Raman Active Dyes Research Articles

Detection of surface enhanced Raman scattering active hotspot using near field scanning optical microscopy

Hotspots are high-intensity electromagnetic zones that form, for example, at the interstitials of plasmonic nanoaggregates, resulting in a considerable rise in the enhancement factor. However, it is inevitable to achieve specific nanometric geometry as well as a suitable technique to capture the details of hotspots. We report near-field surface-enhanced Raman scattering (SERS) spectroscopy of a well-defined gold nanoaggregate of a few nanoparticles adsorbed with a small number of target analytes. A spectrally and spatially resolved SERS measurement setup using an aperture near-field scanning optical microscope (a-NSOM) facilitated the direct observation of localized electromagnetic (EM) fields at the interstitials through SERS. Correlated optical image and corresponding nanometric geometry were captured through the home-built a-NSOM setup. Near-field SERS spectra were recorded at different sites of interest. It was evident that the interstitial positioned at the center of the tetramer provided the most intense Raman scattering, implying the possibility of a SERS-active hotspot therein. SERS bands of the spectrum of the Raman-active dye Rhodamine 6G recorded at the same hotspot coincided well with those reported so far. It was noteworthy that most of the SERS bands in such scenery got enhanced. Such direct observation with high spatial resolution is indispensable to understanding the origin of localized EM fields at “hotspots” and the EM enhancement factor in the SERS process. A finite-difference time-domain (FDTD) analysis was carried out to validate the results.

Duplex Phenotype Detection and Targeting of Breast Cancer Cells Using Nanotube Nanoprobes and Raman Imaging.

We designed, synthesized, and characterized a Raman nanoprobe made of dye-sensitized single-walled carbon nanotubes (SWCNTs) that can selectively target biomarkers of breast cancer cells. The nanoprobe is composed of Raman-active dyes encapsulated inside a SWCNT, whose surface is covalently grafted with poly(ethylene glycol) (PEG) at a density of ∼0.7% per carbon. Using α-sexithiophene- and β-carotene-derived nanoprobes covalently bound to an antibody, either anti-E-cadherin (E-cad) or anti-keratin-19 (KRT19), we prepared two distinct nanoprobes that specifically recognize biomarkers on breast cancer cells. Immunogold experiments and transmission electron microscopy (TEM) images are first used to guide the synthesis protocol for higher PEG-antibody attachment and biomolecule loading capacity. The duplex of nanoprobes was then applied to target E-cad and KRT19 biomarkers in T47D and MDA-MB-231 breast cancer cell lines. Hyperspectral imaging of specific Raman bands allows for simultaneous detection of this nanoprobe duplex on target cells without the need for additional filters or subsequent incubation steps. Our results confirm the high reproducibility of the nanoprobe design for duplex detection and highlight the potential of Raman imaging for advanced biomedical applications in oncology.

SERS-based biosensor with Raman-active external responsive element for rapid determination of adenosine monophosphate

Phosphorylated adenosine derivatives are important biological molecules with diverse biological functions connected with the energetic balance of the cell, biosynthesis of cell components and regulation of protein activity. Measurement of these compounds provides information about the cell signalling in the body as well as the quantity of microorganisms in the environment. Surface-enhanced Raman spectroscopy (SERS) is an optical method that provides a unique spectrum of a substance at low concentrations. Specificity and limit of detection of SERS-based sensors can be increased drastically using nucleic acid aptamers and Raman-active dyes, respectively. Here we describe an adenosine monophosphate (AMP) biosensor based on AMP-dependent interaction between the well-known DNA aptamer for AMP and a novel Raman-active dye. The SERS intensity of novel Black Hole Quencher-2 (BHQ-2) derivatives was shown to be proportional to the charge of the molecule indicating electrostatic interactions with negatively charged colloidal silver nanoparticles. The novel derivative of BHQ-2 with two amine groups, BHQ-2-(NH2)2, binds an unpaired guanine stacked between guanine-guanine and guanine-adenine mismatches in DNA aptamer-AMP complex with KD = 26 nM as shown by 1H nuclear magnetic resonance, molecular docking and biolayer interferometry. The aptamer is pre-structured by AMP being folded in the conformation favorable for the interaction with BHQ-2-(NH2)2. This specific mechanism of the interaction allows designing of a SERS-based aptasensor with a limit of detection being as low as 3.4 nM of AMP and the dynamic range of nearly 5 orders – from 3.4 nM to 200 μM. The results illustrate a new approach to biosensors where DNA-interacting ligands act as external responsive elements providing an analyte-dependent SERS signal.

