Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection
The accuracy and efficacy of medical treatment would be greatly improved by the continuous and real-time monitoring of protein biomarkers. Identification of cancer biomarkers in patients with solid malignant tumors is receiving increasing attention. Existing techniques for detecting cancer proteins,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Sensors |
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| Online Access: | https://www.mdpi.com/1424-8220/24/6/1991 |
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| author | Zhuldyz Myrkhiyeva Kanagat Kantoreyeva Aliya Bekmurzayeva Anthony W. Gomez Zhannat Ashikbayeva Meruyert Tilegen Tri T. Pham Daniele Tosi |
| author_facet | Zhuldyz Myrkhiyeva Kanagat Kantoreyeva Aliya Bekmurzayeva Anthony W. Gomez Zhannat Ashikbayeva Meruyert Tilegen Tri T. Pham Daniele Tosi |
| author_sort | Zhuldyz Myrkhiyeva |
| collection | DOAJ |
| description | The accuracy and efficacy of medical treatment would be greatly improved by the continuous and real-time monitoring of protein biomarkers. Identification of cancer biomarkers in patients with solid malignant tumors is receiving increasing attention. Existing techniques for detecting cancer proteins, such as the enzyme-linked immunosorbent assay, require a lot of work, are not multiplexed, and only allow for single-time point observations. In order to get one step closer to clinical usage, a dynamic platform for biosensing the cancer biomarker CD44 using a single-mode optical fiber-based ball resonator biosensor was designed, constructed and evaluated in this work. The main novelty of the work is an in-depth study of the capability of an in-house fabricated optical fiber biosensor for in situ detection of a cancer biomarker (CD44 protein) by conducting several types of experiments. The main results of the work are as follows: (1) Calibration of the fabricated fiber-optic ball resonator sensors in both static and dynamic conditions showed similar sensitivity to the refractive index change demonstrating its usefulness as a biosensing platform for dynamic measurements; (2) The fabricated sensors were shown to be insensitive to pressure changes further confirming their utility as an in situ sensor; (3) The sensor’s packaging and placement were optimized to create a better environment for the fabricated ball resonator’s performance in blood-mimicking environment; (4) Incubating increasing protein concentrations with antibody-functionalized sensor resulted in nearly instantaneous signal change indicating a femtomolar detection limit in a dynamic range from 7.1 aM to 16.7 nM; (5) The consistency of the obtained signal change was confirmed by repeatability studies; (6) Specificity experiments conducted under dynamic conditions demonstrated that the biosensors are highly selective to the targeted protein; (7) Surface morphology studies by AFM measurements further confirm the biosensor’s exceptional sensitivity by revealing a considerable shift in height but no change in surface roughness after detection. The biosensor’s ability to analyze clinically relevant proteins in real time with high sensitivity offers an advancement in the detection and monitoring of malignant tumors, hence improving patient diagnosis and health status surveillance. |
| first_indexed | 2024-04-24T17:49:26Z |
| format | Article |
| id | doaj.art-6afeb37cbfee466ca988cd7f2672a6dc |
| institution | Directory Open Access Journal |
| issn | 1424-8220 |
| language | English |
| last_indexed | 2024-04-24T17:49:26Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Sensors |
| spelling | doaj.art-6afeb37cbfee466ca988cd7f2672a6dc2024-03-27T14:04:19ZengMDPI AGSensors1424-82202024-03-01246199110.3390/s24061991Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein DetectionZhuldyz Myrkhiyeva0Kanagat Kantoreyeva1Aliya Bekmurzayeva2Anthony W. Gomez3Zhannat Ashikbayeva4Meruyert Tilegen5Tri T. Pham6Daniele Tosi7Laboratory of Biosensors and Bioinstruments, National Laboratory Astana, Nazarbayev University, 010000 Astana, KazakhstanDepartment of Electrical and Computer Engineering, School of Engineering and Digital Sciences, Nazarbayev University, 010000 Astana, KazakhstanLaboratory of Biosensors and Bioinstruments, National Laboratory