Paper-based Surface-enhanced Raman Scattering Research Articles

Novel molecularly imprinted nanogel modified microfluidic paper-based SERS substrate for simultaneous detection of bisphenol A and bisphenol S traces in plastics

Paper-based surface-enhanced Raman scattering (SERS) optical nanoprobes provide ultrasensitive analyte detection; however, they lack selectivity, making them difficult to use in real-world sample analysis without a pretreatment process. This work describes the design of a microfluidic paper-based SERS substrate based on molecularly imprinted nanogels decorated with silver nanoparticles to simultaneously detect bisphenol A (BPA) and bisphenol S (BPS) traces in plastic toys and receipts. The synthesized nanogels have two characteristics that boost SERS performance: molecularly imprinted cavities that allow for selective adsorption and a wrinkled surface that creates uniformly distributed hot spots. Simple paper-based sensor devices were built as ‘drop and read’ SERS substrates with a separate reservoir to detect a single target, while advanced SERS platforms were designed as a microfluidic chip with two reservoirs connected by a channel for simultaneous detection of BPA and BPS. The SERS platform with a single reservoir showed outstanding analytical performance for the detection of BPA and BPS, with low detection limits of 0.38 pM and 0.37 pM, respectively. The microfluidic paper-based sensor allowed simultaneous and selective detection of BPA and BPS with detection limits estimated at 0.68 nM and 0.47 nM, respectively. The developed sensors are successfully applied to detect BPA and BPS in plastic products and receipts. Finally, the results obtained with our method showed greater sensitivity than those of commercially available ELISA kits, and the acquired values within the ELISA detection range were in excellent agreement.

Iodide Functionalized Paper-Based SERS Sensors for Improved Detection of Narcotics.

An inkjet-printed paper-based Surface-enhanced Raman scattering (SERS) sensor is a robust and versatile device that provides trace sensing capabilities for the detection and analysis of narcotics and drugs. Such sensors generally work well for analytes with good binding affinity towards the Au or Ag plasmonic nanoparticles (NPs) resident in the sensors. In this report, we show that iodide functionalization of the printed sensors helps to remove adsorbed contaminants from AuNP surfaces enabling superior performance with improved detection of narcotics such as fentanyl, heroin and cocaine by SERS. SERS signals are easily doubled with the iodide-functionalized sensors which also showed orders of magnitude improvement in detection limit. In this report, we show that a short (90 s) iodide treatment of the sensors significantly improved the detection of heroin. We propose that iodide functionalization be integrated into field detection kits through the solvent that wets paper-based sensor prior to swabbing for narcotics. Alternatively, we have also demonstrated that iodide functionalized sensors can be stored in ambient for up to 1 week and retain the improved performance towards heroin detection. This report will help to significantly improve the performance of paper-based sensors for field detection of narcotic drugs.

A Paper-Based Surface-Enhanced Raman Scattering (SERS) Biosensor for Label-Free Detection of Serum Bilirubin for Diagnosis of Jaundice

Jaundice continues to be a serious health concern and is among the leading causes of deaths during the first days of newborn babies’ lives. Serum bilirubin is currently being exploited in the clinic as a key biomarker for the diagnosis and management of neonatal jaundice. The commonly used methods for serum bilirubin determination in clinical settings are direct spectroscopic measurement and the diazo reaction method. These methods have drawbacks such as low sensitivity, matrix interference, poor stability, high-cost, professional training, less specificity and tedious sample preparation. Thus, it is very urgent to develop a rapid and economical route for sensitive and specific detection of free bilirubin directly in human serum.Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for biosensing applications with high sensitivity, molecular specificity, powerful multiplex detection capability, and excellent photostability. This talk will present our recent study on the development of a paper-based SERS biosensor for label-free detection of bilirubin in serum. This biosensor comprises multifunctional graphene oxide-gold nanostar (GO-GNS) hybrids decorated on the filter paper. This biosensor combines the enrichment for serum bilirubin and plasmonic enhancement for Raman signals of bilirubin for boosting the label-free detection sensitivity directly in blood serum without the need for additional sample preparation. Our results demonstrated the excellent detection performance for detection of bilirubin directly in serum in a label-free manner, and the detection results were compared with the commercial diazo reaction method, which justifies the clinical effectiveness and suitability of the present paper-based SERS biosensor. We believe that the present paper-based SERS biosensor has great potential for clinical translation in accurate diagnosis of jaundice and other related diseases. Reference: Xiang Pan, Linhu Li, Hangduo Lin, Jiayi Tan, Haitao Wang, Mengling Liao, Caiju Chen, Beibei Shan, Yingfan Chen, Ming Li, A graphene oxide-gold nanostar hybrid based-paper biosensor for label-free SERS detection of serum bilirubin for diagnosis of jaundice, Biosensors and Bioelectronics, 2019, 145, 111713.

