Surface-enhanced Raman spectroscopy (SERS) is an optical sensing technology based on local surface plasmon resonance, which greatly enhances the Raman signal of molecules adsorbed or very close to the surface of rough nano-metals, even achieving single-molecule detection. The traditional SERS substrate is created by depositing precious metal nanoparticles (Ag, Au, Cu, etc.) on rigid substrates such as slides and silicon wafers. The preparation process of such substrates is relatively mature, offering good stability and sensitivity, and is widely used in molecular recognition, quantitative analysis, and other fields. However, complicated experimental pretreatment steps, high cost, high operational requirements, and fixed detection platform shapes limit the application range of SERS technology, making it unsuitable for sampling and detection of objects with complex shapes and irregular surfaces. To improve the flexibility and portability of detection, reduce costs and operational requirements, and broaden the application range of SERS technology, researchers have focused on developing new SERS substrates, with flexible SERS substrates attracting significant attention. Flexible substrates possess good flexibility and plasticity, and can be cut to any desired shape and size to accommodate various complex shapes and irregular surfaces, offering great advantages in non-destructive and in-situ detection. This review introduces the research progress in SERS technology based on flexible substrates in recent years. Firstly, different methods of constructing flexible SERS substrates using various flexible materials, including cellulose flexible substrates, polymer flexible substrates and other flexible materials, are discussed, highlighting the advantages and challenges of each. Additionally, the latest applications of flexible SERS substrates in biomedicine, food safety, and environmental monitoring are summarized.

First, based on the introduction of common materials for constructing flexible SERS substrates, including cellulose, polymer flexible films, and materials from natural organisms, this review outlines different methods for constructing SERS substrates under these materials and discusses their respective advantages and challenges. The natural 3D hotspot structure of cellulose makes it a reliable material for the green synthesis of nanoparticles and the manufacture of flexible SERS substrates. Cellulose paper-based SERS substrates have been widely studied due to their renewability and low cost (Fig. 2), with some unique preparation methods being highlighted (Fig. 3). Polymer films are extensively used in the SERS field due to their flexibility, transparency, and biocompatibility (Fig. 5). Additionally, various biological materials are increasingly attracting researchers’ attention due to their inherent properties or natural structures (Fig. 6). This study also reviews and summarizes recent applications of flexible SERS substrates in biomedicine, food safety, and environmental monitoring methods. Furthermore, the optimization strategies and challenges in various application scenarios based on flexible SERS substrates are summarized and anticipated.

Although flexible SERS substrates have been widely studied, challenges remain in their practical application. Material selection is critical, as uniformity and reproducibility of the SERS spectrum can be affected by varying pore sizes, chemical compositions, uneven distribution of reducing agents, and different aggregation states of plasma nanoparticles at different locations. The preparation process may involve the use of volatile organic solvents that are not environmentally friendly and can release harmful substances, leading to negative environmental effects. Differences between various organisms can impact experimental reproducibility. Adjusting the composition, morphology, and structure of nanoparticles, and introducing surface modification or pretreatment steps can improve substrate performance. Currently, most high-performance SERS substrates rely on precious metal nanostructures, and their high cost hinders mass production. Therefore, it is essential to explore more environmentally friendly, green, and high-performance SERS substrates, including the preparation of renewable substrates and the development of substrates with self-cleaning capabilities. In practical applications, the complex and diverse composition of objects presents a challenge for the multiplexed detection capability of flexible SERS substrates. Thus, combining SERS with other technologies such as molecular imprinted polymers (MIPs), immune recognition, microfluidic technology, and machine learning can help construct a SERS sensing platform suitable for multi-target detection. Furthermore, with the miniaturization of Raman spectrometers, SERS technology is expected to reduce dependence on large Raman spectroscopy instruments. Combined with flexible SERS substrates, SERS technology can potentially offer a new and rapid optical detection method for many special scenarios, including field exploration, emergency incident handling, criminal investigation, entry-exit border inspection, and clinical bedside detection.