Local Electromagnetic Field Enhancement Research Articles

Multiple Fano resonances in all-dielectric porous array structures

High Q metasurfaces play an important role in fields such as high-sensitivity sensing and nonlinear optics due to their strong localized electromagnetic field enhancement. Although ultra-high Q resonance has been developed in the field of optics, it is still a challenging task due to the loss of dielectric materials, design and fabrication of nanostructures. In this paper, we have designed an all-dielectric symmetric perforated array structure that supports multiple Fano resonances within the 0–1 THz range and realizes the anapole mode through this array perforation structure. By calculating the phase difference between different modes at the resonance frequencies, we explain the mechanism of the formation of resonance-coupled BIC. The Q-factors of the three modes have been calculated, where the highest Q-value can be up to 2703, it is excited by the MQ. Then, we analyzed the sensing performance and the highest sensitivity can reach 27,000 nm/RIU. Since the metasurface always maintains c_4v symmetry and mirror symmetry, all three resonances are polarization independent. The proposed metasurfaces can be applied to light-matter interactions, enhanced nonlinear response, and sensing.

Super-Resolution Surface-Enhanced Raman Scattering: Perspectives on the Past, Present, and Future.

Super-resolution surface-enhanced Raman scattering (SERS) allows researchers to overcome the resolution limit of far field optical microscopy and peer into electromagnetic hot spots with nanoscale resolution. By localizing the signal from single (or few) molecules on the surface of plasmonic nanoparticle aggregates, relationships between the spatial origin of the SERS signal, local electromagnetic field enhancements, and SERS intensity can be determined. This Perspective describes the successes and challenges of super-resolution SERS, from the earliest mapping of single-molecule SERS hot spots to the current state-of-the-art, while highlighting open questions and future opportunities to advance the field. Comparisons with fluorescence-based super-resolution imaging are discussed to help frame the unique challenges associated with performing SERS in the super-resolution regime.

Shaping sub-10 nm metallic nanogaps by laser shock-induced extreme plasticity

The nanoscale metallic gaps generate the unique local electromagnetic field enhancement effect due to the strong electromagnetic coupling between closely spaced nanostructures. Besides the conventional material deposition or removal strategy, laser shock reshaping (LSR), based on the ultrahigh-strain-rate deformation of the nanometals, provides a viable process for ultrafine-gap fabrication. However, the extreme deformation behavior of nanometals during the high-speed forming process, which significantly determines the forming precision and quality, is largely unexplored. In this study, the scalable fabrication of the nanogaps was achieved using the LSR process; the extreme deformation behaviors of the nanometals were comprehensively investigated. The results indicated that the geometry of the primary structure and the LSR process will signally affect the microstructure evolution and deformation behavior of the sidewall during the LSR reshaping processes, and further affect the final geometrical morphology and optical properties of the generated nanogaps. The discovery of geometry-dependent deformation behaviors of the metallic structures is of great significance to the understanding of the mechanical deformation based nano-manufacturing processes.

Silver-decorated three-dimensional ZnO nanoflowers enhancing the electromagnetic coupling for ultrasensitive SERS detection of multi-pesticide residues

—The development of sensitive analytical methods is of prime importance for the detection of pesticide residues on the surfaces of fruits and vegetables at extremely low concentrations. Here, we synthesized Ag-decorated three-dimensional ZnO nanoflowers (ZnO@Ag) composed of ultrathin nanosheets as surface-enhanced Raman spectroscopy (SERS) substrates. Combined with the finite-difference time-domain (FDTD) method, it is proven that the ultrathin nanosheets greatly improve the electromagnetic coupling between the two metal nanoparticles due to the high refractive index of ZnO and generate new “hot spots”. The nanosheets also endow the incident light with multiple reflections to motivate the local electromagnetic field. The substrate presents high sensitivity and the enhancement factor was as high as 2.98 × 107 utilizing R6G as probe molecules. The detection concentration of thiram and malachite green (MG) solutions can reach 10−10 M and 10−9 M, respectively. For the real-life sample assays, the substrate can simultaneously detect the two pesticides on apple skin with high sensitivity. The research also reveals the importance of semiconductors toward the local electromagnetic field enhancement in noble metal-semiconductor substrates, benefiting the realization of highly sensitive SERS substrates and the wide application of the SERS technology in real-world scenarios.