Inkjet Printing of Ag and Polystyrene Nanoparticle Emulsions for the One-Step Fabrication of Hydrophobic Paper-Based Surface-Enhanced Raman Scattering Substrates

Inkjet Printing of Ag and Polystyrene Nanoparticle Emulsions for the One-Step Fabrication of Hydrophobic Paper-Based Surface-Enhanced Raman Scattering Substrates

Optimization and Characterization of Paper-based SERS Substrates for Detection of Melamine

A flexible low-cost paper-based surface enhanced Raman scattering (SERS) substrate was successfully manufactured by a direct chemical reduction of silver nanoparticles (AgNPs) onto a common commercially available filter paper. Characterization of fabricated paper-based SERS substrate and the influences of the silver nitrate concentration, type of paper on SERS signal were systematically investigated. In order to fabricate SERS substrates with the highest quality, a suitable one from four different types of filter papers was chosen. The prepared SERS substrates have capability for detecting food toxic chemicals. The test of detecting melamine in aqueous solution was successfully demonstrated with the limit of detection for melamine is 10-7M.

PCR-coupled Paper-based Surface-enhanced Raman Scattering (SERS) Sensor for Rapid and Sensitive Detection of Respiratory Bacterial DNA

A paper-based surface-enhanced Raman scattering (SERS) substrate composed of silver-nanowires (AgNWs) was coupled with polymerase chain reaction (PCR) for rapid and sensitive determination of respiratory bacterial DNA. EvaGreen dye, which is a DNA intercalating molecule, was introduced to the low-cycled PCR product, and the difference in dye intercalation in the DNA structure was quantified by Raman spectroscopy to verify the presence of a target gene. Mycoplasma pneumoniae (M. Pne), was selected as a target for the sensing demonstration. At various gene concentrations and amplification cycles, detection capability of fluorescence-based real-time PCR (RT-PCR) and the PCR-coupled SERS method were compared to develop a DNA detection system capable of low-cycle amplification and sensitive DNA sensing. After 10 cycles, the PCR-coupled SERS method showed enhanced detection capability with a DNA detection limit of 3.12 pg/μL. Then, the SERS substrate was prepared as a rapid kit that included a test line and negative and positive control lines. Target DNA after 10 cycles of amplification was successfully discriminated compared to non-target DNA and it was statistically relevant. The developed system is expected to be used as a detection method for various bacteria and viruses, and also be integrated with diverse POC diagnostic systems.

A Paper-Based Surface-Enhanced Raman Scattering (SERS) Biosensor for Label-Free Detection of Serum Bilirubin for Diagnosis of Jaundice

Jaundice continues to be a serious health concern and is among the leading causes of deaths during the first days of newborn babies’ lives. Serum bilirubin is currently being exploited in the clinic as a key biomarker for the diagnosis and management of neonatal jaundice. The commonly used methods for serum bilirubin determination in clinical settings are direct spectroscopic measurement and the diazo reaction method. These methods have drawbacks such as low sensitivity, matrix interference, poor stability, high-cost, professional training, less specificity and tedious sample preparation. Thus, it is very urgent to develop a rapid and economical route for sensitive and specific detection of free bilirubin directly in human serum.Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for biosensing applications with high sensitivity, molecular specificity, powerful multiplex detection capability, and excellent photostability. This talk will present our recent study on the development of a paper-based SERS biosensor for label-free detection of bilirubin in serum. This biosensor comprises multifunctional graphene oxide-gold nanostar (GO-GNS) hybrids decorated on the filter paper. This biosensor combines the enrichment for serum bilirubin and plasmonic enhancement for Raman signals of bilirubin for boosting the label-free detection sensitivity directly in blood serum without the need for additional sample preparation. Our results demonstrated the excellent detection performance for detection of bilirubin directly in serum in a label-free manner, and the detection results were compared with the commercial diazo reaction method, which justifies the clinical effectiveness and suitability of the present paper-based SERS biosensor. We believe that the present paper-based SERS biosensor has great potential for clinical translation in accurate diagnosis of jaundice and other related diseases.

