Spatial Analysis of Metal–PLGA Hybrid Microstructures Using 3D SERS Imaging

The incorporation of gold nanoparticles in biodegradable polymeric nanostructures with controlled shape and size is of interest toward different applications in nanomedicine. Properties of the polymer such as drug loading and antibody functionalization can be combined with the plasmonic properties of gold nanoparticles, to yield advanced hybrid materials. This study presents a new way to synthesize multicompartmental microgels, fibers, or cylinders, with embedded anisotropic gold nanoparticles. Gold nanoparticles dispersed in an organic solvent can be embedded within the poly(lactic‐co‐glycolic acid) (PLGA) matrix of polymeric microstructures, when prepared via electrohydrodynamic co‐jetting. Prior functionalization of the plasmonic nanoparticles with Raman active molecules allows for imaging of the nanocomposites by surface‐enhanced Raman scattering (SERS) microscopy, thereby revealing nanoparticle distribution and photostability. These exceptionally stable hybrid materials, when used in combination with 3D SERS microscopy, offer new opportunities for bioimaging, in particular when long‐term monitoring is required.     

Large‐Scale Fabrication of Three‐Dimensional Surface Patterns Using Template‐Defined Electrochemical Deposition

A new strategy to achieve large‐scale, three‐dimensional (3D) micro‐ and nanostructured surface patterns through selective electrochemical growth on monolayer colloidal crystal (MCC) templates is reported. This method can effectively create large‐area (>1 cm²), 3D surface patterns with well‐defined structures in a cost‐effective and time‐saving manner (<30 min). A variety of 3D surface patterns, including semishells, Janus particles, microcups, and mushroom‐like clusters, is generated. Most importantly, our method can be used to prepare surface patterns with prescribed compositions, such as metals, metal oxides, organic materials, or composites (e.g., metal/metal oxide, metal/polymer). The 3D surface patterns produced by our method can be valuable in a wide range of applications, such as biosensing, data storage, and plasmonics. In a proof‐of‐concept study, we investigated, both experimentally and theoretically, the surface‐enhanced Raman scattering (SERS) performance of the fabricated silver 3D semishell arrays.     

Arrays of Cone‐Shaped ZnO Nanorods Decorated with Ag Nanoparticles as 3D Surface‐Enhanced Raman Scattering Substrates for Rapid Detection of Trace Polychlorinated Biphenyls

A new, highly sensitive and uniform three‐dimensional (3D) hybrid surface‐enhanced Raman scattering (SERS) substrate has been achieved via simultaneously assembling small Ag nanoparticles (Ag‐NPs) and large Ag spheres onto the side surface and the top ends of large‐scale vertically aligned cone‐shaped ZnO nanorods (ZnO‐NRs), respectively. This 3D hybrid substrate manifests high SERS sensitivity to rhodamine and a detection limit as low as 10^?11 M to polychlorinated biphenyl (PCB) 77—a kind of persistent organic pollutants as global environmental hazard. Three kinds of inter‐Ag‐NP gaps in 3D geometry create a huge number of SERS “hot spots” that mainly contribute to the high SERS sensitivity. Moreover, the supporting chemical enhancement effect of ZnO‐NRs and the better enrichment effect ascribed to the large surface area of the substrate also help to achieve a lower detection limit. The arrays of cone‐shaped ZnO‐NRs decorated with Ag‐NPs on their side surface and large Ag spheres on the top ends have potentials in SERS‐based rapid detection of trace PCBs.     

Fabrication of a Macroporous Microwell Array for Surface‐Enhanced Raman Scattering

Here, a colloidal templating procedure for generating high‐density arrays of gold macroporous microwells, which act as discrete sites for surface‐enhanced Raman scattering (SERS), is reported. Development of such a novel array with discrete macroporous sites requires multiple fabrication steps. First, selective wet‐chemical etching of the distal face of a coherent optical fiber bundle produces a microwell array. The microwells are then selectively filled with a macroporous structure by electroless template synthesis using self‐assembled nanospheres. The fabricated arrays are structured at both the micrometer and nanometer scale on etched imaging bundles. Confocal Raman microscopy is used to detect a benzenethiol monolayer adsorbed on the macroporous gold and to map the spatial distribution of the SERS signal. The Raman enhancement factor of the modified wells is investigated and an average enhancement factor of 4 × 10⁴ is measured. This demonstrates that such nanostructured wells can enhance the local electromagnetic field and lead to a platform of ordered SERS‐active micrometer‐sized spots defined by the initial shape of the etched optical fibers. Since the fabrication steps keep the initial architecture of the optical fiber bundle, such ordered SERS‐active platforms fabricated onto an imaging waveguide open new applications in remote SERS imaging, plasmonic devices, and integrated electro‐optical sensor arrays.     

