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
