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Nanoscale irregularities in such substrates\/NPs could lead to SERS sensors with poor reproducibility and repeatability. Herein, we demonstrate a suspended core photonic crystal fiber (PCF) based SERS sensor with extremely high reproducibility and repeatability in measurement with a relative SD of only 1.5% and 4.6%, respectively, which makes it more reliable than any existing SERS sensor platforms. In addition, our platform could improve the detection sensitivity owing to the increased interaction area between the guided light and the analyte, which is incorporated into the holes that runs along the length of the PCF. Numerical calculation established the significance of the interplay between light coupling efficiency and evanescent field distribution, which could eventually determine the sensitivity and reliability of the developed SERS active\u2010PCF sensor. As a proof of concept, using this sensor, we demonstrated the detection of haptoglobin, a biomarker for ovarian cancer, contained within the ovarian cyst fluid, which facilitated in differentiating the stages of cancer. We envision that with necessary refinements, this platform could potentially be translated as a next\u2010generation highly sensitive SERS\u2010active opto\u2010fluidic biopsy needle for the detection of biomarkers in body fluids.<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio201960120-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.201960120","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T02:00:25Z","timestamp":1575856825000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Development of highly reliable SERS\u2010active photonic crystal fiber probe and its application in the detection of ovarian cancer biomarker in cyst fluid"],"prefix":"10.1002","volume":"13","author":[{"given":"Flavien","family":"Beffara","sequence":"first","affiliation":[{"name":"Lab of Bio\u2010Optical Imaging, Singapore Bioimaging Consortium (SBIC) Agency for Science Technology and Research (A*STAR)  Singapore Singapore"},{"name":"XLIM Research Institute UMR 7252 CNRS\/Limoges University  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayakumar","family":"Perumal","sequence":"additional","affiliation":[{"name":"Lab of Bio\u2010Optical Imaging, Singapore Bioimaging Consortium (SBIC) Agency for Science Technology and Research (A*STAR)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniza","family":"Puteri Mahyuddin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Yong Loo Lin School of Medicine, National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Choolani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Yong Loo Lin School of Medicine, National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saif A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemical and Bimolecular Engineering National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Auguste","sequence":"additional","affiliation":[{"name":"XLIM Research Institute UMR 7252 CNRS\/Limoges University  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Vedraine","sequence":"additional","affiliation":[{"name":"XLIM Research Institute UMR 7252 CNRS\/Limoges University  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Humbert","sequence":"additional","affiliation":[{"name":"XLIM Research Institute UMR 7252 CNRS\/Limoges University  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U. 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