{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T23:10:32Z","timestamp":1772838632570,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010667","name":"H2020 Industrial Leadership","doi-asserted-by":"publisher","award":["732309"],"award-info":[{"award-number":["732309"]}],"id":[{"id":"10.13039\/100010667","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>In this paper, we present the development of a photonic biosensor device for cancer treatment monitoring as a complementary diagnostics tool. The proposed device combines multidisciplinary concepts from the photonic, nano-biochemical, micro-fluidic and reader\/packaging platforms aiming to overcome limitations related to detection reliability, sensitivity, specificity, compactness and cost issues. The photonic sensor is based on an array of six asymmetric Mach Zender Interferometer (aMZI) waveguides on silicon nitride substrates and the sensing is performed by measuring the phase shift of the output signal, caused by the binding of the analyte on the functionalized aMZI surface. According to the morphological design of the waveguides, an improved sensitivity is achieved in comparison to the current technologies (&lt;5000 nm\/RIU). This platform is combined with a novel biofunctionalization methodology that involves material-selective surface chemistries and the high-resolution laser printing of biomaterials resulting in the development of an integrated photonics biosensor device that employs disposable microfluidics cartridges. The device is tested with cancer patient blood serum samples. The detection of periostin (POSTN) and transforming growth factor beta-induced protein (TGFBI), two circulating biomarkers overexpressed by cancer stem cells, is achieved in cancer patient serum with the use of the device.<\/jats:p>","DOI":"10.3390\/s21062230","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T23:59:41Z","timestamp":1616543981000},"page":"2230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Miniature Bio-Photonics Companion Diagnostics Platform for Reliable Cancer Treatment Monitoring in Blood Fluids"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-4394","authenticated-orcid":false,"given":"Marianneza","family":"Chatzipetrou","sequence":"first","affiliation":[{"name":"Institute of Communication and Computer Systems (ICCS), National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2525-1565","authenticated-orcid":false,"given":"Lefteris","family":"Gounaridis","sequence":"additional","affiliation":[{"name":"Institute of Communication and Computer Systems (ICCS), National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-1074","authenticated-orcid":false,"given":"George","family":"Tsekenis","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation of the Academy of Athens, Soranou Ephessiou 4, 11527 Athens, Greece"}]},{"given":"Maria","family":"Dimadi","sequence":"additional","affiliation":[{"name":"Institute of Communication and Computer Systems (ICCS), National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}]},{"given":"Rachel","family":"Vestering-Stenger","sequence":"additional","affiliation":[{"name":"Future Diagnostic Solutions B.V., Nieuweweg 279, 6603 BN Wijchen, The Netherlands"}]},{"given":"Erik","family":"F. Schreuder","sequence":"additional","affiliation":[{"name":"LioniX International B.V., P.O. Box 456, 7500 AL Enschede, The Netherlands"}]},{"given":"Anke","family":"Trilling","sequence":"additional","affiliation":[{"name":"SurfiX B.V., Plus Ultra Building\u2014Bronland 12 B-1, 6708 WH Wageningen, The Netherlands"}]},{"given":"Geert","family":"Besselink","sequence":"additional","affiliation":[{"name":"LioniX International B.V., P.O. Box 456, 7500 AL Enschede, The Netherlands"}]},{"given":"Luc","family":"Scheres","sequence":"additional","affiliation":[{"name":"SurfiX B.V., Plus Ultra Building\u2014Bronland 12 B-1, 6708 WH Wageningen, The Netherlands"}]},{"given":"Adriaan","family":"van der Meer","sequence":"additional","affiliation":[{"name":"SurfiX B.V., Plus Ultra Building\u2014Bronland 12 B-1, 6708 WH Wageningen, The Netherlands"}]},{"given":"Ernst","family":"Lindhout","sequence":"additional","affiliation":[{"name":"Future Diagnostic Solutions B.V., Nieuweweg 279, 6603 BN Wijchen, The Netherlands"}]},{"given":"Rene","family":"G. Heideman","sequence":"additional","affiliation":[{"name":"LioniX International B.V., P.O. Box 456, 7500 AL Enschede, The Netherlands"}]},{"given":"Henk","family":"Leeuwis","sequence":"additional","affiliation":[{"name":"LioniX International B.V., P.O. Box 456, 7500 AL