Cascade amplification of optical absorption on III–V semiconductors via plasmon-coupled graphene

Plasmons in graphene (Gr) show many fascinating characteristics, such as dynamic tunability, strong field confinement of light-matter interaction, and highly responsive, which has been widely exploited for a number of applications, including photodetectors, optical modulators, and sensors. In this paper, graphene plasmons (GPs) were motivated by implanting Au nanoparticles (Au NPs) into Ta2O5 thin layers adjacent to the Gr film, and the strong localized surface plasmon resonance (LSPR) effect has been proposed and demonstrated by placing the GPs structure on a III–V semiconductor quantum well saturable absorber (SA). It has been substantiated that the heightened interaction between light and Gr via LSPR predominantly occurs through the mechanisms of resonant energy transfer and local electromagnetic field enhancement, rather than direct electron transfer. Significant improvement on the nonlinear characteristics of the GPs modulated III–V semiconductor SA has been observed with a 17.1% large modulation depth and obviously improved working stability. A 1550 nm passive mode-locked laser has been successfully constructed with a pulse width down to 523 fs by integrating the SA into the laser cavity. This work lays the foundation for the development of high-performance mode-locked lasers and also demonstrates the substantial enhancement of nonlinear optical properties of various materials not limited to III–V semiconductors provided by this GPs' modulated structure; hence, these findings offer extensive prospects for applications in various photonics and optoelectronic devices.

Dual-Plasmon Resonance Coupling Promoting Directional Photosynthesis of Nitrate from Air.

Photocatalysis, particularly plasmon-mediated photocatalysis, offers a green and sustainable approach for direct nitrogen oxidation into nitrate under ambient conditions. However, the unsatisfactory photocatalytic efficiency caused by the limited localized electromagnetic field enhancement and short hot carrier lifetime of traditional plasmonic catalysts is a stumbling block to the large-scale application of plasmon photocatalytic technology. Herein, we design and demonstrate the dual-plasmonic heterojunction (Bi/Csx WO3 ) achieves efficient and selective photocatalytic N2 oxidation. The yield of NO3 - over Bi/Csx WO3 (694.32 μg g-1 h-1 ) are 2.4 times that over Csx WO3 (292.12 μg g-1 h-1 ) under full-spectrum irradiation. The surface dual-plasmon resonance coupling effect generates a surge of localized electromagnetic field intensity to boost the formation efficiency and delay the self-thermalization of energetic hot carriers. Ultimately, electrons participate in the formation of ⋅O2 - , while holes involve in the generation of ⋅OH and the activation of N2 . The synergistic effect of multiple reactive oxygen species drives the direct photosynthesis of NO3 - , which achieves the overall-utilization of photoexcited electrons and holes in photocatalytic reaction. The concept that the dual-plasmon resonance coupling effect facilitates the directional overall-utilization of photoexcited carriers will pave a new way for the rational design of efficient photocatalytic systems.

Dual‐Plasmon Resonance Coupling Promoting Directional Photosynthesis of Nitrate from Air

AbstractPhotocatalysis, particularly plasmon‐mediated photocatalysis, offers a green and sustainable approach for direct nitrogen oxidation into nitrate under ambient conditions. However, the unsatisfactory photocatalytic efficiency caused by the limited localized electromagnetic field enhancement and short hot carrier lifetime of traditional plasmonic catalysts is a stumbling block to the large‐scale application of plasmon photocatalytic technology. Herein, we design and demonstrate the dual‐plasmonic heterojunction (Bi/CsxWO3) achieves efficient and selective photocatalytic N2 oxidation. The yield of NO3− over Bi/CsxWO3 (694.32 μg g−1 h−1) are 2.4 times that over CsxWO3 (292.12 μg g−1 h−1) under full‐spectrum irradiation. The surface dual‐plasmon resonance coupling effect generates a surge of localized electromagnetic field intensity to boost the formation efficiency and delay the self‐thermalization of energetic hot carriers. Ultimately, electrons participate in the formation of ⋅O2−, while holes involve in the generation of ⋅OH and the activation of N2. The synergistic effect of multiple reactive oxygen species drives the direct photosynthesis of NO3−, which achieves the overall‐utilization of photoexcited electrons and holes in photocatalytic reaction. The concept that the dual‐plasmon resonance coupling effect facilitates the directional overall‐utilization of photoexcited carriers will pave a new way for the rational design of efficient photocatalytic systems.

