Surface Enhanced Raman Spectroscopy Sensor Research Articles

Surface-Enhanced Raman Spectroscopy Sensor Integrated with Ag@ZIF-8@Au Core-Shell-Shell Nanowire Membrane for Enrichment, Ultrasensitive Detection, and Inactivation of Bacteria in the Environment.

A core-shell-shell sandwich material is developed with silver nanowires as the core, ZIF-8 as an inner shell, and gold nanoparticles as the outer shell, namely, Ag@ZIF-8@Au nanowires (AZA-NW). Then, the synthesized AZA-NW is transformed into a surface-enhanced Raman spectroscopy (SERS) sensor (named M-AZA) by the vacuum filtration method and used to enrich, detect, and inactivate traces of bacteria in the environment. The M-AZA sensor has three main functions: (1) trace bacteria are effectively enriched, with an enrichment efficiency of 91.4%; (2) ultrasensitive detection of trace bacteria is realized, with a minimum detectable concentration of 1 × 101 CFU/mL; (3) bacteria are effectively killed up to 92.4%. The shell thickness of ZIF-8 (5-75 nm) is controlled by adjusting the synthesis conditions. At an optimum shell thickness of 15 nm, the effect of gold nanoparticles and ZIF-8 shell on the sensor's stability, SERS activity, and antibacterial performance is investigated. The simulation of the SERS sensor using the finite difference time domain (FDTD) method is consistent with the experimental results, theoretically demonstrating the role of the gold nanoparticles and the ZIF-8 shell. The sensor also shows excellent stability, safety, and generalizability. The campus water sample is then tested on-site by the M-AZA SERS sensor, indicating its potential for practical applications.

Development of aptamer surface-enhanced Raman spectroscopy sensor based on Fe3O4@Pt and Au@Ag nanoparticles for the determination of acetamiprid.

As a common chlorinated nicotinic pesticide with high insecticidal activity, acetamiprid has been widely used for pest control. However, the irrational use of acetamiprid will pollute the environment and thus affect human health. Therefore, it is crucial to develop a simple, highly sensitive, and rapid method for acetamiprid residue detection. In this study, the capture probe (Fe3O4@Pt-Aptamer) was connected with the signal probe (Au@DTNB@Ag CS-cDNA) to form an assembly with multiple SERS-enhanced effects. Combined with magnetic separation technology, a SERS sensor with high sensitivity and stability was constructed to detect acetamiprid residue. Based on the optimal conditions, the SERS intensity measured at 1333cm-1 is in relation to the concentration of acetamiprid in the range 2.25 × 10-9-2.25 × 10-5M, and the calculated limit of detection (LOD) was 2.87 × 10-10M. There was no cross-reactivity with thiacloprid, clothianidin, nitenpyram, imidacloprid, and chlorpyrifos, indicating that this method has good sensitivity and specificity. Finally, the method was applied to the detection of acetamiprid in cucumber samples, and the average recoveries were 94.19-103.58%, with RSD < 2.32%. The sensor can be used to analysereal samples with fast detection speed, high sensitivity, and high selectivity.

Preparation of Flower-like Nanosilver Based on Bioderived Caffeic Acid for Raman Enhancement and Dye Degradation.

In this study, a simple, green, and low-cost room temperature synthesis of broccoli-like silver nanoflowers (AgNF) with a particle size of about 300-500 nm was developed using plant-derived caffeic acid as a reducing agent and polyvinylpyrrolidone as a dispersant under ultrasound assistance. The flower clusters covered by small nanocrystals of 20-50 nm significantly enhance the electromagnetic field signals. AgNF was deposited on the surface of silicon wafers as a surface-enhanced Raman spectroscopy sensor for the detection of probe molecules such as rhodamine 6G (R6G) and malachite green with high sensitivity, homogeneity, and reproducibility. AgNF was deposited on cotton fabrics in the form of composites to catalyze the degradation of dye pollutants such as R6G, MG, and methyl orange in the presence of sodium borohydride. 0.1 g of AgNF/cotton fabric could assist 15 mmol/L NaBH4 to achieve over 90% degradation of various dyes as well as a high concentration of dyes in 12 min with good reusability and recyclability. The AgNF synthesized in this work can not only monitor the type and amounts of pollutants (dyes) in wastewater but also catalyze the rapid degradation of dyes, which is expected to be valuable for industrial applications.