Enschede, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-0234","authenticated-orcid":false,"given":"Siegfried","family":"Graf","sequence":"additional","affiliation":[{"name":"CSEM SA, Untere Gr\u00fcndlistrasse 1, 6055 Alpnach, Switzerland"}]},{"given":"Tormod","family":"Volden","sequence":"additional","affiliation":[{"name":"CSEM SA, Untere Gr\u00fcndlistrasse 1, 6055 Alpnach, Switzerland"}]},{"given":"Michael","family":"Ningler","sequence":"additional","affiliation":[{"name":"LRE Medical, Hofer Strasse 5, 86720 Noerdlingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-2581","authenticated-orcid":false,"given":"Christos","family":"Kouloumentas","sequence":"additional","affiliation":[{"name":"Institute of Communication and Computer Systems (ICCS), National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}]},{"given":"Claudia","family":"Strehle","sequence":"additional","affiliation":[{"name":"LRE Medical, Hofer Strasse 5, 86720 Noerdlingen, Germany"}]},{"given":"Vincent","family":"Revol","sequence":"additional","affiliation":[{"name":"CSEM SA, Untere Gr\u00fcndlistrasse 1, 6055 Alpnach, Switzerland"}]},{"given":"Apostolos","family":"Klinakis","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation of the Academy of Athens, Soranou Ephessiou 4, 11527 Athens, Greece"}]},{"given":"Hercules","family":"Avramopoulos","sequence":"additional","affiliation":[{"name":"Institute of Communication and Computer Systems (ICCS), National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6341-4495","authenticated-orcid":false,"given":"Ioanna","family":"Zergioti","sequence":"additional","affiliation":[{"name":"Institute of Communication and Computer Systems (ICCS), National Technical University of Athens, Heroon Polytehneiou 9, 15780 Athens, Greece"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"ref_1","unstructured":"(2013, October 25). Use of \u2018-Omics\u2019 Technologies in the Development of Personalised Medicine. Available online: https:\/\/ec.europa.eu\/research\/health\/pdf\/2013-10_personalised_medicine_en.pdf."},{"key":"ref_2","unstructured":"(2013, October 30). Paving the Way for Personalized Medicine, FDA\u2019s Role in a New Era of Medical Product Development. Available online: https:\/\/www.fdanews.com\/ext\/resources\/files\/10\/10-28-13-Personalized-Medicine.pdf."},{"key":"ref_3","unstructured":"(2021, February 03). The Global Cancer Observatory (GCO). Available online: http:\/\/globocan.iarc.fr\/Default.aspx."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.cell.2006.11.001","article-title":"Cancer Metastasis: Building a Framework","volume":"127","author":"Gupta","year":"2006","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.biopha.2018.07.145","article-title":"Current trends and emerging diagnostic techniques for lung cancer","volume":"106","author":"Prabhakar","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.snb.2013.07.078","article-title":"Biomarkers and biosensors for the early diagnosis of lung cancer","volume":"188","author":"Altintas","year":"2013","journal-title":"Sens. Actuators B Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.bios.2016.08.028","article-title":"Biosensors for breast cancer diagnosis: A review of bioreceptors, biotransducers and signal amplification strategies","volume":"88","author":"Mittal","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bios.2016.12.014","article-title":"Recent advances in biosensor development for the detection of cancer biomarkers","volume":"91","author":"Jayanthi","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6546","DOI":"10.1021\/nn3023969","article-title":"Electrochemical immunosensors for detection of cancer protein biomarkers","volume":"6","author":"Chikkaveeraiah","year":"2012","journal-title":"ACS Nano"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.talanta.2006.09.029","article-title":"Optical sensors and biosensors based on sol-gel films","volume":"72","author":"Jeronimo","year":"2007","journal-title":"Talanta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-4939-6634-9_9","article-title":"Mass-Sensitive Biosensor Systems to Determine the Membrane Interaction of Analytes","volume":"1520","author":"Bendas","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.bios.2017.09.003","article-title":"Shifting paradigm of cancer diagnoses in clinically relevant samples based on miniaturized electrochemical nanobiosensors and microfluidic devices","volume":"100","author":"Mahato","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1002\/elan.201800193","article-title":"Electrochemical Biosensing in Cancer Diagnostics and Follow-up","volume":"30","author":"Freitas","year":"2018","journal-title":"Electroanalysis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.aca.2008.05.022","article-title":"Sensitive optical biosensors for unlabeled targets: A review","volume":"620","author":"Fan","year":"2008","journal-title":"Anal. Chim. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Heideman, R.G., Leinse, A., Geuzebroek, D.H., Schreuder, F., Falke, F., Zergioti, I., van der Meer, A., Schuetz-Trilling, A., Scheres, L., and Vestering-Stenger, R. (2020, January 3\u20136). Ultra-sensitive photonic integrated circuit-based biosensors for healthcare applications. Proceedings of the Integrated Optics: Devices, Materials, and Technologies XXIV, San Francisco, CA, USA.","DOI":"10.1117\/12.2551879"},{"key":"ref_16","first-page":"1000209","article-title":"Performance of Arrayed Microring Resonator Sensors with the TriPleX Platform","volume":"7","author":"Besselink","year":"2016","journal-title":"J. Biosens. Bioelectron."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1515\/aot-2015-0016","article-title":"TriPleX: A versatile dielectric photonic platform","volume":"4","author":"Heideman","year":"2015","journal-title":"Adv. Opt. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7611","DOI":"10.1364\/OE.24.007611","article-title":"New set of design rules for resonant refractive index sensors enabled by FFT based processing of the measurement data","volume":"24","author":"Gounaridis","year":"2016","journal-title":"Opt. Express"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7483","DOI":"10.1364\/OE.25.007483","article-title":"High performance refractive index sensor based on low Q-factor ring resonators and FFT processing of wavelength scanning data","volume":"25","author":"Gounaridis","year":"2017","journal-title":"Opt. Express"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1021\/la803094y","article-title":"Covalently Attached Organic Monolayers on SiC and SixN4 Surfaces: Formation Using UV Light at Room Temperature","volume":"25","author":"Rosso","year":"2009","journal-title":"Langmuir"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"025006","DOI":"10.1088\/2043-6262\/6\/2\/025006","article-title":"Chemical modification of silicon nitride microsieves for capture of MCF-7 circulating tumor cells of breast cancer","volume":"6","author":"To","year":"2015","journal-title":"Adv. Nat. Sci. Nanosci. Nanotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1021\/acs.langmuir.6b02860","article-title":"Direct Creation of Biopatterns via a Combination of Laser-Based Techniques and Click Chemistry","volume":"33","author":"Chatzipetrou","year":"2017","journal-title":"Langmuir"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1038\/s41598-017-01817-x","article-title":"Quantitative Detection of Weak D Antigen Variants in Blood Typing using SPR","volume":"7","author":"Then","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ab.2014.02.011","article-title":"Unconventional surface plasmon resonance signals reveal quantitative inhibition of transcriptional repressor EthR by synthetic ligands","volume":"452","author":"Crauste","year":"2014","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17169","DOI":"10.1039\/C6NR04897H","article-title":"Design of a novel plasmonic nanoconjugated analytical tool for ultrasensitive antigen quantification","volume":"8","author":"Fraire","year":"2016","journal-title":"Nanoscale"},{"key":"ref_26","unstructured":"Gounaridis, L., Groumas, P., Schreuder, E., Tsokos, C., Mylonas, E., Raptakis, A., Heideman, R., Avramopoulos, H., and Kouloumentas, C. (February, January 29). Design of ultra-compact multimode interference (MMI) couplers and high efficiency grating couplers in TriPleX platform as part of a photonic-based sensor. Proceedings of the Integrated Optics: Devices, Materials, and Technologies XXIII, San Francisco, CA, USA."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.snb.2014.11.098","article-title":"Design of grating couplers and MMI couplers on the TriPleX platform enabling ultra-compact photonic-based biosensors","volume":"209","author":"Gounaridis","year":"2015","journal-title":"Sens. Actuators B Chem."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/6\/2230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:39:32Z","timestamp":1760161172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/6\/2230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,23]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["s21062230"],"URL":"https:\/\/doi.org\/10.3390\/s21062230","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,23]]}}}