Surface-enhanced Raman Scattering Chip Research Articles

Hydrogel SERS chip with strong localized surface plasmon resonance for sensitive and rapid detection of T-2 toxin

T-2 toxin is one of the naturally dangerous food contaminants, which is harmful to people and animals. Because of its strong toxicity and wide distribution, it is vital to develop a rapid and effective method for the detection of T-2 toxin. Herein, an excellent hydrogel surface-enhanced Raman scattering (SERS) chip is constructed for developing a novel SERS sensor to detect T-2 toxin using a portable Raman spectrometer. The SERS chip is prepared by in-situ Ca2+-mediated assembly of silver nanoparticles (AgNPs) in PVA solution, followed by a physical crosslinking possess. The assembled AgNPs produces a strong localized surface plasmon resonance (LSPR) at around 532 nm, which enables the high activity of SERS chip under the irradiation of 532 nm laser. Additionally, the unique structure of hydrogel makes the obtained chip show excellent reliability and anti-interference ability in detection. As a result, the developed SERS sensor shows many obvious advantageous including free of complex sample pretreatment (only a simple extraction), fast response (5 min), low limit of detection (0.41 ppb), wide detection range (1–10000 ppb), good recoveries (90.26–101.81 %) and relative standard deviations (2.8–6.7 %). Therefore, this SERS sensor provides a promising choice for rapid scanning and sensitive detection of trace T-2 toxin in complex matrices.

(Invited) Resonator and SERS Sensing in the Field of Drug Delivery

Introduction Our research center of excellence IDUN combines research in nanosensors/centrifugal microfluidics and microfabricated devices for oral drug delivery. This allows us to explore the synergy between sensor development and search for new pharmaceutical delivery tools and materials. Our developed nanosensors get access to unique polymers and biomolecules and are able to characterize, among others, small volumes of materials and molecules, which are today not possible to analyze by any standard technologies. We will show examples of recent findings and results within drug/polymer characterization (1) and process monitoring (2) using nanomechanical sensors. Also, new applications within therapeutic drug monitoring using Surface Enhanced Raman Scattering (SERS) will be presented as well as sensor integration with centrifugal microfluidics platforms. Resonators By monitoring the resonance frequency shift of micrometer sized strings or cantilevers coated with thin layers of polymers, it is possible to monitor phase transitions using only ng of material. We have been able to observe beta relaxation of polymers (3) and drugs (2), see figure 1. These systems also allowed us to monitor degradation of biomaterials used in the fabrication of the microcontainers (4). Also, strings are inherently sensitive to temperature changes (5). The resonant frequency detunes as a function of temperature and temperature changes down to 10-5 °C can be detected. The effect has been used to perform photothermal IR spectra on samples deposited on resonating strings and resonating filters. This has been used to for example study the amorphous and crystalline forms of indomethacin (1). As an alternative to cleanroom fabricated resonators we have used single drug and collagen particles as micro mechanical resonators, thereby eliminating the need for cleanroom processing. This method additionally makes it possible to study the behavior of single crystals, which would otherwise be extremely difficult/impossible. This method has, among others, allowed us to study new phenomena in the hydration/dehydration of drugs (6). Centrifugal microfluidics The optics and mechanics from a DVD player can be used to realize compact and sensitive sensor systems. By rotating a polymer disc with integrated microfluidic channels it is possible to manipulate liquid samples such as blood – performing crucial operations like separation, valving and mixing. We integrate sensor elements such as cantilevers, nanoparticles, resonating strings and SERS substrates with centrifugal microfluidics (7). The sensors are read out by a DVD pick-up head, which can perform transmission/absorption measurements and can detect nm deflections. Also, electrodes and spectrometers are integrated on a disc platform, facilitating electrochemical/Raman measurements. Our nanopillar SERS substrate can be used for sample filtration and separation. Here the nanopillars function similarly to a filter paper in chromatography and can be used to distinguish e.g. different components in a urine sample as well as drug residuals. A SERS chip is placed in a centrifugal microfluidics platform, whereby the sample can be initially centrifuged. Subsequently half the SERS chip is exposed to the centrifuged liquid. Hereby, liquid can travel up the chip by the so-called wicking effect, and depending on affinity of molecules to the surface, different molecules will travel different lengths. Hereby, a separation is secured and the different molecules are read-out as bands on the SERS chip. Acknowledgements This research has received funding from the ERC grant agreement n° 320535 and from the Center of Excellence ’IDUN’ granted by Danish National Research Foundation, DNRF122/the Velux Foundations.

