Introduction
Trace liquid analysis is crucial in fields such as biomedical diagnosis, environmental monitoring, and chemical process control. Traditional detection technologies often face bottlenecks including insufficient sensitivity, bulky equipment, and complex operations. Surface-Enhanced Raman Scattering (SERS) technology has emerged as a powerful tool for trace detection due to its molecular fingerprint identification capability. However, conventional SERS suffers from limitations such as low signal collection efficiency and intricate calibration procedures. The innovative integration of optical waveguide and SERS technologies, combined with cutting-edge approaches like artificial intelligence and femtosecond laser processing, has led to the development of ultra-sensitive, portable detection platforms. This integration enables a transformative shift from laboratory-based analysis to on-site real-time monitoring, revolutionizing trace liquid detection.
Recently, a research team led by Associate Researcher Danheng Gao from Haoran Meng's group at the State Key Laboratory of Advanced Manufacturing for Optical Systems, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), in collaboration with Professor Xinghua Yang from Harbin Engineering University and other teams, published a review article titled "Emerging frontiers in SERS-integrated optical waveguides: advancing portable and ultra-sensitive detection for trace liquid analysis" in Light: Science & Applications. This study systematically reviews the development trajectory of SERS-integrated optical waveguide technology, delves into key research directions including waveguide structure design, sensing interface optimization, and integration of emerging technologies, and focuses on analyzing two major technical pathways: remote sensing probes and microfluidic sensing platforms. It provides comprehensive references for the development of next-generation ultra-sensitive detection technologies. Danheng Gao from CIOMP is the first author of the paper, while Meng Luo and Haoran Meng are the corresponding authors.
1. SERS-Optical Waveguide Integration: Breaking the Bottlenecks of Traditional Detection
Conventional SERS technology relies on the Localized Surface Plasmon Resonance (LSPR) effect of noble metal nanostructures to enhance Raman signals. However, its detection performance is limited by issues such as mismatched excitation and collection efficiency, and complex sample handling. Optical waveguides, with their advantages of mechanical flexibility, electromagnetic interference resistance, and strong light field confinement capabilities, form a perfect complement to SERS technology. Through waveguide-mediated light-matter interactions, they achieve dual improvements: efficient excitation of analytes and enhanced collection of scattered signals.
Core Integration Mechanisms
The integration of optical waveguides and SERS is primarily accomplished through two core pathways:
Remote Sensing Probes: Functional modification of SERS substrates (including silver/gold nanoparticles, nanocavity arrays, and other structures) on the end faces of optical fibers. Leveraging the long-distance transmission capability of optical fibers, in-situ and non-destructive detection is enabled, making it suitable for scenarios such as in-vivo and in-vitro biological sample analysis.
Microfluidic Sensing Platforms: Utilizing the internal porous characteristics of microstructured optical waveguides such as Photonic Crystal Fibers (PCFs) and Hollow-Core Anti-Resonant Fibers (HcARFs) to construct SERS detection systems integrated with microchannels, enabling continuous-flow analysis of samples at the nanoliter or even attoliter scale.
Key Performance Improvements
As shown in Fig. 2, this integrated technology has significantly overcome the limitations of traditional detection:
Through evanescent field coupling, the interaction between light and samples is enhanced, resulting in a 1-3 order of magnitude improvement in detection sensitivity compared to conventional SERS.
The optical path calibration process is simplified, and the device size is significantly reduced, laying the foundation for portable detection.
Sample consumption is reduced to below the microliter level, making it particularly suitable for the analysis of rare biological samples. For instance, SERS sensors based on Suspended-Core Fibers (SCFs) achieve a detection limit of 10-14 mol/L for Rhodamine 6G (R6G) with an enhancement factor as high as 1.3×109
2. Technical Innovation Pathways: From Structural Design to Performance Optimization
The development of SERS-integrated optical waveguide technology has always centered on structural innovation and performance improvement, forming a multi-dimensional and multi-level technical system.
Iterative Upgrades of Remote Sensing Probes
Early approaches involving functional modification of SERS substrates on optical fiber end faces enabled remote detection but suffered from issues such as small sensing areas and insufficient signal stability. Research teams have continuously made breakthroughs through structural optimization:
Tilted End Faces Combined with Nanostructures: Processing the optical fiber end face into a 40° tilt angle and modifying it with Ag/Al2O3 nanostructures, enabling remote detection up to 95 meters and significantly improving plasmonic coupling efficiency.