Fluorescent Microscopy of Hot Spots Induced by Laser Heating of Iron Oxide Nanoparticles

Determination of the iron oxide nanoparticles (IONPs) local temperature during laser heating is important in the aspect of laser phototherapy. We have carried out theoretical modeling of IONPs local electromagnetic (EM) field enhancement and heating under the laser action near individual IONPs and ensembles of IONPs with different sizes, shapes and chemical phases. For experimental determination of IONPs temperature, we used fluorescence thermometry with rhodamine B (RhB) based on its lifetime. Depending on the IONPs shape and their location in space, a significant change in the spatial distribution of the EM field near the IONPs surface is observed. The local heating of IONPs in an ensemble reaches sufficiently high values; the relative change is about 35 °C for Fe2O3 NPs. Nevertheless, all the studied IONPs water colloids showed heating by no more than 10 °C. The heating temperature of the ensemble depends on the thermal conductivity of the medium, on which the heat dissipation depends. During laser scanning of a cell culture incubated with different types of IONPs, the temperature increase, estimated from the shortening of the RhB fluorescence lifetime, reaches more than 100 °C. Such “hot spots” within lysosomes, where IONPs predominantly reside, lead to severe cellular stress and can be used for cell therapy.

Rebuildable Silver Nanoparticles Employed as Seeds for Synthesis of Pure Silver Nanopillars with Hexagonal Cross-Sections under Room Temperature

Silver nanopillars with strong plasmonic effects are used for localized electromagnetic field enhancement and regulation and have wide potential applications in sensing, bioimaging, and surface-enhanced spectroscopy. Normally, the controlled synthesis of silver nanopillars is mainly achieved using heterometallic nanoparticles, including Au nanobipyramids and Pd decahedra, as seeds for inducing nanostructure growth. However, the seed materials are usually doped in silver nanopillar products. Herein, the synthesis of pure silver nanopillars with hexagonal cross-sections is achieved by employing rebuildable silver nanoparticles as seeds. An environmentally friendly, stable, and reproducible synthetic route for obtaining silver nanopillars is proposed using sodium dodecyl sulfate as the surface stabilizer. Furthermore, the seed particles induce the formation of regular structures at different temperatures, and, specifically, room temperature is beneficial for the growth of nanopillars. The availability of silver nanoparticle seeds using sodium alginate as a carrier at different temperatures was verified. A reproducible method was developed to synthesize pure silver nanopillars from silver nanoparticles at room temperature, which can provide a strategy for designing plasmonic nanostructures for chemical and biological applications.

Ultrasensitive and Reliable SERS Chip Based on Facile Assembly of AgNPs on Porous LIG to Enhance the Local Electromagnetic Field

Low-concentration molecular detection is of great value in chemical analysis, environmental monitoring, biological analysis, and other trace detection fields. Surface-enhanced Raman scattering (SERS) is widely used in the analysis of low-concentration molecules with great potential for biological detection due to nondestructive measurement. However, detection uniformity and repeatability are challenges in the application of SERS, especially as regards ultrasensitive detection. Here, a AgNPs@LIG SERS chip with excellent sensitivity and uniformity was fabricated by electroplating Ag nanoparticles (AgNPs) on a laser-induced graphene (LIG) surface prepared on a polyimide (PI) film, which realized large-scale production with controllable shape and area. Such an SERS chip features a limit of detection (LOD) of 10–14 M, an enhancement factor (EF) of 3 × 1010, and fine uniformity (∼9.6% relative standard deviation) for rhodamine 6G, benefiting from excellent local electromagnetic field enhancement generated by the gap of AgNPs and excellent performance of porous LIG. Finally, the chip was applied to the detection of melamine with the LOD of 10–9 M, which confirmed the potential application value of the SERS chip for pollutant analysis. In addition, the preparation of the composite SERS chip is simple for mass production, which provides great potential for the development of ultrasensitive SERS biosensors for various biological and chemical analyses.