Surface enhanced Raman spectroscopy sensor based on silver nanoparticles/multi wall carbon nanotubes for ultrasensitive detection of cholesterol

Cholesterol is vital for living things because of an important part of cell membranes, as well as one of the basic components of brain and nerve cells. However, cholesterol must be at an optimum level. If it is below or above this level, it is a marker of many various diseases. Therefore, the detection of cholesterol amount is very important. Herein, MWCNTs were synthesized and AgNPs were grown on their surfaces. Thus, AgNP/MWCNT hybrid material was obtained. The AgNP/MWCNTs were used as surface enhancement Raman scattering (SERS) substrate to quantify the cholesterol molecule. High SERS enhancement of AgNP/MWCNT, specific SERS sensing platform and high sensitive SERS substrate were proposed to determine and monitor cholesterol molecule. AgNP/MWCNT substrate was studied in the concentration range of 10−3–10−10 M and the limit of detection (LOD) was calculated as 3.24 × 10−11 M. In addition, the enhancement factor (EF) was determined as 6.21 × 109. As a result, it was reported in this study that cholesterol molecule can be determined with excellent accuracy, precision and sensitive by using AgNP/MWCNT substrate and therefore it can provide great potential in clinical diagnosis and health management.

Textile Electronics with Laser-Induced Graphene/Polymer Hybrid Fibers.

The concept of wearables is rapidly evolving from flexible polymer-based devices to textile electronics. The reason for this shift is the ability of textiles to ensure close contact with the skin, resulting in comfortable, lightweight, and compact "always with you" sensors. We are contributing to this polymer-textile transition by introducing a novel and simple way of laser intermixing of graphene with synthetic fabrics to create wearable sensing platforms. Our hybrid materials exhibit high electrical conductivity (87.6 ± 36.2 Ω/sq) due to the laser reduction of graphene oxide and simultaneous laser-induced graphene formation on the surface of textiles. Furthermore, the composite created between graphene and nylon ensures the durability of our materials against sonication and washing with detergents. Both of these factors are essential for real-life applications, but what is especially useful is that our free-form composites could be used as-fabricated without encapsulation, which is typically required for conventional laser-scribed materials. We demonstrate the exceptional versatility of our new hybrid textiles by successfully recording muscle activity, heartbeat, and voice. We also show a gesture sensor and an electrothermal heater embedded within a single commercial glove. Additionally, the use of these textiles could be extended to personal protection equipment and smart clothes. We achieve this by implementing self-sterilization with light and laser-induced functionalization with silver nanoparticles, which results in multifunctional antibacterial textiles. Moreover, incorporating silver into such fabrics enables their use as surface-enhanced Raman spectroscopy sensors, allowing for the direct analysis of drugs and sweat components on the clothing itself. Our research offers valuable insights into simple and scalable processes of textile-based electronics, opening up new possibilities for paradigms like the Internet of Medical Things.

SERS-active substrates using DVD-R coated in silver thin films: A preliminary study for detection of commercial glyphosate

Glyphosate (GLP) is the herbicide with the highest level of global commercialization and historical use. Even though numerous studies have found this substance to be harmless, current research demonstrates that GLP might affect human health. For this reason, researcher efforts are concentrating on alternatives for analytical quantification, such as Surface Enhanced Raman Spectroscopy (SERS). In this work, a DVD-R@AgNPs SERS substrate was produced by the Cathodic Cage Plasma Deposition (CCPD) technique, which allowed a thin film layer deposition of silver nanoparticles (AgNPs) on the PC grating structure from Digital Video/Versatile Disc Recordable (DVD-R). Scanning Electron Microscopy with energy-dispersive X-ray spectroscopy was used to characterize the substrate and chemical changes on the surface after AgNPs deposition. The DVD-R@AgNPs substrate was used to detect standard crystal violet (CV), GLP, and RoundupTM GLP (GLP-RU) using Raman Spectroscopy. The CV was used as a control sample for SERS measurement, allowing the calculation of the substrate enhancement factor, which was in the order of ∼ 105. To evaluate the efficiency of the SERS substrate, the limit of detection was calculated and showed values of ∼ 10-10 mol/L for CV, 10-7 and 10-8 mol/L for GLP, and 10-6 mol/L for GLP-RU. Thus, the DVD-R@AgNPs SERS sensor is a low-cost substrate that analyzes traces of pesticides such as commercial GLP, demonstrating high SERS sensitivities and many applications.

Controllable-Swelling Microneedle-Assisted Ultrasensitive Paper Sensing Platforms for Personal Health Monitoring.