Nanogap Plasmonic Structures Fabricated by Switchable Capillary‐Force Driven Self‐Assembly for Localized Sensing of Anticancer Medicines with Microfluidic SERS

Nanogap plasmonic structures, which can strongly enhance electromagnetic fields, enable widespread applications in surface‐enhanced Raman spectroscopy (SERS) sensing. Although the directed self‐assembly strategy has been adopted for the fabrication of micro/nanostructures on open surfaces, fabrication of nanogap plasmonic structures on complex substrates or at designated locations still remains a grand challenge. Here, a switchable self‐assembly method is developed to manufacture 3D nanogap plasmonic structures by combining supercritical drying and capillary‐force driven self‐assembly (CFSA) of micropillars fabricated by laser printing. The polymer pillars can stay upright during solvent development via supercritical drying, and then can form the nanogap after metal coating and subsequent CFSA. Due to the excellent flexibility of this method, diverse patterned plasmonic nanogap structures can be fabricated on planar or nonplanar substrates for SERS. The measured SERS signals of different patterned nanogaps in fluidic environment show a maximum enhancement factor ≈8 × 10⁷. Such nanostructures in microchannels also allow localized sensing for anticancer drugs (doxorubicin). Resulting from the marriage of top‐down and self‐assembly techniques, this method provides a facile, effective, and controllable approach for creating nanogap enabled SERS devices in fluidic channels, and hence can advance applications in precision medicine.     

Nanogap‐Rich Au Nanowire SERS Sensor for Ultrasensitive Telomerase Activity Detection: Application to Gastric and Breast Cancer Tissues Diagnosis

Telomerase has attracted much attention as a universal cancer biomarker because telomerase is overexpressed in more than 85% of human cancer cells while suppressed in normal somatic cells. Since a strong association exists between telomerase activity and human cancers, the development of effective telomerase activity assay is critically important. Here, a nanogap‐rich Au nanowire (NW) surface‐enhanced Raman scattering (SERS) sensor is reported for detection of telomerase activity in various cancer cells and tissues. The nanogap‐rich Au NWs are constructed by deposition of nanoparticles on single‐crystalline Au NWs and provided highly reproducible SERS spectra. The telomeric substrate (TS) primer‐attached nanogap‐rich Au NWs can detect telomerase activity through SERS measurement after the elongation of TS primers, folding into G‐quadruplex structures, and intercalation of methylene blue. This sensor enables us to detect telomerase activity from various cancer cell lines with a detection limit of 0.2 cancer cells mL^?1. Importantly, the nanogap‐rich Au NW sensor can diagnose gastric and breast cancer tissues accurately. The nanogap‐rich Au NW sensors show strong SERS signals only in the presence of tumor tissues excised from 16 tumor‐bearing mice, while negligible signals in the presence of heated tumor tissues or normal tissues. It is anticipated that nanogap‐rich Au NW SERS sensors can be used for a universal cancer diagnosis and further biomedical applications including a diverse biomarker sensing.     

MUC1 Aptamer Targeted SERS Nanoprobes

Recently, surface‐enhanced Raman scattering (SERS) nanoprobes (NPs) have shown promise in the field of cancer imaging due to their unparalleled signal specificity and high sensitivity. This study reports the development of a DNA aptamer targeted SERS NP. Recently, aptamers are being investigated as a viable alternative to more traditional antibody targeting due to their low immunogenicity and low cost of production. A strategy is developed to functionalize SERS NPs with DNA aptamers, which target Mucin1 (MUC1) in human breast cancer (BC). Thorough in vitro characterization studies demonstrate excellent serum stability and specific binding of the targeted NPs to MUC1. In order to test their in vivo targeting capability, MUC1‐targeted SERS NPs are coinjected with nontargeted or blocked MUC1‐targeted SERS NPs in BC xenograft mouse models. A two‐tumor mouse model with differential expression of MUC1 (MDA‐MB‐468 and MDA‐MB‐453) is used to control for active versus passive targeting in the same animals. The results show that the targeted SERS NPs home to the tumors via active targeting of MUC1, with low levels of passive targeting. This strategy is expected to be an advantageous alternative to antibody‐based targeting and useful for targeted imaging of tumor extent, progression, and therapeutic response.     

Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media

The composition and intercellular interactions of tumor cells in the tissues dictate the biochemical and metabolic properties of the tumor microenvironment. The metabolic rewiring has a profound impact on the properties of the microenvironment, to an extent that monitoring such perturbations could harbor diagnostic and therapeutic relevance. A growing interest in these phenomena has inspired the development of novel technologies with sufficient sensitivity and resolution to monitor metabolic alterations in the tumor microenvironment. In this context, surface‐enhanced Raman scattering (SERS) can be used for the label‐free detection and imaging of diverse molecules of interest among extracellular components. Herein, the application of nanostructured plasmonic substrates comprising Au nanoparticles, self‐assembled as ordered superlattices, to the precise SERS detection of selected tumor metabolites, is presented. The potential of this technology is first demonstrated through the analysis of kynurenine, a secreted immunomodulatory derivative of the tumor metabolism and the related molecules tryptophan and purine derivatives. SERS facilitates the unambiguous identification of trace metabolites and allows the multiplex detection of their characteristic fingerprints under different conditions. Finally, the effective plasmonic SERS substrate is combined with a hydrogel‐based three‐dimensional cancer model, which recreates the tumor microenvironment, for the real‐time imaging of metabolite alterations and cytotoxic effects on tumor cells.     

Gold‐ and Silver‐Coated Barium Titanate Nanocomposites as Probes for Two‐Photon Multimodal Microspectroscopy

Improved multiphoton‐excited imaging and microspectroscopy require nanoprobes that can give different nonlinear optical signals. Here, composite nanostructures with a barium titanate core and a plasmonic moiety at their surface are synthesized and characterized. It is found that the core provides a high second‐order nonlinear susceptibility for sensitive second harmonic generation (SHG) imaging in living cells. As a second function in the two‐photon regime, the plasmonic part yields high local fields for resonant and nonresonant surface enhanced hyper Raman scattering (SEHRS). SEHRS complements the one‐photon surface enhanced Raman scattering (SERS) spectra that are also enhanced by the plasmonic shells. Barium titanate silver core–shell (Ag@BaTiO₃) composites are specifically suited for SEHRS and SHG excited at 1064 nm, while gold at barium titanate (Au@BaTiO₃) nanoparticles can be useful in a combination of SHG and SERS at lower wavelengths, here at 785 nm and 850 nm. The theoretical models show that the optical properties of the BaTiO₃ dielectric core depend on probing frequency, shape, size, and plasmonic properties of the surrounding gold nanoparticles so that they can be optimized for a particular type of experiment. These versatile, tunable probes give new opportunities for combined multiphoton probing of morphological structure and chemical properties of biosystems.     

Near‐Field Enhanced Plasmonic‐Magnetic Bifunctional Nanotubes for Single Cell Bioanalysis

Near‐field enhanced bifunctional plasmonic‐magnetic (PM) nanostructures consisting of silica nanotubes with embedded solid nanomagnets and uniformly dual‐surface‐coated plasmonic Ag nanoparticles (NPs) are rationally synthesized. The solid embedded sections of nanotubes provide single‐molecule sensitivity with an enhancement factor up to 7.2 × 10⁹ for surface‐enhanced Raman scattering (SERS). More than 2× SERS enhancement is observed from the hollow section compared to the solid section of the same nanotube. The substantial SERS enhancement on the hollow section is attributed to the dual‐sided coating of Ag NPs as well as the near‐field optical coupling of Ag NPs across the nanotube walls. Experimentation and modeling are carried out to understand the dependence of SERS enhancement on the NP sizes, junctions, and the near field effects. By tuning the aspect ratio of the embedded nanomagnets, the magnetic anisotropy of nanotubes can be readily controlled to be parallel or vertical to the long directions for nano‐manipulation. Leveraging the bifunctionality, a nanotube is magnetically maneuvered to a single living mammalian cell amidst many and its membrane composition is analyzed via SERS spectroscopy.     