A Combination of Membrane Filtration and Raman-Active DNA Ligand Greatly Enhances Sensitivity of SERS-Based Aptasensors for Influenza A Virus.

Biosensors combining the ultrahigh sensitivity of surface-enhanced Raman scattering (SERS) and the specificity of nucleic acid aptamers have recently drawn attention in the detection of respiratory viruses. The most sensitive SERS-based aptasensors allow determining as low as 104 virus particles per mL that is 100-fold lower than any antibody-based lateral flow tests but 10–100-times higher than a routine polymerase chain reaction with reversed transcription (RT-PCR). Sensitivity of RT-PCR has not been achieved in SERS-based aptasensors despite the usage of sophisticated SERS-active substrates. Here, we proposed a novel design of a SERS-based aptasensor with the limit of detection of just 103 particles per ml of the influenza A virus that approaches closely to RT-PCR sensitivity. The sensor utilizes silver nanoparticles with the simplest preparation instead of sophisticated SERS-active surfaces. The analytical signal is provided by a unique Raman-active dye that competes with the virus for the binding to the G-quadruplex core of the aptamer. The aptasensor functions even with aliquots of the biological fluids due to separation of the off-target molecules by pre-filtration through a polymeric membrane. The aptasensor detects influenza viruses in the range of 1·103–5·1010 virus particles per ml.

Clusters-based silver nanorings: An active substrate for surface-enhanced Raman scattering

Plasmonic nanostructures, particularly irregular surfaces of ring-like silver (Ag) nanostructures are promising candidates in surface-enhanced Raman scattering (SERS) spectroscopy. In this work, clusters-based Ag nanorings have been fabricated and characterized as SERS-active substrates. The rim of the as-fabricated Ag nanorings was found neither discontinuous nor linear aggregation of nanoparticles. High-resolution field emission scanning electron microscopy (FESEM) revealed that the individual constituent clusters were different from each other, particularly in terms of size and shape in addition to the cases how such clusters were emerged as the edge of the nanoring. Considering the dimensions of the clusters and the arrangement of such clusters as nanorings, it was speculated that the local electromagnetic (EM) near-field distributions would excel and thus enhanced SERS signals would be achieved. Indeed, the inherent features of the nanorings facilitated to achieve SERS enhancement factors as high as 2.1 × 104. SERS-activity of as-fabricated Ag nanorings was confirmed using Rhodamine 6G (R6G) as Raman-active dyes and the enhancement was compared to those obtained from R6G adsorbed on Ag-ZnO/Glass and ZnO/Glass. To the best of our knowledge, this is the first attempt to explore the impact of localized EM near-field within the segments of nanorings through SERS spectroscopy. A model was designed resembling the nanorings under this investigation to simulate EM near-field distributions by finite difference time domain (FDTD) analysis. The dimensions of the model geometry were chosen according to the observations achieved by FESEM. To simplify the simulations, nanoobjects were considered spherical and organized in a periodic fashion, although the constituent clusters of Ag nanorings were found irregular in shape and arrangement. Since EM near-field distribution highly depends on interparticle gaps, three scenarios were implemented, such as, small gap in between two adjacent nanoobjects and adjacent nanoobjects in touch and overlapped. Each configuration was simulated and EM near-field distribution was extracted for s-, p- and 450 of incident polarizations followed by a plausible correlation to SERS enhancements. Such correlated investigations as well as clusters-based Ag nanorings not only inspire the ones to look for cost-effective SERS-active substrate, but also understand the underlying EM mechanism in SERS enhancements.

Electronic Preresonance Stimulated Raman Scattering Microscopy.

Optical microscopy has generated great impact for modern research. While fluorescence microscopy provides the ultimate sensitivity, it generally lacks chemical information. Complementarily, vibrational imaging methods provide rich chemical-bond-specific contrasts. Nonetheless, they usually suffer from unsatisfying sensitivity or compromised biocompatibility. Recently, electronic preresonance stimulated Raman scattering (EPR-SRS) microscopy was reported, achieving simultaneous high detection sensitivity and superb vibrational specificity of chromophores. With newly synthesized Raman-active dyes, this method readily breaks the optical color barrier of fluorescence microscopy and is well-suited for supermultiplex imaging in biological samples. In this Perspective, we first review previous utilizations of electronic resonance in various Raman spectroscopy and microscopy. We then discuss the physical origin and uniqueness of the electronic preresonance region, followed by quantitative analysis of the enhancement factors involved in EPR-SRS microscopy. On this basis, we provide an outlook for future development as well as the broad applications in biophotonics.

