Microwave photonics demodulated dual wavelength fibre laser sensing system assists in high-resolution tumour marker detection for early cancer screening

An article published in Opto-Electronic Advances discusses a method of high-resolution tumour marker detection based on microwave photonics, demodulated dual wavelength, fibre laser sensing system for the early screening of cancer.

The detection of trace cancer markers in bodily fluids ─ such as blood and serum ─ is important for effective deployment of screening programmes early in oncology diagnosis and any consequent guidance on treatment. The small quantities of tumour markers that are available in test samples, and the complexity of the test environment, pose significant challenges to optical sensor performance.

Optical fibre sensors, which use optical fibres as the carrier and integrate optical detection and optical signal transmission, is a research hotspot.

The sensitivity of sensors has seen substantial improvements following numerous researchers building on continuous technological innovation. For example, optical fibre sensor sensitivity is greatly enhanced by 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, with optical fibre biosensors, a balance must 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 trade-off in practical applications. Compared to the interference spectrum of traditional fibre sensors, the narrow linewidth and high signal-to-noise ratio of fibre laser signals offer opportunities to enhance the spectral resolution of optical fibre sensing technology.

Yet, traditional optical fibre sensors typically rely on wavelength monitoring, which is accomplished using an optical spectral analyser (OSA) with an optimal wavelength resolution of 0.02 nm. This implies that when OSA is used to analyse spectral wavelength shifts ─ which reflect the sensing signal ─ only changes of GHz or larger frequencies can be resolved. This therefore limits the detection resolution of optical fibre sensors. To distinguish the weak signals produced by trace tumour markers, ultra-high-resolution demodulation methods are imperative for improving the detection performance of optical fibre biosensors.

Professor Shao Liyang's research group from Southern University of Science and Technology, Shenzhen, China has proposed a dual-wavelength fibre laser biosensor system leveraging microwave photonics demodulation technology for the specific detection of tumour markers in serum. Firstly, a micro-lasso-shaped optical fibre sensor was designed and connected with fibre 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.
• 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, utilising 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 two to three orders of magnitude. In comparison with other recently published optical fibre 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 phosphate-buffered saline revealed that the limit of detection 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. 

For further reading please visit: 10.29026/oea.2024.240105