Quantitative Detection of CD44-Expressing Cancer Cells Using Label-Free Optical Fiber Biosensors with Quasi-Random Interferometry

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Authors

Marzhan Nurlankyzy

Laboratory of Biosensors and Bioinstruments, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan.

Kanagat Kantoreyeva

School of Engineering and Digital Sciences, Nazarbayev University, Astana, Kazakhstan

Aida Zhakypbekova

School of Engineering and Digital Sciences, Nazarbayev University, Astana, Kazakhstan

Zhannat Ashikbayeva

Laboratory of Biosensors and Bioinstruments, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, School of Sciences and Humanities, Astana, Kazakhstan

Damira Kanayeva

School of Sciences and Humanities, Astana, Nazarbayev University, Astana, Kazakhstan

Carlos Marques

CICECO - Aveiro Institute of Materials, Physics Department, University of Aveiro, Department of Physics, Faculty of Electrical Engineering and Computer Science, VSB—Technical University of Ostrava, Ostrava, Kazakhstan

Santosh Kumar

Centre of Excellence for Nanotechnology, Department of Electronics and Communication Engineering, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India.

Milan Kovacevic

University of Kragujevac, Faculty of Science, Kragujevac, Serbia

Wilfried Blanc

Université Côte d’Azur, CNRS, INPHYNI, Nice, France

Constantinos Valagiannopoulos

School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece

Aliya Bekmurzayeva

Laboratory of Biosensors and Bioinstruments, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan

Daniele Tosi

Laboratory of Biosensors and Bioinstruments, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
School of Engineering and Digital Sciences, Nazarbayev University, Astana, Kazakhstan

Abstract

Background: Circulating tumor cells (CTCs), key biomarkers in cancer progression and metastasis, hold significant value for early cancer detection as predictive and prognostic indicators. However, detecting and quantifying whole cells remains challenging due to their rarity, with most prior research focusing on protein biomarker detection instead. In this study, we present a quasi- random interferometer-based optical fiber biosensor designed for real-time, label-free, and quantitative detection of cancer cells expressing CD44. The sensor is low-cost, easy to fabricate, and functions as a weak interferometer capable of differentiating cancer cells from normal cells. Its detection mechanism relies on local refractive index variations near the sensor tip, correlated with CD44 expression in a concentration-dependent manner.

Materials and methods: Sensor fabrication and calibration, biofunctionalization of sensors, cell culture, imaging and flow cytometry, and data analysis.

Results: The sensor demonstrated a limit of detection (LoD) of 48.8 cells/mL and a sensitivity of dB/10×.

Conclusion: This approach lays the groundwork for developing microfluidic systems and multiplexed CTC detection, representing an important step toward clinical translation.

Acknowledgements:

This research has been funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan (Grant No AP22783767), and by Nazarbayev University grants, code: 20122022FD4134 (Project M2O-DISK). This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020), UIDP/50011/2020    (DOI    10.54499/UIDP/50011/2020)    &    LA/P/0006/2020    (DOI

10.54499/LA/P/0006/2020) financed by national funds through the FCT/MCTES (PIDDAC). The research was co-funded by the financial support of the European Union under the REFRESH – Research Excellence For REgion Sustainability and High-tech Industries project number CZ.10.03.01/00/22003/0000048 via the Operational Programme Just Transition. This work was also supported by the Ministry of Education, Youth, and Sports of the Czech Republic conducted by the VSB-Technical University of Ostrava, under grant no. SP2025/039.

Keywords: Optical fiber biosensor, cancer cells detection, breast cancer, cell biosensing, quasi- random interferometer.

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