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Cancer Manag Res. 2019 Jan 31;11:1115-1124. doi: 10.2147/CMAR.S185375. eCollection 2019.

SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer.

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Laboratory of Bio-optical Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (ASTAR), Singapore,
Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Mathematics, Brunel University London, Uxbridge, UK.



To evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting.


SERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections.


Hp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity.


With a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intra-operative EOC diagnostic test.


epithelial ovarian cancer; haptoglobin; ovarian cyst fluid; point-of-care diagnostics; surface-enhanced Raman spectroscopy

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