Introducing 12 new dyes for use with oligonucleotide functionalised silver nanoparticles for DNA detection with SERS

Oligonucleotide functionalised metallic nanoparticles (MNPs) have been shown to be an effective tool in the detection of disease-specific DNA and have been employed in a number of diagnostic assays. The MNPs are also capable of facilitating surface enhanced Raman scattering (SERS) enabling detection to become highly sensitive. Herein we demonstrate the expansion of the range of specific SERS-active oligonucleotide MNPs through the use of 12 new Raman-active monomethine and trimethine chalcogenopyrylium and benzochalcogenopyrylium derivatives. This has resulted in an increased ability to carry out multiplexed analysis beyond the current small pool of resonant and non-resonant Raman active molecules, that have been used with oligonucleotide functionalised nanoparticles. Each dye examined here contains a variation of sulphur and selenium atoms in the heterocyclic core, together with phenyl, 2-thienyl, or 2-selenophenyl substituents on the 2,2′,6, and 6′ positions of the chalcogenopyrylium dyes and 2 and 2′ positions of the benzochalcogenopyrylium dyes. The intensity of SERS obtained from each dye upon conjugate hybridisation with a complementary single stranded piece of DNA was explored. Differing concentrations of each dye (1000, 3000, 5000 and 7000 equivalents per NP-DNA conjugate) were used to understand the effects of Raman reporter coating on the overall Raman intensity. It was discovered that dye concentration did not affect the target/control ratio, which remained relatively constant throughout and that a lower concentration of Raman reporter was favourable in order to avoid NP instability. A relationship between the dye structure and SERS intensity was discovered, leaving scope for future development of specific dyes containing substituents favourable for discrimination in a multiplex by SERS. Methine dyes containing S and Se in the backbone and at least 2 phenyls as substituents give the highest SERS signal following DNA-induced aggregation. Principal component analysis (PCA) was performed on the data to show differentiation between the dye classes and highlight possible future multiplexing capabilities of the 12 investigated dyes.

Good vibrations for super-multiplexed imaging

Researchers optimize stimulated Raman scattering microscopy and combine it with a new panel of Raman-active dyes to enable 24-color bioimaging.

Multiplex single-cell quantification of rare RNA transcripts from protoplasts in a model plant system.

Here we demonstrate multiplex and simultaneous detection of four different rare RNA species from plant, Arabidopsis thaliana, using surface-enhanced Raman spectroscopy (SERS) and gold nanoprobes at single-cell resolution. We show the applicability of nanoparticle-based Raman spectroscopic sensor to study intracellular RNA copies. First, we demonstrate that gold-nanoparticles decorated with Raman probes and carrying specific nucleic acid probe sequences can be uptaken by the protoplasts. We confirm the internalization of gold nanoprobes by transmission electron microscopy, inductively-coupled plasma-mass spectrometry and fluorescence imaging. Second, we show the utility of a SERS platform to monitor individual alternatively spliced (AS) variants and miRNA copies within single cells. Finally, the distinctive spectral features of Raman-active dyes were exploited for multiplex analysis of AtPTB2, AtDCL2, miR156a and miR172a. Furthermore, single-cell studies were validated by invitro quantification and evaluation of nanotoxicity of gold probes. Raman tag functionalized gold nanosensors yielded an approach for the tracking of rare RNAs within the protoplasts. The SERS-based approach for quantification of RNAs has the capability to be a highly sensitive, accurate and discerning method for single-cell studies including AS variants quantification and rare miRNA detection in specific plant species.

Reversible Gating of Plasmonic Coupling for Optical Signal Amplification.