Detection of simple proteins by direct surface-enhanced Raman scattering based on the Hofmeister ion-specific effect

Surface-enhanced Raman scattering (SERS) spectroscopy has unique advantages in detecting biomolecules, but label-free determination of proteins with low scattering cross-sections remains challenging. In this study, such proteins’ SERS signals have been optimized using the Hofmeister effect between protein molecules and CsI solution at physiological concentrations (A 100 mmol/L Cesium iodide, CsI). Cs+ as chaotro cation ion has a complex interaction mechanism with protein, can not only deprive hydrated water molecules on the surface of protein but also penetrate into the hydrophobic interior of protein. In addition to the above advantages, I- in excess CsI solution with appropriate concentration can removes the interference of citric acid-based impurities on the surface of silver nanoparticles, and Cs+ in excess CsI solution attracts the aggregation of negatively charged silver nanoparticles and cause local electromagnetic field enhancement to achieve high sensitivity in protein detection. This has been combined with principal component analysis to perform a comprehensive analysis of several proteins. Molecular dynamics simulations have been performed to study the mechanism of interaction between CsI and proteins. In addition, the vibrational peak of water has been used as an internal standard to quantify the protein content, and a good linear relationship between peak intensity and concentration was obtained.

Reporter Molecules Embedded Au@Ag Core-Shell Nanospheres as SERS Nanotags for Cardiac Troponin I Detection

Rapid and accurate detection of acute myocardial infarction can improve patients' chances of survival. Cardiac troponin I (cTn I) is an important diagnostic biomarker for acute myocardial infarction. However, current immunoassays are insufficient to accurately measure cTn I, as they have limited detection sensitivity and are time-consuming. Surface-enhanced Raman scattering (SERS) is a brilliant fingerprints diagnostic technique characterised by ultrasensitivity, fast response, and qualitative and quantitative analysis capabilities. In this study, reporter molecules (4-Mercaptobenzoic acid, 4-MBA) embedded Au@Ag core-shell nanospheres as SERS nanotags were prepared for the detection of cTn I. As the Raman reporters were embedded between the core and the shell, they could be protected from the external environment and nanoparticle aggregation. Excellent SERS performances were obtained due to the enhanced local electromagnetic field in the gap of core and shell metals. In a standard phosphate buffered saline (PBS) environment, the limit of detection for cTn I was 0.0086 ng mL-1 (8.6 ppt) with a good linear relationship. The excellent Raman detection performance was attributed to the localized surface plasmon resonance effect and strong electromagnetic field enhancement effect produced by the gap between the Au core and the Ag shell. The SERS nanotags we prepared were facile to synthesize, and the analysis procedure could be completed quickly (15 min), which made the detection of cTn I faster. Therefore, the proposed SERS nanotags have significant potential to be a faster and more accurate tool for acute myocardial infarction diagnostics.

Ultra-high-Q resonances in terahertz all-silicon metasurfaces based on bound states in the continuum

High-Q metasurfaces have important applications in high-sensitivity sensing, low-threshold lasers, and nonlinear optics due to the strong local electromagnetic field enhancements. Although ultra-high-Q resonances of bound states in the continuum (BIC) metasurfaces have been rapidly developed in the optical regime, it is still a challenging task in the terahertz band for long years because of absorption loss of dielectric materials, design, and fabrication of nanostructures, and the need for high-signal-to-noise ratio and high-resolution spectral measurements. Here, a polarization-insensitive quasi-BIC resonance with a high-Q factor of 1049 in a terahertz all-silicon metasurface is experimentally achieved, exceeding the current highest record by 3 times of magnitude. And by using this ultra-high-Q metasurface, a terahertz intensity modulation with very low optical pump power is demonstrated. The proposed all-silicon metasurface can pave the way for the research and development of high-Q terahertz metasurfaces.

LSPR Tunable Ag@PDMS SERS Substrate for High Sensitivity and Uniformity Detection of Dye Molecules.

At present, the use of efficient and cost-effective methods to construct plasmonic surface-enhanced Raman scattering (SERS) substrates of high sensitivity, uniformity and reproducibility is still crucial to satisfy the practical application of SERS technology. In this paper, a localized surface plasmonic resonance (LSPR) tunable flexible Ag@PDMS substrate was successfully constructed by the low-cost bio-template-stripping method and magnetron sputtering technology. The theory proves that the local electromagnetic field enhancement and "hot spot" distribution is adjustable by modifying the size of the optical cavity unit in the periodicity nanocavity array structure. Experimentally, using rhodamine 6G (R6G) as the target analyte, the SERS performance of optimal Ag@PDMS substrate (Ag film thickness for 315 nm) was researched in detail, which the minimum detection limit was 10-11 M and the enhancement factor was calculated as 8.03 × 108, indicating its high sensitivity. The relative standard deviation (RSD) was calculated as 10.38%, showing that the prepared substrate had excellent electromagnetic field enhancement uniformity. At last, the trace detection of Crystal violet (CV, LOD = 10-9 M) and the simultaneous detection of three common dyes (R6G, CV and Methylene blue (MB) mixture) were also realized. This result suggests that the SERS substrate has a good application prospect in the quantitative and qualitative detection of dye molecules.