Microneedle (MN) patches, which allow the extraction of skin interstitial fluid (ISF) without a pain sensation, are powerful tools for minimally invasive biofluid sampling. Herein, an MN-assisted paper-based sensing platform that enables rapid and painless biofluid analysis with ultrasensitive molecular recognition capacity is developed. First, a controllable-swelling MN patch is constructed through the engineering of a poly(ethylene glycol) diacrylate/methacrylated hyaluronic acid hydrogel; it combines rapid, sufficient extraction of ISF with excellent structural integrity. Notably, the analyte molecules in the needles can be recovered into a moist cellulose paper through spontaneous diffusion. More importantly, the paper can be functionalized with enzymatic colorimetric reagents or a plasmonic array, enabling a desired detection capacity-for example, the use of paper-based surface-enhanced Raman spectroscopy sensors leads to label-free, trace detection (sub-ppb level) of a diverse set of molecules (cefazolin, nicotine, paraquat, methylene blue). Finally, nicotine is selected as a model drug to evaluate the painless monitoring of three human volunteers. The changes in the nicotine levels could be tracked, with the levels varying significantly in response to metabolism of the drug in the different volunteers. This as-designed minimally invasive sensing system should open up new opportunities for precision medicine, especially for personal healthcare monitoring. This article is protected by copyright. All rights reserved.

Coupling of plasmonic hot spots with shurikens for superchiral SERS-based enantiomer recognition.

Detection of enantiomers is a challenging problem in drug development as well as environmental and food quality monitoring where traditional optical detection methods suffer from low signals and sensitivity. Application of surface enhanced Raman scattering (SERS) for enantiomeric discrimination is a powerful approach for the analysis of optically active small organic or large biomolecules. In this work, we proposed the coupling of disposable chiral plasmonic shurikens supporting the chiral near-field distribution with SERS active silver nanoclusters for enantio-selective sensing. As a result of the plasmonic coupling, significant difference in SERS response of optically active analytes is observed. The observations are studied by numerical simulations and it is hypothesized that the silver particles are being excited by superchiral fields generated at the surface inducing additional polarizations in the probe molecules. The plasmon coupling phenomena was found to be extremely sensitive to slight variations in shuriken geometry, silver nanostructured layer parameters, and SERS excitation wavelength(s). Designed structures were able to discriminate cysteine enantiomers at concentrations in the nanomolar range and probe biomolecular chirality, using a common Raman spectrometer within several minutes. The combination of disposable plasmonic substrates with specific near-field polarization can make the SERS enantiomer discrimination a commonly available technique using standard Raman spectrometers.

Rapid and ultralow level SERS detection of ethylparaben using silver nanoprisms functionalized sea urchin-like Zinc oxide nanorod arrays for food safety analysis

Surface enhanced Raman spectroscopy (SERS) offers a tremendous opportunity to sense food additives in a fast, flexible and ultrasensitive mode. In the present study, we have designed silver nanoprism (AgNPr) functionalized Zinc Oxide (ZnO) hetero architectures for SERS sensing of food preservatives such as ethylparaben (EP). ZnO nanorods (NRs) were found to be formed which organized into sea urchin-like morphology via a facile hydrothermal process. While varying the growth time from 3 to 72 h, the nanorod length was found to be enhanced from 500 to 1900 nm range. The effect of morphology of as-fabricated substrates was well correlated with absorption and vibrational modes. Moreover, silver nanoprisms with peculiar triangular morphology with a size range of 20–80 nm were synthesized for functionalizing ZnO arrays; whose incorporation was further confirmed by EDS and XPS analysis. SERS studies demonstrated that AgNPr/ZnO NRs assembly exhibited synergistic Raman signal enhancement, which was modulated by the length of the nanorods. The highest SERS activity was exhibited by substrates with ∼1500 nm nanorod length. The reproducibility and reusability of optimized AgNPr/ZnO NRs substrates were demonstrated as well. The developed sensor exhibited highly specific real-time sensing of EP with sensitivity down to pico-molar levels; could be considered a good candidate for rapid, in situ identification of food preservatives for food safety applications. • Hierarchical zinc oxide-silver nanoprism arrays were designed as SERS sensors. • Morphological properties of sensor was well correlated with SERS performance. • Nanorod lengths of ∼1500 nm demonstrated highest signal enhancement. • Food additive like ethylparaben (EP) was detected down to pico-molar levels. • The optical sensing of EP was evidenced with high sensitivity and reusability.