Amplification of optical signals is useful for a wide variety of applications, ranging from data signal transmission to chemical sensing and biomedical diagnostics. One such application in chemical sensing is surface-enhanced Raman scattering (SERS), an important technique for increasing the Raman signal using the plasmonic effect of enhanced electromagnetic fields associated with metallic nanostructures. One of the most important limitations of SERS-based amplification is the difficulty to reproducibly control the SERS signal. Here, we describe the design and implementation of a unique hybrid system capable of producing reversible gating of plasmonic coupling for Raman signal amplification. The hybrid system is composed of two subsystems: (1) colloidal magneto-plasmonic nanoparticles for SERS enhancement and (2) a micromagnet substrate with an externally applied magnetic field to modulate the colloidal nanoparticles. For this proof of concept demonstration, the nanoparticles were labeled with a Raman-active dye, and it was shown that the detected SERS signal could be reproducibly modulated by controlling the externally applied magnetic field. The developed system provides a simple, robust, inexpensive, and reusable device for SERS signal modulation. These properties will open up new possibilities for optical signal amplification and gating as well for high-throughput, reproducible SERS detection.

Alizarin dye based ultrasensitive plasmonic SERS probe for trace level cadmium detection in drinking water

Alizarin functionalized on plasmonic gold nanoparticle displays strong surface enhanced Raman scattering from the various Raman modes of Alizarin, which can be exploited in multiple ways for heavy metal sensing purposes. The present article reports a surface enhanced Raman spectroscopy (SERS) probe for trace level cadmium in water samples. Alizarin, a highly Raman active dye was functionalized on plasmonic gold surface as a Raman reporter, and then 3-mercaptopropionic acid, 2,6-pyridinedicarboxylic acid at pH 8.5 was immobilized on the surface of the nanoparticle for the selective coordination of the Cd(II). Upon addition of cadmium, gold nanoparticle provide an excellent hotspot for Alizarin dye and Raman signal enhancement. This plasmonic SERS assay provided an excellent sensitivity for cadmium detection from the drinking water samples. We achieved as low as 10ppt sensitivity from various drinking water sources against other Alkali and heavy metal ions. The developed SERS probe is quite simple and rapid with excellent repeatability and has great potential for prototype scale up for field application.

Au@pNIPAM SERRS Tags for Multiplex Immunophenotyping Cellular Receptors and Imaging Tumor Cells.

Detection technologies employing optically encoded particles have gained much interest toward clinical diagnostics and drug discovery, but the portfolio of available systems is still limited. The fabrication and characterization of highly stable surface-enhanced resonance Raman scattering (SERRS)-encoded colloids for the identification and imaging of proteins expressed in cells are reported. These plasmonic nanostructures are made of gold octahedra coated with poly(N-isopropylacrylamide) microgels and can be readily encoded with Raman active dyes while retaining high colloidal stability in biofluids. A layer-by-layer polyelectrolyte coating is used to seal the outer surface of the encoded particles and to provide a reactive surface for covalent conjugation with antibodies. The targeted multiplexing capabilities of the SERRS tags are demonstrated by the simultaneous detection and imaging of three tumor-associated surface biomarkers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), and homing cell adhesion molecule (CD44) by SERRS spectroscopy. The plasmonic microgels are able to discriminate tumor A431 (EGFR+/EpCAM+/CD44+) and nontumor 3T3 2.2 (EGFR-/EpCAM-/CD44+) cells while cocultured in vitro.

Star-shaped magnetite@gold nanoparticles for protein magnetic separation and SERS detection

A novel synthetic methodology for star shaped gold-coated magnetic nanoparticles is reported. The coating is performed in two steps: formation of gold nuclei at the surface of magnetite nanoparticles followed by growth of the gold nuclei into a complete star shaped shell. The star-shaped gold-coated magnetic nanoparticles thus obtained preserve the magnetic properties of the precursor magnetite nanoparticles, e.g. they can be easily separated with a magnet. In addition, the gold coating provides interesting optical properties while simultaneously allowing for biofunctionalization that may be advantageous for biological applications, such as (bio)detection via surface-enhanced Raman spectroscopy (SERS). As a proof-of-concept, a capping agent terminated with a nickel(II)-nitrilotriacetate group showing high affinity for histidine was used to modify the surface of the nanoparticles. The resulting star-shaped nanoparticles were used to selectively capture histidine-tagged maltose-binding protein from a crude cell extract. Finally, the performance of star shaped gold-coated magnetic nanoparticles as SERS platforms was demonstrated through the detection of Raman active dye (Astra Blue).

