary","volume":"182","author":"Papaioannou","year":"2010","journal-title":"Can. Med. Assoc. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s00198-008-0660-9","article-title":"Biochemical markers of bone turnover: Potential use in the investigation and management of postmenopausal osteoporosis","volume":"19","author":"Szulc","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/smll.200901551","article-title":"A nanoelectronic enzyme-linked immunosorbent assay for detection of proteins in physiological solutions","volume":"6","author":"Stern","year":"2010","journal-title":"Small"},{"key":"ref_11","unstructured":"Paulie, S., and Perlmann, H. (2016). eLS, John Wiley & Sons Ltd."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1038\/jid.2013.287","article-title":"Enzyme immunoassay and enzyme-linked immunosorbent assay","volume":"133","author":"Gan","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0009-9120(97)00113-6","article-title":"Biochemical markers of bone metabolism: An overview","volume":"30","author":"Christenson","year":"1997","journal-title":"Clin. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2528\/PIERB08022901","article-title":"Capacitive interdigital sensor with inhomogeneous nematic liquid crystal film","volume":"7","author":"Lindquist","year":"2008","journal-title":"Prog. Electromagn. Res. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1109\/JPROC.2004.826603","article-title":"Interdigital sensors and transducers","volume":"92","author":"Mamishev","year":"2004","journal-title":"Proc. IEEE"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.snb.2008.12.053","article-title":"A low cost novel sensing system for detection of dangerous marine biotoxins in seafood","volume":"137","author":"Syaifudin","year":"2009","journal-title":"Sens. Actuators B Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Syaifudin, A.M., Mukhopadhyay, S., and Yu, P. (2009, January 14\u201316). Electromagnetic field computation using comsol multiphysics to evaluate the performance of novel interdigital sensors. Proceedings of the Applied Electromagnetics Conference (AEMC), Kolkata, India.","DOI":"10.1109\/AEMC.2009.5430661"},{"key":"ref_18","unstructured":"Syaifudin, A.M., Yunus, M., Mukhopadhyay, S., and Jayasundera, K. (2009, January 25\u201328). A novel planar interdigital sensor for environmental monitoring. Proceedings of the 2009 IEEE Sensors, Christchurch, New Zealand."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.bios.2012.07.034","article-title":"Nanowires array modified electrode for enhanced electrochemical detection of nucleic acid","volume":"40","author":"Ramulu","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.bios.2014.08.050","article-title":"Rapid and molecular selective electrochemical sensing of phthalates in aqueous solution","volume":"67","author":"Zia","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bios.2014.10.017","article-title":"A new aptamer\/graphene interdigitated gold electrode piezoelectric sensor for rapid and specific detection of staphylococcus aureus","volume":"65","author":"Lian","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_22","unstructured":"Syaifudin, A., Jayasundera, K., and Mukhopadhyay, S. (2009, January 5\u20137). A novel planar interdigital sensor based sensing and instrumentation for detection of dangerous contaminated chemical in seafood. Proceedings of the IEEE Instrumentation and Measurement Technology Conference, I2MTC\u203209, Singapore."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.bios.2015.10.014","article-title":"Gold-coated carbon nanotube electrode arrays: Immunosensors for impedimetric detection of bone biomarkers","volume":"77","author":"Ramanathan","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_24","unstructured":"Buller, S., Karden, E., Kok, D., and Doncker, R.W.D. (October, January 30). Modeling the dynamic behavior of supercapacitors using impedance spectroscopy. Proceedings of the IEEE Thirty-Sixth IAS Annual Meeting, Chicago, IL, USA."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1109\/TIE.2010.2048832","article-title":"Study of accelerated aging of supercapacitors for transport applications","volume":"57","author":"Hammar","year":"2010","journal-title":"IEEE Trans. Ind. Electron."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.electacta.2013.11.154","article-title":"Corrosion behavior of stainless steel rebars embedded in concrete: An electrochemical impedance spectroscopy study","volume":"124","author":"Duarte","year":"2014","journal-title":"Electrochim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.foodchem.2014.12.030","article-title":"Highly sensitive electrochemical impedance spectroscopy immunosensor for the detection of AFB 1 in olive oil","volume":"176","author":"Yu","year":"2015","journal-title":"Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bios.2012.11.028","article-title":"Label-free electrochemical impedance spectroscopy biosensor for direct detection of cancer cells based on the interaction between carbohydrate and lectin","volume":"43","author":"Hu","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.bios.2012.07.052","article-title":"Electrochemical impedance spectroscopy biosensor with interdigitated electrode for detection of human immunoglobulin A","volume":"40","author":"Ohno","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1109\/JSEN.2007.903335","article-title":"A novel planar-type biosensor for noninvasive meat inspection","volume":"7","author":"Mukhopadhyay","year":"2007","journal-title":"IEEE Sens. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.jfoodeng.2012.08.026","article-title":"Detection of bacterial endotoxin in food: New planar interdigital sensors based approach","volume":"114","author":"Rahman","year":"2013","journal-title":"J. Food Eng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.jfoodeng.2011.03.023","article-title":"Coagulation process of soymilk characterized by electrical impedance spectroscopy","volume":"105","author":"Li","year":"2011","journal-title":"J. Food Eng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.3390\/s91007957","article-title":"A label-free electronic biosensor for detection of bone turnover markers","volume":"9","author":"Yun","year":"2009","journal-title":"Sensors"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.3390\/s130404811","article-title":"Immobilization techniques in the fabrication of nanomaterial-based electrochemical biosensors: A review","volume":"13","author":"Putzbach","year":"2013","journal-title":"Sensors"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1109\/TIM.2009.2012957","article-title":"Capacitive-sensor interface with high accuracy and stability","volume":"58","author":"Nojdelov","year":"2009","journal-title":"IEEE Trans. Instrum. Meas."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"747","DOI":"10.5006\/1.3280607","article-title":"Technical note: Concerning the conversion of the constant phase element parameter Y0 into a capacitance","volume":"57","author":"Hsu","year":"2001","journal-title":"Corrosion"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/16\/7\/976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:24:46Z","timestamp":1760210686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/16\/7\/976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,24]]},"references-count":36,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7]]}},"alternative-id":["s16070976"],"URL":"https:\/\/doi.org\/10.3390\/s16070976","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,24]]}}}