Detection of stx2 from Shiga toxin-producing Escherichia coli (STEC) by a surface enhanced Raman spectroscopy (SERS) sensor using recycled silicon chips

In this research, a selective, cost-efficient, and highly sensitive Ag nanostructure Surface Enhanced Raman Spectroscopy (SERS) sensor was developed as a methodological approach to rapidly detect a targetss-DNA (stx2) in STEC (Shiga toxin-producing Escherichia coli). The Ag nanostructure-based SERS substrate was functionalized by two types of thiols: thiol-ss-DNA for bonding target ss-DNA and 6-Mercapto-1-hexanol (HS(CH2)6OH) for blocking the Ag nanostructure surface. Methylene Blue (MB) was used as a Raman marker to quantify target ss-DNA, as well as a model molecule to characterize the electrodeposited Ag nanostructure SERS substrate. Ag nanostructure SERS substrates showed good sensitivity and repeatability towards MB detection, with a LOD = 0.3158 μM, and RSD = 12.48% (at 45 different random points for 0.1 μM MB). More importantly, the Ag nanostructure/ss-DNA SERS substrate showed good selectivity towards STEC O157 stx2 target DNA, as well as good linearity and sensitivity towards its detection in a buffer solution. A limit of detection of 0.4900 aM and a wide linear range from 1 aM to 100 pM were demonstrated. The SERS sensors were able to identify target DNA (stx2) in a STEC strain and the study showed proof of principle that SERS substrate has potential as a cost-effective, highly selective, highly sensitive DNA and bacteria sensor without the aid of DNA amplification. With further development and validation, this methodological approach has the potential for point-of-use detection for instance on a farm or in the food industry.

Rapid and ultra-sensitive detection of pork DNA with surface enhanced Raman spectroscopy for onsite food quality inspection

Determination of pork DNA is essential to avoid the serious allergens imposed by it as well as for halal authentication for certain community. The needed sensor should be able to identify the pork DNA in rapid way and sensitive to ultra-low molarity detection. In this work we developed a surface enhanced Raman spectroscopy sensor (SERS) using silver nanoparticles (AgNPs) on Si matrix. A deep investigation of the effect of the laser wavelength on the sensing efficiency has been performed. Wavelength dependent sensing mechanisms are deliberately studied in the current research. Further the selectivity of sensor towards Pork DNA discrimination is exhibited with Chicken DNA analysis. The developed SERS sensor identifies the Pork DNA down to 13.6 fg/ μL proving its excellent sensitivity. The statistical outfit studies with regard to the developed sensor shows the low values of RSD (∼3%) adding advantage of the developed SERS sensor biosensor. The SERS sensor will definitely serve to be an excellent fast, selective and sensitive tool for onsite screening of meat products to cease the adulteration.

Separable surface enhanced Raman spectroscopy sensor platformed by HPTLC for facile screening of malachite green in fish

Facile and effective coupling of SERS sensor to chromatographic tools has been an attractive goal in the field of food analytical chemistry for years. Platformed by HPTLC, a separable SERS sensor was developed in this study and its analytical power was exemplarily evaluated by screening trace malachite green in fish. To enable enough detectability and reproducibility of SERS measurements, a flexible substrate based on the hybrid of AgNP and glass fiber paper was easily fabricated. Meanwhile, the crude extract of fish muscle was separated on the aluminum foil backed HPTLC plate, resulting in spiral isolation of the analyte from co-extracted matrix. Guided by the visible standard in parallel, bands of interest were thereafter transferred to the eluent by a handy puncher. Jointly with the as-prepared flexible substrate, the band eluent was measured by Raman spectroscopy, responding sensitive and characteristic fingerprint signals. Meanwhile, performances of the established SERS sensor were also examined, showing adequate detectability (LOD < 10 μg/kg), precision (RSD%<11.8%) and linearity (R2 = 0.9975 from 0.05 to 10 ng/band) for screening purpose. Apart from that, the analysis robustness for practical application was further validated with fish sample, giving spike-recovery rates from 78.8 to 87.3%. This work demonstrated that HPTLC platformed SERS sensor can reach an ideal balance between efficiency, throughput and reliability, and therefore might be a promising tool especially suitable for screening trace contaminants in sophisticated mixtures.

DNA Origami-Enabled Plasmonic Sensing.