Wide range temperature detection with hybrid nanoparticles traced by surface-enhanced Raman scattering

We report on the fabrication of a class of surface-enhanced Raman scattering (SERS) active thermometers, which consists of 60 nm gold nanoparticles, encoded with Raman-active dyes, and a layer of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brush with different chain lengths. These SERS-active nanoparticles can be optimized to maintain spectrally silent when staying as single particles in dispersion. Increasing temperature in a wide range from 25 °C to 55 °C can reversibly induce the interparticle self-aggregation and turn on the SERS fingerprint signals with up to 58-fold of enhancement by taking advantage of the interparticle plasmonic coupling generated in the process of thermo-induced nanoparticles self-aggregation. Moreover, the most significative point is that these SERS probes could maintain their response to temperature and present all fingerprint signals in the presence of a colored complex. However, the UV-vis spectra can distinguish the differences faintly and the solution color shows little change in such complex mixture. This proof-of-concept and Raman technique applied here allow for dynamic SERS platform for onsite temperature detection in a wide temperature range and offer unique advantages over other detection schemes.

Surface-Enhanced Raman Spectroscopy-Based, Homogeneous, Multiplexed Immunoassay with Antibody-Fragments-Decorated Gold Nanoparticles

We report the development of a novel single-step, multiplexed, homogeneous immunoassay platform for sensitive detection of protein targets based on our realization of high surface-enhanced raman spectroscopy (SERS) signal enhancement by controlled assembly of SERS nanoparticles. An essential design of this platform is the use of gold nanoparticles or nanorods codecorated with specially reduced antibody half-fragments, nonfluorescent Raman-active dyes, and passivating proteins as the SERS nanoparticles. These nanoparticles offer a facile approach to accomplish orientational immobilization of antibodies, minimized interparticle distance, multicolor Raman fingerprint coding, low fluorescence background, as well as excellent biocompatibility and stability. Through sandwiched antibody-antigen interactions, controlled assembly of SERS nanoparticles is realized with a strong SERS signal achieved via plasmonic coupling, creating an immunoassay platform for rapid, sensitive, multiplexed quantification of proteins. This platform is demonstrated for reproducible quantification of three cytokines, interferon gamma, interleukin-2, and tumor necrosis factor alpha, with large signal-to-noise ratio. It is also successfully applied to multiplexed cytokine analysis for T cell secretion studies in complicated biological samples. The developed SERS immunoassay platform may create a simple but valuable tool for facilitating accurate validation and early detection of disease biomarkers as well as for point-of-care tests in clinical diagnostics.

Surfactant Size Effect on Surface-Enhanced Raman Scattering Intensity from Silver Nanoparticles

We report on the synthesis of two types of Ag nanoparticles (NPs) and the influence of adsorbed surfactant size on the NP surface for surface-enhanced Raman scattering (SERS) signals. Both particles were of similar size and morphology but were covered by surfactants of different sizes; one surfactant was sodium citrate (molecular weight: 258) and the other was sodium polyacrylate (molecular weight: 2100). For SERS measurement, 4-mecapobenzoic acid and 4-naphthalene thiol as Raman-active dyes were immobilized on the surface of each AgNP. The signals from Raman-active dyes on AgNPs covered with citrate displayed 10 times higher intensity than those from polyacrylate-stabilized AgNPs. Elemental analysis (EA) revealed that the average weight percentage of sulfur is 0.94 wt% and 0.12 wt% for citrate-stabilized and polyacrylate-stabilized AgNPs, respectively. The sulfur content difference was attributed to the size of the existing surfactant influencing the ligand exchange by steric hindrance and subsequently the amount of sulfur content of the particles. These experimental results suggest that the size of initial surfactant should be taken into account when synthesizing a metal particle for enhancing SERS signal.

Design of label-free, homogeneous biosensing platform based on plasmonic coupling and surface-enhanced Raman scattering using unmodified gold nanoparticles

Surface-enhanced Raman scattering (SERS) has emerged as a promising spectroscopic technique for biosensing. However, to design a SERS-based biosensor, almost all currently used methods involve the time-consuming and complicated modification of the metallic nanoparticles with the Raman active dye and biorecognition element, which restricts their widespread applications. Herein, we report a label-free, homogeneous and easy-to-operate biosensing platform for the rapid, simple and sensitive SERS detection by using the unmodified gold nanoparticles (Au NPs). This strategy utilizes the difference in adsorption property of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) on citrate-coated Au NPs. In the presence of dsDNA, the aggregation of Au NPs takes place after adding salt solution because the dsDNA cannot adsorb on the Au NPs to protect them from salt-induced aggregation. Such aggregation gives rise to the plasmonic coupling of adjacent metallic NPs and turns on the enhancement of the Raman scattering, displaying a strong SERS signal. In contrast, the ssDNA can adsorb on the Au NPs surface through strong electrostatic attraction and protect them from salt-induced aggregation, showing a weak SERS signal. This approach is not only straightforward and simple in design but also rapid and convenient in operation. The feasibility and universality of the design have been demonstrated successfully by the detection of DNA and Hg2+, and the assay possesses the superior signal-to-background ratio as high as ∼30 and excellent selectivity. The method can be extended to detect various analytes, such as other metal ions, proteins and small molecules by using the oligonucleotides that can selectively bind the analytes.