Flexible Surface-Enhanced Raman Scattering Chip: A Universal Platform for Real-Time Interfacial Molecular Analysis with Femtomolar Sensitivity.

We propose and demonstrate a flexible surface-enhanced Raman scattering (SERS) chip as a versatile platform for femtomolar detection and real-time interfacial molecule analysis. The flexible SERS chip is composed of a flexible and transparent membrane and embedded plasmonic dimers with ultrahigh particle density and ultrasmall dimer gap. The chip enables rapid identification for residuals on solid substrates with irregular surfaces or dissolved analytes in aqueous solution. The sensitivity for liquid-state measurement is down to 0.06 molecule per dimers for 10-14 mol·L-1 Rhodamine 6G molecule without molecule enrichment. Strong signal fluctuation and blinking are observed at this concentration, indicating that the detection limit is close to the single-molecule level. Meanwhile, the homogeneous liquid environment facilities accurate SERS quantification of analytes with a wide dynamic range. The synergy of flexibility and liquid-state measurement opens up avenues for the real-time study of chemical reactions. The reduction from p-nitrothiophenol (PNTP) to p-aminothiophenol (PATP) in the absence of the chemical reducing agents is observed at liquid interfaces by in situ SERS measurements, and the plasmon-induced hot electron is demonstrated to drive the catalytic reaction. We believe this robust and feasible approach is promising in extending the SERS technique as a general method for identifying interfacial molecular traces, tracking the evolution of heterogeneous reactions, elucidating the reaction mechanisms, and evaluating the environmental effects such as pH value and salty ions in SERS.

Ratiometric SERS biosensor for sensitive and reproducible detection of microRNA based on mismatched catalytic hairpin assembly

MicroRNAs (miRNAs) serve as significant regulators in a variety of diseases and have been emerging as a class of promising biomarkers for early cancer diagnosis. Herein, an enzyme-free surface-enhanced Raman scattering (SERS) platform was proposed for sensitive and reliable detection of target miRNA-21 using a corrective internal standard (IS)-based ratiometric SERS probe coupled with mismatched catalytic hairpin assembly (CHA) amplification. The 4-aminothiophenol (4-ATP) was used as IS molecule and modified on the surface of silver nanoparticles decorated silicon wafer. In principle, the presence of miRNA-21 could cyclically trigger the allosteric effects of mismatched CHA amplification and the 3′-R6G labeled hairpin probe 1 (H1) was opened. Then, the hairpin probe 2 (H2) hybridized with H1 to form H1–H2 complex and the released miRNA-21 was free to participate in the next cycle of CHA reaction. Meanwhile, the H1–H2 complex could hybridize with the capture DNA on the SERS chip, making the Raman tag of R6G close to the surface of SERS substrate, and the intensity of SERS signal from R6G labels increase while that from 4-ATP remain relatively unchanged. Benefiting from outstanding performances of the ratiometric SERS strategy and enzyme-free CHA amplification system, this platform exhibits sensitivity toward miRNA-21 with a limit of detection of 3.5 fM and a broad dynamic range from 10 fM to 100 nM. More importantly, this proposed method presents an excellent reliable SERS analysis with the correction of IS. The developed strategy holds a potential alternative tool for miRNA detection in biomedical research and early clinical diagnosis.

Detection of Pesticide Residues Using Nano-SERS Chip and a Smartphone-Based Raman Sensor

Nowadays, detection of pesticide residues is generally conducted in the laboratory using large-scale equipment such as liquid chromatography mass spectrometry, etc. These detection methods usually require a complicated pre-treatments and professional operators, which are time-consuming and expensive. Surface-enhanced Raman scattering (SERS) technology makes trace detection of pesticide residues implementable, but currently the devices for SERS on the market are all large-scale and rapid detection of pesticide residues has not been achieved yet. In this paper, a novel SERS system integrated with a cellphone is designed for the detection of pesticide residues. In the current system, the SERS chip is inserted directly onto the, and measurement of pesticide residues can be conducted by one-click through the cellphone application. We achieved successfully detection of 12 kinds of pesticides with characteristic Raman spectra and the limit of detection was less than 10 ppm, which makes rapid and on-site detection of pesticide residues feasible in future point of care test applications.

Setting Up a Surface-Enhanced Raman Scattering Database for Artificial-Intelligence-Based Label-Free Discrimination of Tumor Suppressor Genes.