The reliable programmability of DNA origami makes it an extremely attractive tool for bottom-up self-assembly of complex nanostructures. Utilizing this property for the tuned arrangement of plasmonic nanoparticles holds great promise particularly in the field of biosensing. Plasmonic particles are beneficial for sensing in multiple ways, from enhancing fluorescence to enabling a visualization of the nanoscale dynamic actuation via chiral rearrangements. In this Perspective, we discuss the recent developments and possible future directions of DNA origami-enabled plasmonic sensing systems. We start by discussing recent advancements in the area of fluorescence-based plasmonic sensing using DNA origami. We then move on to surface-enhanced Raman spectroscopy sensors followed by chiral sensing, both utilizing DNA origami nanostructures. We conclude by providing our own views on the future prospects for plasmonic biosensors enabled using DNA origami.

Ultra-sensitive surface enhanced Raman spectroscopy sensor for in-situ monitoring of dopamine release using zipper-like ortho-nanodimers

Accurate quantitative detection of dopamine (DA) in blood is essential for the early diagnosis and the pathogenesis analysis of dopaminergic dysfunction, which still remains a great challenge because of the extremely low concentration in patients. Using our previously reported DNA-assisted synthesis of ortho-nanodimers (DaSON) strategy, a microfluidic surface enhanced Raman spectroscopy (SERS) biosensor for the ultrasensitive and reliable detection of DA in serum was demonstrated by modifying SERS probes with DA aptamers in a specific orientation to form zipper-like ortho-nanodimers. The uniform 1-nm gap in zipper-like ortho-nanodimers endows the SERS sensor with ultrahigh sensitivity and high accuracy for the detection of DA. The limit of detection is as low as 10 aM in phosphate buffer saline and 10 fM in serum, which is about two orders of magnitude lower than that of previous methods. Using a single microfluidic chip containing a 3D cell culture unit, quantitatively in-situ monitoring of extracellular DA released from living neurons under different medications was first realized. Quantification of DA in human blood samples was also achieved with the recoveries ranging from 87.5% to 123.7%. Given the difficulty of DA quantification in complex physiological samples, our developed SERS sensor provides an appealing tool for in-vitro investigating of neurological processes and clinical examination of dopaminergic disorders.

Nanocellulose-based Surface-enhanced Raman spectroscopy sensor for highly sensitive detection of TNT

Surface-enhanced Raman scattering (SERS) has undergone an important development in the detection and identification of extremely low traces of explosives over the past few years. Here we fabricated a new type of three-dimensional (3D) SERS sensors by loading AuNR@AgNCs on bacterial cellulose aerogels for the detection of 2, 4, 6-trinitrotoluene (TNT). The aerogel substrates with hierarchical pore structure are favored by the construction of dense 3D hot-spot distribution and the enrichment of TNT molecules. The retention aid of polyethyleneimine was used to improve the loading capacity as well as prevent the aggregation of nanoparticles. Moreover, AuNR@AgNCs were modified with p-aminobenzenethiol to improve the affinity of SERS substrates to TNT via the formation of Meisenheimer complex. Owing to the unique structure and morphology of AuNR@AgNCs, the composite SERS substrate can detect trace TNT with a limit of detection of 8 × 10−12 g/L and the SERS enhancement factor is high up to 1.87 × 108.

Profiling DNA mutation patterns by SERS fingerprinting for supervised cancer classification

Profiling DNA mutation patterns for cancer classification plays an essential role in precision and personalized medicine. Conventional PCR-based mutation assay is limited by the extensive labour on target amplification. We herein create an amplification-free surface enhanced Raman spectroscopy (SERS) biochip which enables direct and simultaneous identification of multiple point mutations in tumor cells. Without pre-amplifying the target sequences, the SERS assay reads out the presence of cellular mutations through the interpretation of Raman fingerprints. The SERS sensor is integrated into a microfluidic chip, achieving one-step multiplex analysis within 40 min. Importantly, by combining SERS spectra encoding technique with supervised learning algorithm, a panel of nucleotide mixtures can be well distinguished according to their mutation profiles. We initially demonstrate an excellent levels of classification in samples from colorectal cancer and melanoma cell lines. For final clinical validation, the system performance is verified by classifying cancer patient samples, which shows an accuracy above 90%. Due to the simplicity and rapidness, the SERS biosensor is expected to become a promising tool for clinical point-of-care diagnosis towards precision medicine.