Special Morphology Optical Fiber Design: Tapered optical fiber probes achieve localized detection by reducing the end face size, with a spatial resolution reaching the sub-micron level; D-shaped fibers expose the fiber core through side polishing, expanding the SERS-active area by 1.6×103 times and enhancing signals by three orders of magnitude.
Composite Substrate Construction: Composite structures of gold nanocavity arrays and silver nanoparticles achieve a detection limit of 0.1 pg for acetaminophen through the synergistic effect of multiple reflection light trapping and LSPR, meeting the requirements of pharmaceutical analysis.
Technological Breakthroughs in Microfluidic Optical Waveguide Platforms
The emergence of microstructured optical waveguides has driven the development of SERS detection towards microfluidic integration, enabling automated analysis of trace samples:
Photonic Crystal Fibers (PCFs): By modifying SERS substrates on the inner walls of hollow fiber cores and utilizing the bandgap effect to confine the light field, the interaction length between light and matter is extended, achieving a detection limit of 10⁻¹⁰ mol/L for R6G.
Hollow-Core Anti-Resonant Fibers (HcARFs): Confining the light field in air channels to reduce background interference from fiber materials, and combining modification with Ag/ZnO nanocomposites to achieve single-molecule detection of exosomes with an enhancement factor exceeding 109.
Suspended-Core Fibers (SCFs): The fiber core is suspended in air holes to form a strong evanescent field. Through the design of microchannels, sufficient contact between samples and SERS substrates is achieved. It has been successfully applied to the ultra-sensitive detection of biomolecules such as cerebrospinal fluid glucose and DNA adenine, with a detection time of only 25-30 seconds.
3. Empowerment by Emerging Technologies: Advancing Towards Practical Detection Heights
To further enhance detection performance and promote technology implementation, research teams have deeply integrated SERS-optical waveguide integration technology with emerging methods such as femtosecond laser processing, cavity enhancement technology, and artificial intelligence, addressing challenges in structure fabrication and signal analysis faced by traditional methods.
Breakthroughs in Advanced Fabrication Technologies
Femtosecond Laser Direct Writing: Enabling high-precision, large-area fabrication of SERS substrates. By constructing superhydrophobic/hydrophilic composite platforms through femtosecond laser-induced periodic surface structures (LIPSS) combined with silver nanoparticle deposition, the detection limit for crystal violet is reduced to 1.22×10-15 mol/L.
Multi-Material Composite Modification: Combining two-dimensional materials such as graphene and MXenes with noble metal nanoparticles not only inhibits nanoparticle aggregation but also enhances Raman signals through the charge transfer effect, improving detection stability.
Innovations in Signal Enhancement and Analysis
Cavity Enhancement Technology: Achieving multiple reflections of the light field through structures such as photonic crystal microcavities and Fabry-Pérot (FP) cavities, further enhancing the LSPR effect and increasing the signal enhancement factor by an additional order of magnitude.
Artificial Intelligence-Assisted Analysis: As shown in Fig. 3, utilizing algorithms such as Convolutional Neural Networks (CNNs) and Principal Component Analysis (PCA) to process complex Raman spectra, effectively eliminating background interference and enabling accurate identification of multi-component mixed samples. For example, SERS systems based on machine learning have successfully achieved rapid detection of the SARS-CoV-2 virus with an accuracy exceeding 98%.
4. Application Scenarios and Future Prospects
SERS-integrated optical waveguide technology has demonstrated great application potential in multiple fields:
In the biomedical field, it enables ultra-sensitive detection of tumor markers, neurotransmitters, and nucleic acid bases, providing support for early disease diagnosis.
In environmental monitoring, it can rapidly detect heavy metal ions, pesticide residues, and other pollutants in water bodies with a detection limit reaching the nanomolar level.
In food safety, it allows on-site rapid screening of pathogenic bacteria and additives.
Despite significant progress in research and applications, several challenges remain: high manufacturing costs of special-structured optical waveguides, insufficient detection specificity for complex matrix samples, and the need for further optimization of long-term stability and repeatability. Future research will focus on three key directions:
Development of low-cost, scalable fabrication technologies for SERS substrates and optical waveguide integration.
Construction of multi-modal integrated detection systems, combining technologies such as fluorescence and Localized Surface Plasmon Resonance (LSPR) to improve specificity.
Deep integration of artificial intelligence with detection systems to achieve full-process automation from sample preprocessing to result analysis.
Development of miniaturized, low-power portable devices to promote the implementation of the technology in scenarios such as clinical point-of-care testing and on-site environmental monitoring. END