One-Phase Synthesis of Surface Modified Gold Nanoparticles and Generation of SERS Substrate by Seed Growth Method

In this study, we report a novel and facile single-phase synthesis of stable AuNP-CTAB(NA) conjugates with good dispersibility, bearing a bilayer of cationic surfactant, cetyltrimethylammonium bromide (CTAB) supported by N-nonylamine (NA) as a cosurfactant. We investigated AuNP-CTAB(NA) conjugates by (1)H NMR spectroscopy, UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). These studies suggest the presence of a CTAB bilayer on the nanoparticles surface forming an admicelle and NA embedded in the hydrophobic core of that bilayer. AuNP-CTAB(NA) conjugates remain dispersed in water even in the presence of high concentrations of salt and over a wide range of solution pHs. These conjugates further grow bigger when treated with additional AuCl(4)(-), CTAB, and NA in the presence of the mild reducing agent, hydroquinone (HQ). The larger AuNP-CTAB(NA)-1 conjugates serve as SERS (surface-enhanced Raman Scattering) substrate of Raman active dye even at nanomolar concentrations.

Evaluation of SERS labeling of CD20 on CLL cells using optical microscopy and fluorescence flow cytometry

Immunophenotyping of lymphoproliferative disorders depends on the effective measurement of cell surface markers. The inherent light-scattering properties of plasmonic nanoparticles (NPs) combined with recent developments in NP design may confer significant advantages over traditional fluorescence probes. We report and evaluate the use of surface-enhanced Raman scattering (SERS) gold NPs (AuNPs) conjugated to therapeutic rituximab antibodies for selective targeting of CD20 molecules. SERS AuNPs were prepared by adsorbing a Raman-active dye onto the surface of 60 nm spherical AuNPs, coating the particles with 5 kDa polyethylene glycol, and conjugating rituximab to functional groups on polyethylene glycol. The effective targeting of CD20 on chronic lymphocytic leukemia cells by rituximab-conjugated SERS AuNPs was evaluated by dark-field imaging, Raman spectroscopy, and flow cytometry with both competitive binding and fluorescence detection procedures. Evidence of CD20 clustering within approximately 100 nm was observed. From the Clinical EditorThis study discusses the use of surface enhancement Raman scattering (SERS)-based plasmonic gold nanoparticles, which can be used for cell specific labeling. In this example rituximab, a commercially available CD20 humanized monoclonal antibody is used. Dark field imaging, Raman spectroscopy and flow cytometry was utilized to demonstrate the sensitive labeling capability of these gold nanoparticle based hybrid nanodevices.

SERS-Active Nanoparticles for Sensitive and Selective Detection of Cadmium Ion (Cd2+)

We report a new class of turn-on surface enhanced Raman scattering (SERS) sensors for the sensitive and selective detection of cadmium ion (Cd2+) by taking advantage of the interparticle plasmonic coupling generated in the process of Cd2+-selective nanoparticle self-aggregation. The SERS-active nanoparticles consist of 41-nm gold nanoparticles, encoded with a Raman-active dye through a disulfide anchoring group, and a layer of Cd2+-chelating polymer brush coating grafted on the nanoparticle via surface-initiated atom transfer radical polymerization. These SERS nanoparticles are optimized to remain spectrally silent when staying as single particles. Addition of Cd2+ leads to interparticle self-aggregation and immediately turns on the SERS fingerprint signal with up to 90-fold of signal enhancement. The selectivity of the SERS nanoparticle for Cd2+ was also examined, showing that various common metal ions cannot induce interparticle self-aggregation and the turn-on of SERS signal. In contrast to nanoparticle-based colorimetric assays, the SERS probe is also capable of detecting Cd2+ in heavily colored samples.