Silver nanoprisms/graphene oxide/silicon nanowires composites for R6G surface-enhanced Raman spectroscopy sensor

In this study, Silver nanoprisms/Graphene Oxide/Silicon nanowires (AgNPr/GO/SiNWs) nanocomposites have been fabricated for Surface-Enhanced Raman Spectroscopy (SERS) of Rhodamine 6G (R6G). The SiNWs have been synthesized using the metal-assisted chemical etching method. The surface morphologies of the SiNWs samples have been investigated using scanning electron microscopy. By varying the etching time from 5 to 30 min, the nanowire lengths have been tuned from 2 to 10 µm. While the average nanowire diameter remained unaffected (30-60 nm) with the increase in etching time, increments of nanowires length were found to alter the bundle morphology. The final SERS structure is obtained by depositing the GO layer followed by AgNPr. The obtained SERS sensor exhibited an enhanced efficiency as compared to AgNPr/SiNW matrix. The results demonstrate that a maximum efficiency factor of 6.1×1010 could be achieved with sensor fabricated with 30 min etched SiNWs.

Development and Application of Aptamer-Based Surface-Enhanced Raman Spectroscopy Sensors in Quantitative Analysis and Biotherapy.

Surface-enhanced Raman scattering (SERS) is one of the most special and important Raman techniques. An apparent Raman signal can be observed when the target molecules are absorbed onto the surface of the SERS substrates, especially on the “hot spots” of the substrates. Early research focused on exploring the highly active SERS substrates and their detection applications in label-free SERS technology. However, it is a great challenge to use these label-free SERS sensors for detecting hydrophobic or non-polar molecules, especially in complex systems or at low concentrations. Therefore, antibodies, aptamers, and antimicrobial peptides have been used to effectively improve the target selectivity and meet the analysis requirements. Among these selective elements, aptamers are easy to use for synthesis and modifications, and their stability, affinity and specificity are extremely good; they have been successfully used in a variety of testing areas. The combination of SERS detection technology and aptamer recognition ability not only improved the selection accuracy of target molecules, but also improved the sensitivity of the analysis. Variations of aptamer-based SERS sensors have been developed and have achieved satisfactory results in the analysis of small molecules, pathogenic microorganism, mycotoxins, tumor marker and other functional molecules, as well as in successful photothermal therapy of tumors. Herein, we present the latest advances of the aptamer-based SERS sensors, as well as the assembling sensing platforms and the strategies for signal amplification. Furthermore, the existing problems and potential trends of the aptamer-based SERS sensors are discussed.

Nanoforest-based SERS sensor fabricated using a maskless process for detecting chemical and pathogen

Nanoscale silicon forest-based surface enhanced Raman spectroscopy (SERS) sensor was fabricated using a simple maskless Bosch process method. Silicon nanoforest was further coated with gold and grafted with silver-plate nanoparticles. Fabricated SERS sensor was then utilized to detect 106 CFU/ml Escherichia coli (E. coli), achieving Raman signal enhancement of ~ 106. Furthermore, by detecting a mixture of R6G and E. coli, multiplexed detection was successfully demonstrated. A series of numerical simulation was performed to study the enhancement factor of the fabricated SERS sensor, matching the experimental results. Due to the simplicity of the fabrication process and its cost-effectiveness, this type of nanoforest SERS sensor is a promising cartridge-type device for a hand-held Raman spectrometer microsystem for both qualitative and quantitative detection of bacterial/viral pathogens in the field of food microbiology.

Amplification-free SERS analysis of DNA mutation in cancer cells with single-base sensitivity.

Accurate and sensitive identification of DNA mutations in tumor cells is critical to the diagnosis, prognosis and personalized therapy of cancer. Conventional polymerase chain reaction (PCR)-based methods are limited by the complicated amplification process. Herein, an amplification-free surface enhanced Raman spectroscopy (SERS) approach which directly detects point mutations in cancer cells has been proposed. A highly sensitive and uniform SERS substrate was fabricated using gold@silver core-shell nanorods, achieving an enhancement factor of 1.85 × 106. By combining the SERS-active nanosubstrate with molecular beacon probes, the limit of detection reached as low as 50 fM. To enable parallel analysis and automated operation, the SERS sensor was integrated into a microfluidic chip. This novel chip-based assay was able to differentiate between mutated and wild-type KRAS genes among a variety of other nucleic acids from cancer cells in 40 min. Owing to the simple operation and fast analysis, the SERS-based DNA assay chip could potentially provide insights into clinical cancer theranostics in an easy and inexpensive manner at the point of care.