Uniform and Controllable Preparation of Ag–Au Composite Cascade Hollow Nanoarrays and Applications in SERS Trace Molecules Detection

In recent years, surface-enhanced Raman scattering (SERS) technique based on localized electromagnetic field enhancement on noble metal surfaces has received extensive attention in the field of trace molecule sensing and detection. However, in the process of practical application, the current SERS detection performance is still unable to achieve high detection sensitivity and high repeatability at the same time. In this paper, an efficient and controllable preparation method of Ag–Au composite cascade hollow nanoarray SERS substrates were provided based on nanoimprinting, conformal transfer and electrodeposition techniques. Crystal Violet (CV) was used as the probe molecule, and a low relative standard deviation of 6.65% of SERS intensity was obtained, and the detection concentration could be as low as 10[Formula: see text][Formula: see text]M, which can meet the needs of practical applications. The structure has multi-scale cascade characteristics, and significantly broadens the electromagnetic field enhancement characteristics of traditional single-scale configuration nanostructures on the premise of ensuring the uniformity of SERS detection. Such substrates can provide more abundant molecular adsorption sites, which is conducive to improving SERS detection sensitivity and stability. This method is universal, simple and with controllable and repeatable preparation process, which has good application potential in the construction of large-area uniform cascaded nanoarray structure SERS substrates.

Long-range interference of localized electromagnetic field enhancement in plasmonic nanofinger lattices

Sub-wavelength strongly confined electromagnetic field induced by surface plasmon resonance offers a promising method to enhance the light-matter interactions, which has wide applications in the fields of enhanced spectroscopy, photovoltaic conversion, and photocatalysis. For periodic metal nanostructures, the localized surface plasmon resonance (LSPR) can couple with the long-range diffractive interaction, causing a narrow linewidth. Here, we report a new family of plasmonic nanostructure fabricated through nanoimprint lithograph, which enables completely uniform, reproducible, and low-cost Au nanofinger multimer arrays with high aspect ratio at the manufacturing scale. Through adjusting the lattice spacing and the angle of incident light, the different collective coupling strengths between the diffraction modes and the LSPR of trimer or pentamer Au nanofingers arrays are observed experimentally by angle-resolved reflection spectroscopy. According to the numerical simulation based on the finite element method, the dynamic evolution of collective coupled modes is demonstrated. The typical surface charge distribution and electric field distribution of the coupled dipole resonance show a significant electromagnetic field enhancement. By adjusting the height of nanofingers, lattice spacing and gap size of adjacent nanofingers, the feasibility of the coupled modes is further investigated. This work provides an excellent candidate for the localization of light as chip-scale plasmonic devices.

A polarization-resolved ECL strategy based on the surface plasmon coupling effect of orientational Au nanobipyramids patterned structures

Here, we developed a polarization-resolved surface plasmon coupling electrochemiluminescence (ECL) strategy based on orientational Au nanobipyramids (Au NBPs) patterned structures. As the surface plasmonic materials, the Au NBPs with large localized electromagnetic field enhancement were used to construct the different patterned structures through the droplet evaporation induced assembly. The distinct morphology of the horizontal and vertical Au NBPs patterned structures provided the different plasmonic properties reflecting on resonance peak positions and polarized absorbance. As a result, the variations of the polarized ECL emission of SnS2 QDs have been regulated by the Au NBPs patterned structures via the surface plasmon coupling progress. Because of the superior polarization-resolved ECL performances, the sensing system was used to analyze the miRNA-21 and miRNA-205 expression level in tumor tissues of triple negative breast cancer patients. The satisfactory results indicated this polarization-resolved sensing strategy possessed great potential for clinical analysis.