The quality of input data in deep learning is tightly associated with the ultimate performance of the machine learner. Taking advantage of the unique merits of surface-enhanced Raman scattering (SERS) methodology in the collection and construction of a database (e.g., abundant intrinsic fingerprint information, noninvasive data acquisition process, strong anti-interfering ability, etc.), herein we set up a SERS-based database of deoxyribonucleic acid (DNA), suitable for artificial intelligence (AI)-based sensing applications. The database is collected and analyzed by silver nanoparticles (Ag NPs)-decorated silicon wafer (Ag NPs@Si) SERS chip, followed by training with a deep neural network (DNN). As proof-of-concept applications, three kinds of representative tumor suppressor genes, i.e., p16, p21, and p53 fragments, are readily discriminated in a label-free manner. Prominent and reproducible SERS spectra of these DNA molecules are collected and employed as input data for DNN learning and training, which enables selective discrimination of DNA target(s). The accuracy rate for the recognition of specific DNA target reached 90.28%.

Sensitive and Selective Detection of Mercury Ions in Aqueous Media Using an Oligonucleotide-functionalized Nanosensor and SERS Chip.

A surface-enhanced Raman scattering (SERS) platform for the selective trace analysis of Hg2+ ions was reported, based on poly-thymine (T) aptamer/2-naphthalenethiol (2-NT)-modified gold nanoparticles (AuNPs), which was an oligonucleotide-functionalized nanosensor and SERS chip. 2-NT was used as a Raman reporter, and T aptamer could form a T-Hg2+-T structure with Hg2+ ions making an SERS nanosensor absorbed to the SERS chip. The optimum concentrations of DNA and 2-NT were obtained. An average of 960 DNA molecules attached to each AuNP were measured. The limit of detection (LOD) was 1.0 ppt (1.0 × 10-12 g/mL), which is far below the limit of 10.0 ppb for drinking water, stipulated by the World Health Organization. The sensor has the advantages of low detection cost, a simple sample pretreatment, a green solution and reducing false positives. Furthermore, the nanosensor was used for the determination of trace Hg2+ in the water of a lake; a reliable result was obtained accurately.

A nano‐plasmonic chip for simultaneous sensing with dual‐resonance surface‐enhanced Raman scattering and localized surface plasmon resonance

AbstractA dual‐resonance surface‐enhanced Raman scattering (SERS) chip which also serves as a localized surface plasmon resonance (LSPR) refractive index sensor is proposed. The dual‐resonance SERS chip can simultaneously enhance excitation and Stokes lines for Raman signals detection in a broad wavelength region with virtually no limitation. Thus, it is especially useful for Raman detection at long wave numbers and hyper Raman. The great performance of this chip relies on the highly independent tunability of the two localized plasmonic resonances from the optical to the near‐infrared region and the strict “hot spot” match in space for both resonant wavelengths. Furthermore, Raman signals of poly‐methyl‐methacrylate (PMMA) from 500 cm−1 to 3300 cm−1 are measured in the experiments and an obvious superiority can be seen compared to a single‐resonance SERS chip. In an addition, by using the subradiant magnetic dipole resonance, the LSPR refractive sensor gives a high sensitivity of 577 nm/RIU and high figure of merit (FoM) of 14.2. The experimental results are consistent with the simulated results. This dual‐functional sensing chip opens a route for dual‐modality detection of the concentration of some specific molecules.

Surface-Enhanced Raman Scattering Chip for Femtomolar Detection of Mercuric Ion (II) by Ligand Exchange

The chemical sensing for the convenient detection of mercuric ion (II) (Hg(2+)) have been widely explored with the use of various sensing materials and techniques. It still remains a challenge to achieve ultrasensitive but simple, rapid, and inexpensive detection to metal ions. Here we report a surface-enhanced Raman scattering (SERS) chip for the femtomolar (fM) detection of Hg(2+) by employing silver-coated gold nanoparticles (Au@Ag NPs) together with an organic ligand. 4,4'-Dipyridyl (Dpy) can control the aggregation of Au@Ag NPs via its dual interacting sites to Ag nanoshells to generate strong Raman hot spots and SERS readouts. However, the presence of Hg(2+) can inhibit the aggregation of Au@Ag NPs by the coordination with Dpy, and as a result the SERS signals of Dpy are quenched. On the basis of these findings, a SERS chip has been fabricated by the assembly of Au@Ag NPs on a piece of silicon wafer and the further modification with Dpy. The exchange of Dpy from the chip into the aqueous Hg(2+) droplet results in the quenching of Raman signals of Dpy, responding to 10 fM Hg(2+) that is about 6 orders of magnitude lower than the limit defined by the U.S. Environmental Protection Agency in drinkable water. Each test using the SERS chip only needs a droplet of 20 μL sample and is accomplished within ∼4 min. The SERS chip has also been applied to the quantification of Hg(2+) in milk, juice, and lake water.