Astana, Nazarbayev University, 010000 Astana, KazakhstanLaboratory of Biosensors and Bioinstruments, National Laboratory Astana, Nazarbayev University, 010000 Astana, KazakhstanLaboratory of Biosensors and Bioinstruments, National Laboratory Astana, Nazarbayev University, 010000 Astana, KazakhstanDepartment of Biology, School of Sciences and Humanities, Nazarbayev University, 010000 Astana, KazakhstanDepartment of Biology, School of Sciences and Humanities, Nazarbayev University, 010000 Astana, KazakhstanLaboratory of Biosensors and Bioinstruments, National Laboratory Astana, Nazarbayev University, 010000 Astana, KazakhstanThe accuracy and efficacy of medical treatment would be greatly improved by the continuous and real-time monitoring of protein biomarkers. Identification of cancer biomarkers in patients with solid malignant tumors is receiving increasing attention. Existing techniques for detecting cancer proteins, such as the enzyme-linked immunosorbent assay, require a lot of work, are not multiplexed, and only allow for single-time point observations. In order to get one step closer to clinical usage, a dynamic platform for biosensing the cancer biomarker CD44 using a single-mode optical fiber-based ball resonator biosensor was designed, constructed and evaluated in this work. The main novelty of the work is an in-depth study of the capability of an in-house fabricated optical fiber biosensor for in situ detection of a cancer biomarker (CD44 protein) by conducting several types of experiments. The main results of the work are as follows: (1) Calibration of the fabricated fiber-optic ball resonator sensors in both static and dynamic conditions showed similar sensitivity to the refractive index change demonstrating its usefulness as a biosensing platform for dynamic measurements; (2) The fabricated sensors were shown to be insensitive to pressure changes further confirming their utility as an in situ sensor; (3) The sensor’s packaging and placement were optimized to create a better environment for the fabricated ball resonator’s performance in blood-mimicking environment; (4) Incubating increasing protein concentrations with antibody-functionalized sensor resulted in nearly instantaneous signal change indicating a femtomolar detection limit in a dynamic range from 7.1 aM to 16.7 nM; (5) The consistency of the obtained signal change was confirmed by repeatability studies; (6) Specificity experiments conducted under dynamic conditions demonstrated that the biosensors are highly selective to the targeted protein; (7) Surface morphology studies by AFM measurements further confirm the biosensor’s exceptional sensitivity by revealing a considerable shift in height but no change in surface roughness after detection. The biosensor’s ability to analyze clinically relevant proteins in real time with high sensitivity offers an advancement in the detection and monitoring of malignant tumors, hence improving patient diagnosis and health status surveillance.https://www.mdpi.com/1424-8220/24/6/1991dynamic measurementin vitro detection optical fiber biosensorball resonatorCD44cancer biomarker |
| spellingShingle | Zhuldyz Myrkhiyeva Kanagat Kantoreyeva Aliya Bekmurzayeva Anthony W. Gomez Zhannat Ashikbayeva Meruyert Tilegen Tri T. Pham Daniele Tosi Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection Sensors dynamic measurement in vitro detection optical fiber biosensor ball resonator CD44 cancer biomarker |
| title | Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection |
| title_full | Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection |
| title_fullStr | Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection |
| title_full_unstemmed | Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection |
| title_short | Dynamic Measurement of a Cancer Biomarker: Towards In Situ Application of a Fiber-Optic Ball Resonator Biosensor in CD44 Protein Detection |
| title_sort | dynamic measurement of a cancer biomarker towards in situ application of a fiber optic ball resonator biosensor in cd44 protein detection |
| topic | dynamic measurement in vitro detection optical fiber biosensor ball resonator CD44 cancer biomarker |
| url | https://www.mdpi.com/1424-8220/24/6/1991 |
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