Plasmon-enhanced photocatalytic cumulative effect on 2D semiconductor heterojunctions towards highly-efficient visible-light-driven solar-to-fuels conversion

The photocatalytic activity of a semiconductor is heavily influenced by its photocatalytic cumulative effect on the four consecutive photo-physiochemical processes, including (I) light harvesting, (II) charge separation, (III) charge migration, and (IV) charge utilization. However, it is still a tremendous challenge to enhance the photocatalytic cumulative effect by simultaneously sensitizing the total above I-IV processes of the semiconductor. Herein, we synthesized the well-designed plasmonic Au@Pt/CdS/C3N4 heterostructure through assembling Pt/CdS-selective-coated Au nanocubes onto the two dimensional (2D) ultrathin C3N4 nanosheets (NSs). We have also demonstrated that selectively coating CdS nanoparticle-clusters (NPCs) and Pt nanoparticles (NPs) onto the surfaces and edges of Au NCs could boost the II and III processes of the formed Au@Pt/CdS NCs based on the resonance energy transfer (RET) and “hot electron” transfer (HET) behaviors, respectively, due to the localized surface plasmon resonance (LSPR) of Au NCs. The assembly of the Au@Pt/CdS NCs onto the C3N4 NSs formed lots of 2D Au/CdS/C3N4 interface, where the Au-LSPR not only boosted the I process at the “type II” heterojunction regions of CdS/C3N4, but also improved the II process of C3N4 NSs via the local electromagnetic field enhancement (LEFE). Furthermore, the quasi-2D porous structure of CdS NPCs increased the surface active-sites at the 2D CdS/C3N4 interface, therefore enhancing the IV process. As such, when normalizing the effective active area as the Au@Pt/CdS/C3N4 hetero-interface region, the plasmonic heterostructure exhibited the ∼ 17.2-fold and ∼ 14.3-fold enhancements on the photocatalytic H2 evolution and CO2 reduction as compared to the CdS/C3N4 heterojunction, respectively.

Improved SERS detection of anionic pollutant with Ag Nanoparticles-decorated ZnAl layered double hydroxide nanosheets array

Enrichment is a valuable strategy to further improve the detection limit. In this work, ZnAl-layered double hydroxide (ZnAl-LDH) nanosheets array in situ synthesized on Al foil was used as the enrichment frame for surface-enhanced Raman spectroscopy (SERS) substrate to further improve the detection limit of anionic pollutant. High density of Ag nanoparticles (Ag-NPs) with an average diameter of 29 nm sputtered onto the surface of the ZnAl-LDH could create localized electromagnetic field enhancement for SERS detection. The as-prepared Ag-NPs@ZnAl-LDH composite substrates showed improved sensitivity to anionic pollutants methyl orange and erythrosin B, demonstrating the promising potentials to improve the detection limit of anion analytes based on SERS spectroscopy.

Oil-Free Gold Nanobipyramid@Ag Microgels as a Functional SERS Substrate for Direct Detection of Small Molecules in a Complex Sample Matrix.

Surface-enhanced Raman scattering (SERS) is a super-sensitive analysis technology based on the target molecular fingerprint information. The enhancement of local electromagnetic field of the SERS substrate would increase the target molecules' Raman intensity which adsorb on the surface of nanoparticles. However, the existing adhesive macromolecules in the complex mixed sample would interfere with the adsorption of small target molecules, and it weakens the Raman intensity of target molecules. Microgels are one of the potential materials to suppress the interference of adhesive macromolecules and to avoid the complex pretreatments. However, most of the current microgel synthesis methods involve complex operations with precise instrumentation or the interference of oil and organic reagents. In this work, a simple and oil-free method was proposed to synthesize the gold nanobipyramid (Au NBP)@Ag@hyaluronic acid microgel via the condensation reaction of carboxyl and amino groups. As a proof-of-concept demonstration for small-molecule detection, the rhodamine 6G (R6G) molecules were allowed to enter inside the microgel through the meshes and adsorb on the surface of Au NBP@Ag nanoparticles within 30 min, while the macromolecule (bovine serum albumin in this case) was retained outside the microgel in the meantime. In addition, under the combined action of lightning rod effect of Au NBP and surface plasmon resonance effect of silver render the microgels with high SERS activity. The synthetic Au NBP@Ag@hyaluronic acid microgels were applied to detect 6-thioguanine in the human serum without any pretreatment process, and it showed a high signal enhancement and stable SERS signal, which can satisfy the requirement of clinical diagnosis. These results show that the proposed microgels have potential applications in the field of point-of-care testing.