Alloy Engineering in Few‐Layer Manganese Phosphorus Trichalcogenides for Surface‐Enhanced Raman Scattering

Manganese phosphorus trichalcogenides are widely used in the field of photocatalysis and magnetic studies due to their broadband gaps. Herein, an alloy engineering method for the few‐layer manganese phosphorus trichalcogenides (MnPS_3–xSe_x, 0 ≤ x ≤ 3) in surface‐enhanced Raman scattering (SERS) is reported. A new strategy, with the coupling of exciton resonance (µ_ex) and photoinduced charge transfer (PICT), is applied to screen out materials for SERS enhancement. According to the calculation of density functional theory, the bandgap of manganese phosphorus trichalcogenides (MnPS₃) can be adjusted to match the band energy of Rhodamine 6G molecules by alloy engineering. Furthermore, a series of few‐layer MnPS_3–xSe_x (0 ≤ x ≤ 3) are fabricated to study the PICT‐induced SERS behavior under resonance excitation. The good performance with a detection limit down to 10^?9 m indicates that the synergistic resonances between µ_ex and PICT are crucial to the enhancement.     

High‐Density Hotspots Engineered by Naturally Piled‐Up Subwavelength Structures in Three‐Dimensional Copper Butterfly Wing Scales for Surface‐Enhanced Raman Scattering Detection

Very recently, wing scales of natural Lepidopterans (butterflies and moths) manifested themselves in providing excellent three dimensional (3D) hierarchical structures for surface‐enhanced Raman scattering (SERS) detection. But the origin of the observed enormous Raman enhancement of the analytes on 3D metallic replicas of butterfly wing scales has not been clarified yet, hindering a full utilization of this huge natural wealth with more than 175 000 3D morphologies. Herein, the 3D sub‐micrometer Cu structures replicated from butterfly wing scales are successfully tuned by modifying the Cu deposition time. An optimized Cu plating process (10 min in Cu deposition) yields replicas with the best conformal morphologies of original wing scales and in turn the best SERS performance. Simulation results show that the so‐called “rib‐structures” in Cu butterfly wing scales present naturally piled‐up hotspots where electromagnetic fields are substantially amplified, giving rise to a much higher hotspot density than in plain 2D Cu structures. Such a mechanism is further verified in several Cu replicas of scales from various butterfly species. This finding paves the way to the optimal scale candidates out of ca. 175 000 Lepidopteran species as bio‐templates to replicate for SERS applications, and thus helps bring affordable SERS substrates as consumables with high sensitivity, high reproducibility, and low cost to ordinary laboratories across the world.     

Micro‐/Nanostructured Highly Crystalline Organic Semiconductor Films for Surface‐Enhanced Raman Spectroscopy Applications

The utilization of inorganic semiconductors for surface‐enhanced Raman spectroscopy (SERS) has attracted enormous interest. However, despite the technological relevance of organic semiconductors for enabling inexpensive, large‐area, and flexible devices via solution processing techniques, these π‐conjugated systems have never been investigated for SERS applications. Here for the first time, a simple and versatile approach is demonstrated for the fabrication of novel SERS platforms based on micro‐/nanostructured 2,7‐dioctyl[1]benzothieno[3,2‐b][1]benzothiophene (C8‐BTBT) thin films via an oblique‐angle vapor deposition. The morphology of C8‐BTBT thin films is manipulated by varying the deposition angle, thus achieving highly favorable 3D vertically aligned ribbon‐like micro‐/nanostructures for a 90° deposition angle. By combining C8‐BTBT semiconductor films with a nanoscopic thin Au layer, remarkable SERS responses are achieved in terms of enhancement (≈10⁸), stability (>90 d), and reproducibility (RSD < 0.14), indicating the great promise of Au/C8‐BTBT films as SERS platforms. Our results demonstrate the first example of an organic semiconductor‐based SERS platform with excellent detection characteristics, indicating that π‐conjugated organic semiconductors have a great potential for SERS applications.     

