A new publication from Opto-Electronic Advances; DOI 10.29026/oea.2024.240105, discusses a high-resolution tumor marker detection based on microwave photonics demodulated dual wavelength fiber laser sensing system for the early screening of cancer.

The detection of trace cancer markers in bodily fluids, such as blood and serum, is crucial for early screening of cancer diseases, guidance of treatment and prognosis assessment. The scarcity of tumor markers in test samples and the complexity of the test environment pose significant challenges to optical sensor performance, particularly in terms of sensitivity, demodulation resolution, and specificity. Optical fiber sensors, which utilize optical fibers as the carrier and integrate optical detection and optical signal transmission, is a research hotspot. Thanks to continuous technological innovations and optimizations by numerous researchers, the sensitivity of sensors based on various precision designs has seen substantial improvements. For instance, the sensitivity of optical fiber sensors can be greatly enhanced by self-assembling and attaching two-dimensional materials, metallic micro- and nanoparticles, and deposited films to their surfaces, achieving local electromagnetic field amplification. The antigen sandwich method, rooted in immunoassay, offers an effective strategy for amplifying signals generated by biomolecular binding events. However, in the realm of optical fiber biosensors, a balance must still be struck between the responsiveness and stability of the sensing signal. Many structural designs can boost sensitivity but may compromise the stability and repeatability of the sensor, which is a tradeoff in practical applications. Compared to the interference spectrum of traditional fiber sensors, the narrow linewidth and high signal-to-noise ratio (SNR) of fiber laser signals pave a new way for enhancing the spectral resolution of optical fiber sensing technology. Yet, traditional optical fiber sensors typically rely on wavelength monitoring, which is accomplished using an optical spectral analyzer (OSA) with an optimal wavelength resolution of 0.02 nm. This implies that when OSA is used to analyze spectral wavelength shifts, which reflect the sensing signal, only changes of GHz and larger frequencies can be resolved, thereby limiting the detection resolution of optical fiber sensors. To distinguish the weak signals produced by trace tumor markers, ultra-high-resolution demodulation methods are imperative for improving the detection performance of optical fiber biosensors.

Recently, Professor Shao Liyang's research group from Southern University of Science and Technology proposed a dual-wavelength fiber laser biosensor system leveraging microwave photonics demodulation technology for the specific detection of tumor markers in serum. Firstly, a micro-lasso-shaped optical fiber sensor was designed and connected with fiber Bragg grating in parallel to construct a dual-wavelength laser output system. A microwave photonics demodulation optical path, based on time delays induced by optical dispersion, was constructed to demodulate the dual-wavelength laser sensing signals. During experimental detection, three distinct demodulation schemes were implemented simultaneously: analysis of laser spectral wavelength changes, analysis of Free Spectral Range (FSR) reduction in microwave photonics demodulated radiofrequency (RF) spectra, and analysis of maximum Notch frequency reduction in RF spectra. A detailed comparison of their detection performances was conducted. The refractive index (RI) sensitivity of the laser sensing system, based on laser wavelength demodulation, was found to be 1083 nm/RIU. Meanwhile, the RI sensitivities achieved through FSR reduction analysis and maximum Notch frequency reduction analysis, utilizing microwave photonics demodulation technology, reached -535.56 GHz/RIU and -1902 GHz/RIU, respectively.

The corresponding ideal detection resolution improved from 1.9×10^-5 RIU to 1.87×10^-7 RIU and 5.26×10^-8 RIU, respectively, with a performance improvement of 2 to 3 orders of magnitude. In comparison with other recently published optical fiber sensing technologies—including those based on spectral wavelength shifts, light intensity changes, speckle analysis, and microwave photonics demodulation—the sensor system proposed in this study exhibited higher sensitivity, higher resolution, and superior real detection accuracy in RI detection. To validate the biosensing capabilities of the sensor, CEACAM5 was selected as the target for detection. Test results in PBS buffer revealed that the Limit of Detection (LOD) of the sensor system, based on microwave photonic demodulation, was as low as 0.076 ng/mL—representing an order of magnitude improvement over the detection performance of traditional laser spectral wavelength demodulation schemes. Furthermore, additional testing on human serum samples confirmed the practical application performance of the sensor system. The three experimental schemes effectively discriminated between marker content differences in various human serum samples, aligning with the clinical values provided by the hospital. In contrast to the traditional spectral wavelength demodulation method, the microwave photonics demodulation technology, based on dispersion-induced delays, significantly enhanced detection accuracy and resolution, lowered the detection limit, and offered new possibilities for a broader range of biological detection scenarios.

Keywords: optical fiber sensor / optical fiber laser / microwave photonics demodulation / high-resolution detection / tumor marker detection
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Shao Liyang, professor/doctoral supervisor, European foreign academician, National special young expert, Deputy Dean of the School of Innovation and Entrepreneurship of Southern University of Science and Technology, dual researcher of Pengcheng Laboratory/Southern Ocean Laboratory, director of the Research Center for the Integrated Intelligent Network of Heaven, Earth and Sea, Executive director of Guangdong Integrated Photoelectric Sensing Laboratory, Major project of the Ministry of Science and Technology/Foundation Committee/National Award review expert. He received his PhD in Optical Engineering from Zhejiang University in 2008. After graduation, he has engaged in scientific research work in well-known universities such as Carleton University in Canada, University of Sydney in Australia, Hong Kong Polytechnic University, and Nanyang Technological University in Singapore. His research interests include distributed optical fiber sensing technology and engineering applications, key technologies and applications of integrated intelligent network between heaven, earth and sea. He has published more than 200 academic papers in major international journals and conferences, including 8 articles published in Nat.Comm. \Light Sci.Appl. \Opto-Electronic Advances \Laser Photon. Rev. \ Adv.Electron.Mater. \Nanoscale \Biosen. and Bioelectron. these top journals, with a total of 7,479 citations by Google Scholar, H-factor 47. He was invited to write 4 review articles, gave 2 keynote reports at important international conferences such as IEEE ICCT, CLEO-PR, APOS, and more than 20 invited reports. He served as TPC Chair/ organizing committee member of ACP2022, OGC2020/21/22 and CLEO-PR 2018/2020 International conferences for more than 20 times; He has more than 10 authorized invention patents. He has won the Australian "Advancing Scholar Award", the National Special Young Expert, the "Zhan Tianyou Railway Science and Technology Award Youth Award", the "Shenzhen Industrial Development and Innovation Talent Award", the China Industry-University-Research Cooperation Promotion Award (individual), the second prize of the Chinese Optical Engineering Society Technology Invention Award and other honors, and has been selected as the "Top 2% of the World's Top Scientists" by Stanford University for four consecutive years. Includes the "Lifetime Science Impact List" and the "Annual Science Impact List." In recent years, he has presided over more than 10 projects such as the Ministry of Science and Technology and the National Natural Science Foundation.

Xiao Dongrui (second corresponding author) completed his PhD in 2022 through a joint training program between Harbin Institute of Technology (Harbin, China) and Southern University of Science and Technology (Shenzhen, China), receiving his degree in engineering from Harbin Institute of Technology. His research focuses on microwave photonics and optical fiber sensing technology, specifically engaging in cross-disciplinary theoretical and applied research involving microwave photonic filters, optoelectronic oscillators, fiber lasers, and optical fiber sensor technology. He currently holds the position of associate professor at Hunan Institute of Technology.

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Hu J, Lin WH, Shao LY et al. High-resolution tumor marker detection based on microwave photonics demodulated dual wavelength fiber laser sensor. Opto-Electron Adv 7, 240105 (2024). doi: 10.29026/oea.2024.240105