Paper-based sandwich type SERS sensor based on silver nanoparticles and biomimetic recognizer

A paper-based surface enhanced Raman scattering (SERS) sensor with synergistic enhancement strategy for selective detection of tartrazine in food products has been established in this work. For economic and mass production purposes, paper substrates were firstly installed with a silver layer to endow the paper with electroconductibility and dense plasmonic hotspots. A biomimetic recognizer (BR) membrane was attached upon the Ag paper as specific identification device, and a layer of high-density of silver nanoparticles (AgNPs) was decorated on the surface of Ag/BR paper through in-situ growth method to form a sandwich structure. Since the double layer of Ag/AgNPs demonstrated excellent local plasma resonance effect, combined with the identification function of BR, it made the paper SERS sensor emerge incredible Raman synergistic enhancement response on tartrazine molecules embraced the plasma nanoparticles. Thus, the synergistically enhanced Ag/BR/AgNPs paper SERS sensor was achieved and applied in on-site test of tartrazine in Children's snacks. The linear range (0.3∼10 μg mL−1) and the limit of detection (0.1138 μg mL−1) of the SERS paper strip could be applied as a screening or occupational cut-off of tartrazine (100 μg mL−1) for reference. In addition, the proposed paper sensor can be a potential candidate for multicomponent screening and is suitable for mass production and promotion.

Paper-Based SERS Sensing Platform Based on 3D Silver Dendrites and Molecularly Imprinted Identifier Sandwich Hybrid for Neonicotinoid Quantification.

Real-time monitoring of neonicotinoid pesticide residues is of great significance for food security and sustainable development of the ecological environment. Herein, a paper-based surface-enhanced Raman scattering (SERS) amplified approach was proposed by virtue of multilayered plasmonic coupling amplification. The unique plasmonic SERS multilayer was constructed using three-dimensional (3D) silver dendrite (SD)/electropolymerized molecular identifier (EMI)/silver nanoparticle (AgNP) sandwich hybrids with multiple hotspots and a strong electromagnetic field in nanogaps. Dendritelike 3D silver materials with remarkably high accessible surface areas and the lightning rod effect constituted the first-order enhancement of paper-based sensors. Molecular identifiers coated upon an SD layer as the interlayer were used for target capture and enrichment. Subsequently, AgNPs featuring rough surface and local plasma resonance decorated as the top layer formed the secondary enhancement of the amplification strategy. As the most brilliant part, dendritelike 3D silver coupled with AgNPs has established double Ag layers to accomplish a multistage enhancement of SERS signals based on the superposition of their electromagnetic fields. Owning to the distinctive design of the multiple coupling amplification strategy, the fabricated SERS paper chips demonstrated impressive specificity and ultrahigh sensitivity in the detection of imidacloprid (IMI), with a detection limit as low as 0.02811 ng mL-1. More importantly, the multiple SERS enhancement paper chip holds great potential for automated screening of a variety of contaminants.

Hydrophobic Paper-Based SERS Sensor Using Gold Nanoparticles Arranged on Graphene Oxide Flakes.

Paper-based surface-enhanced Raman scattering (SERS) sensors have garnered much attention in the past decade owing to their ubiquity, ease of fabrication, and environmentally friendly substrate. The main drawbacks of a paper substrate for a SERS sensor are its high porosity, inherent hygroscopic nature, and hydrophilic surface property, which reduce the sensitivity and reproducibility of the SERS sensor. Here, we propose a simple, quick, convenient, and economical method for hydrophilic to hydrophobic surface modification of paper, while enhancing its mechanical and moisture-resistant properties. The hydrophobic paper (h-paper) was obtained by spin-coating diluted polydimethylsiloxane (PDMS) solution onto the filter paper, resulting in h-paper with an increased contact angle of up to ≈130°. To complete the h-paper-based SERS substrate, gold nanoparticles arranged on graphene oxide (AuNPs@GO) were synthesized using UV photoreduction, followed by drop-casting of AuNPs@GO solution on the h-paper substrate. The enhancement of the SERS signal was then assessed by attaching a rhodamine 6G (R6G) molecule as a Raman probe material to the h-paper-based SERS substrate. The limit of detection was 10 nM with an R2 of 0.966. The presented SERS sensor was also tested to detect a thiram at the micromolar level. We expect that our proposed AuNPs@GO/h-paper-based SERS sensor could be applied to point-of-care diagnostics applications in daily life and in spacecraft.

A facile low-cost paper-based SERS substrate for label-free molecular detection

We introduce a facile and low-cost method for fabricating gold nanostructures on cellulose filter paper (CFP) to prepare a paper-based surface-enhanced Raman scattering (SERS) sensor for label-free molecular detection. Polymerized dopamine (PD) was used as an adhesive layer on the CFP and simultaneously functioned as a reducing agent for gold nanoparticle (AuNP) nucleation. The size of the AuNPs was dependent on the pH of the gold precursor solution, and nanoparticles with an average size of 102 nm were formed on the PD-coated CFP at a pH 3, exhibiting high SERS activity. Finite-difference time-domain (FDTD) simulations of the electromagnetic field enhancement of AuNPs with different sizes and interparticle distances were performed to identify the origin of the SERS effect. The developed paper-based SERS substrate showed uniform and excellent molecular sensitivity with a limit of detection (LOD) of 10−7 M for methylene blue, as measured by a portable Raman spectrometer. Furthermore, as a field application test, surfaces of apples were pretreated with diquat (DQ) and paraquat (PQ) pesticides, which were then detected down to a concentration of 1 ppm after simple attachment of the sensor on the apple peels and performing a SERS measurement. The developed paper-based SERS sensor is expected to be applicable as a label-free sensor for a variety of chemical and biological molecules.