Highly Reproducible Surface‐Enhanced Raman Scattering on a Capillarity‐Assisted Gold Nanoparticle Assembly

A facile method based on capillarity‐assisted assembly is used to fabricate high‐performance surface‐enhanced Raman scattering (SERS) substrates employing clean Au nanoparticles (NPs). This method is better than micro‐channel way because the former may supply large‐area uniform assembly and overcome the uneven radial distribution. Such densely‐arranged assembly of Au NPs exhibits high reproducibility and large Raman enhancement factors of 3 × 10¹⁰, arising from strong electromagnetic field coupling induced by adjacent Au NPs. The spot‐to‐spot SERS signals show that the relative standard deviation (RSD) in the intensity of the main Raman vibration modes (1310, 1361, 1509, 1650 cm^?1) of Rhodamine 6G at a concentration of 1 × 10^?10 M are consistently less than 20%, demonstrating good spatial uniformity and reproducibility. The SERS signals of sudan dye at a 1 × 10^?8 M concentration also shows high reproducibility with a low RSD of <20%. Further, the assembly substrate is stable, retaining excellent uniformity and sensitivity after storage for months. This assembly strategy integrating the advantages of low‐cost production, high sensitivity, and reproducibility would significantly facilitate practical SERS detection.     

Facile Fabrication of High‐Density Sub‐1‐nm Gaps from Au Nanoparticle Monolayers as Reproducible SERS Substrates

The fabrication of ultrasmall nanogaps (sub‐1 nm) with high density is of significant interest and importance in physics, chemistry, life science, materials science, surface science, nanotechnology, and environmental engineering. However, it remains a challenge to generate uncovered and clean sub‐1‐nm gaps with high density and uniform reproducibility. Here, a facile and low‐cost approach is demonstrated for the fabrication of high‐density sub‐1‐nm gaps from Au nanoparticle monolayers as reproducible surface‐enhanced Raman scattering (SERS) substrates. Au nanoparticles with larger diameters possess lower surface charge, thus the obtained large‐area nanoparticle monolayer generates a high‐density of sub‐1‐nm gaps. In addition, a remarkable SERS performance with a 10¹¹ magnitude for the Raman enhancement is achieved for 120 nm Au nanoparticle monolayers due to the dramatic increase in the electromagnetic field enhancement when the obtained gap is smaller than 0.5 nm. The Au nanoparticle monolayer is also transferred onto a stretchable PDMS substrate and the structural stability and reproducibility of the high‐density sub‐1‐nm gaps in Au monolayer films are illustrated. The resultant Au nanoparticle monolayer substrates with an increasing particle diameter exhibit tunable plasmonic properties, which control the plasmon‐enhanced photocatalytic efficiency for the dimerization of p‐aminothiophenol. The findings reported here offer a new opportunity for expanding the SERS application.     

Self‐Assembled SERS Substrates with Tunable Surface Plasmon Resonances

The fabrication of surface‐enhanced Raman spectroscopy (SERS) substrates that are optimized for use with specific laser wavelength–analyte combinations is addressed. In order to achieve large signal enhancement, temporal stability, and reproducibility over large substrate areas at low cost, only self‐assembly and templating processes are employed. The resulting substrates consist of arrays of gold nanospheres with controlled diameter and spacing, properties that dictate the optical response of the structure. Tunability of the extended surface plasmon resonance is observed in the range of 520–1000 nm. It is demonstrated that the enhancement factor is maximized when the surface plasmon resonance is red‐shifted with respect to the SERS instrument laser line. Despite relying on self‐organization, site‐to‐site enhancement factor variations smaller than 10% are obtained.     

2D MXenes as a Promising Candidate for Surface Enhanced Raman Spectroscopy: State of the Art,Recent Trends,and Future Prospects

Surface-enhanced enhanced Raman spectroscopy (SERS) has emerged as a powerful analytical technique for ultrasensitive and label-free detection of chemical species, with numerous applications in various fields. Recently, 2D MXenes, have evoked substantial intrigue as promising substrates for SERS. Hence, a comprehensive understanding of the developments in the Raman effect and the mechanisms involved in SERS is highly crucial. The review reflects the advances, working principle, and dual mechanisms, including SERS's electromagnetic and chemical mechanisms. Noble metal nanostructures are highly prioritized as SERS substrates owing to their excellent sensitivity. However, due to certain disadvantages that they pose, metal-free SERS substrates with exceptional tunable properties are extensively researched in the current days. The combination of 2D MXenes and nanostructures can be effective in producing enhanced SERS signals. SERS performance of different MXene-based materials is emphasized. The performance of this combination is credited to their large surface-to-volume ratio, good electrical conductivity, and surface-terminated functionalities. The recent advancements in MXenes and MXenes-based heterostructures driven SERS sensing concerning the structural design of the material, its performance, and the mechanisms are studied. Finally, a detailed conclusion is provided with the challenges and future perspectives for designing 2D materials for efficient SERS sensors.     