A simple paper-based surface enhanced Raman scattering (SERS) platform and magnetic separation for cancer screening

Early and precise diagnosis of cancer is critical for a better prognosis. Here, we describe a simple and cost-effective plasmonic paper as a surface enhanced Raman scattering (SERS) substrate in combination with magnetic separation for cancer screening. The plasmonic paper was fabricated by immersing plain filter paper into gold nanorod solution and the SERS property of the paper was evaluated using 4-mercaptobenzoic acid (4-MBA) and rhodamine 6 G (R6 G), which showed an enhancement factor (EF) in the range of 106–108. HT-29, a colorectal cancer cell line that highly expresses epithelial cell adhesion molecule (EpCAM), served as the target cells; non-EpCAM-expressing cells, namely fibroblasts and red blood cells (RBCs), were used as negative controls. Intrinsic SERS spectra of the target and control cells showed distinctive patterns on the plasmonic paper due to differences in their structure and components. A combination of principal component analysis (PCA) and k-nearest-neighbor algorithm (k-NN) was employed to analyze and distinguish the acquired HT-29 and fibroblast SERS spectra, demonstrating a diagnostic sensitivity and specificity of 84.8% and 82.6%, respectively, whereas the differentiation between HT-29 and RBCs SERS spectra showed a sensitivity and specificity of 96.4% and 100%, respectively. The magnetic separation was applied to capture the target cells from cell mixtures followed by PCA and k-NN analysis. The identification of the captured cells as cancerous cells from the HT-29 and fibroblast mixture indicated an accuracy of 83.7%, while that from a mixture of HT-29 and RBCs was 98.2%. Thus, the simple paper-based SERS substrate with the assistance of magnetic enrichment and multivariate analysis offers a potent new platform for cancer cell detection and screening.

纸质表面增强拉曼散射基底的制备及其应用进展

纸质表面增强拉曼散射基底的制备及其应用进展

Paper-Based Surface-Enhanced Raman Scattering Lateral Flow Strip for Detection of Neuron-Specific Enolase in Blood Plasma.

An inexpensive and disposable paper-based lateral flow strip (PLFS) has been developed as an immunoassay, in which surface-enhanced Raman scattering (SERS) is utilized for sensing signal transduction. The Au nanostar@Raman Reporter@silica sandwich nanoparticles are developed as the SERS probes, which is the key to the high sensitivity of the device. Compared with a colorimetric PLFS, the SERS-PLFS exhibits superior performance in terms of sensitivity and limit of detection (LOD) in a blood plasma-containing sample matrix. In addition, the SERS-PLFS has been successfully used for detection of neuron-specific enolase (NSE), a traumatic brain injury (TBI) protein biomarker, in diluted blood plasma samples, achieving a LOD of 0.86 ng/mL. Moreover, the SERS-PLFS was successfully employed to measure the NSE level in clinical blood plasma samples taken from deidentified TBI patients. This work demonstrates that the SERS-PLFS has great potential in assisting screening of TBI patients in the point-of-care setting.

A Paper-Based Surface-Enhanced Raman Scattering Test Strip for Protein Biomarker Detection

Paper-based lateral flow strips (PLFS) have received increasing attention as point-of-care (POC) tools due to their low cost and simplicity to use. However, PLFS usually suffer from poor sensitivity and serious interference from their sample matrix when they are used with blood plasma containing samples. In our current study, surface-enhanced Raman scattering (SERS) was integrated as the signal transducer into PLFS for protein biomarker detection in blood plasma. Compared with the traditional colorimetric PLFS, the SERS PLFS exhibits advantages in terms of sensitivity and limit of detection (LOD) in a blood plasma sample matrix. These advantages are attributed to the wavelengths of both the excitation light and the Raman scattering signals being able to be tuned into the near-infrared biological window. Herein, our developed SERS PLFS has been successfully demonstrated for detection of neuron-specific enolase (NSE) in diluted blood plasma samples with a LOD of 1 ng/ml. Moreover, these SERS based test strips are in expensive, fast (30 min) and simple to be operated, holding a great potential in assisting screening of traumatic brain injury (TBI) patients in a point-of-care setting.