Gold Nanoparticles Sliding on Recyclable Nanohoodoos—Engineered for Surface‐Enhanced Raman Spectroscopy

Robust, macroscopically uniform, and highly sensitive substrates for surface‐enhanced Raman spectroscopy (SERS) are fabricated using wafer‐scale block copolymer lithography. The substrate consists of gold nanoparticles that can slide and aggregate on dense and recyclable alumina/silicon nanohoodoos. Hot‐spot engineering is conducted to maximize the SERS performance of the substrate. The substrate demonstrates remarkably large surface‐averaged SERS enhancements, greater than 10⁷ (>10⁸ in hot spots), with unrivalled macroscopic signal uniformity as characterized by a coefficient of variation of only 6% across 4 cm. After SERS analyses, the nanohoodoos can be recycled by complete removal of gold via a one‐step, simple, and robust wet etching process without compromising performance. After eight times of recycling, the substrate still exhibits identical SERS performance in comparison to a new substrate. The macroscopic uniformity combined with recyclability at conserved high performance is expected to contribute significantly on the overall competitivity of the substrates. These findings show that the gold nanoparticles sliding on recyclable nanohoodoo substrate is a very strong candidate for obtaining cost‐effective, high‐quality, and reliable SERS spectra, facilitating a wide and simple use of SERS for both laboratorial and commercial applications.     

Significantly Increased Raman Enhancement on MoX2 (X = S,Se) Monolayers upon Phase Transition

2D transition metal dichalcogenide (TMD) materials have been recognized as active platforms for surface‐enhanced Raman spectroscopy (SERS). Here, the effect of crystal structure (phase) transition is shown, which leads to altered electronic structures of TMD materials, on the Raman enhancement. Using thermally evaporated copper phthalocyanine, solution soaked rhodamine 6G, and crystal violet as typical probe molecules, it is found that a phase transition from 2H‐ to 1T‐phase can significantly increase the Raman enhancement effect on MoX₂ (X = S, Se) monolayers through a predominantly chemical mechanism. First‐principle density functional theory calculations indicate that the significant enhancement of the Raman signals on metallic 1T‐MoX₂ can be attributed to the facilitated electron transfer from the Fermi energy level of metallic 1T‐MoX₂ to the highest occupied molecular orbital level of the probe molecules, which is more efficient than the process from the top of valence band of semiconducting 2H‐MoX₂. This study not only reveals the origin of the Raman enhancement and identifies 1T‐MoSe₂ and 1T‐MoS₂ as potential Raman enhancement substrates, but also paves the way for designing new 2D SERS substrates via phase‐transition engineering.     

3D Microfluidic Surface‐Enhanced Raman Spectroscopy (SERS) Chips Fabricated by All‐Femtosecond‐Laser‐Processing for Real‐Time Sensing of Toxic Substances

A novel all‐femtosecond‐laser‐processing technique is proposed for the fabrication of 2D periodic metal nanostructures inside 3D glass microfluidic channels, which have applications to real‐time surface‐enhanced Raman spectroscopy (SERS). In the present study, 3D glass microfluidic channels are fabricated by femtosecond‐laser‐assisted wet etching. This is followed by the space‐selective formation of Cu‐Ag layered thin films inside the microfluidic structure via femtosecond laser direct writing ablation and electroless metal plating. The Cu‐Ag films are subsequently nanostructured by irradiation with linearly polarized beams to form periodic surface structures. This work demonstrates that a double exposure to laser beams having orthogonal polarization directions can generate arrays of layered Cu‐Ag nanodots with dimensions as small as 25% of the laser wavelength. The resulting SERS microchip is able to detect Rhodamine 6G, exhibiting an enhancement factor of 7.3 × 10⁸ in conjunction with a relative standard deviation of 8.88%. This 3D microfluidic chip is also found to be capable of the real‐time SERS detection of Cd²⁺ ions at concentrations as low as 10 ppb in the presence of crystal violet. This technique shows significant promise for the fabrication of high performance microfluidic SERS platforms for the real‐time sensing of toxic substances with ultrahigh sensitivity.