Surface-enhanced Raman spectroscopy (SERS) is an emerging analytical technique with high speed and sensitivity, despite some shortcomings. Combined with other techniques can overcome these limitations and enhance the capability for detection and characterization with SERS, and has been successfully in many recent studies. Various SERS combined techniques are systematically summarized in this review for the first time. SERS can be combined with diverse techniques, such as chemical separation, biological capturing, colorimetry, microfluidic devices, and labeling techniques, to enhance detection capabilities. Moreover, combinations of SERS and other chemical analytical techniques such as mass spectroscopy, nuclear magnetic resonance, Infrared spectroscopy, and X-ray photoelectron spectroscopy, can enable more precise characterization. The theories and applications of these SERS combined techniques as well as their pros and cons are compared, and further perspectives are proposed. This review provides new insights into advances in SERS combined techniques and their use in real-life studies.

Surface-enhanced Raman spectroscopy (SERS) combined techniques for high-performance detection and characterization

In recent years, bioanalytical surface-enhanced Raman spectroscopy (SERS) has blossomed into a fast-growing research area. Owing to its high sensitivity and outstanding multiplexing ability, SERS is an effective analytical technique that has excellent potential in bioanalysis and diagnosis, as demonstrated by its increasing applications in vivo. SERS allows the rapid detection of molecular species based on direct and indirect strategies. Because it benefits from the tunable surface properties of nanostructures, it finds a broad range of applications with clinical relevance, such as biological sensing, drug delivery and live cell imaging assays. Of particular interest are early-stage-cancer detection and the fast detection of pathogens. Here, we present a comprehensive survey of SERS-based assays, from basic considerations to bioanalytical applications. Our main focus is on SERS-based pathogen detection methods as point-of-care solutions for early bacterial infection detection and chronic disease diagnosis. Additionally, various promising in vivo applications of SERS are surveyed. Furthermore, we provide a brief outlook of recent endeavours and we discuss future prospects and limitations for SERS, as a reliable approach for rapid and sensitive bioanalysis and diagnosis.

/pdf/surface-enhanced-raman-spectroscopy-for-bioanalysis-and-5fesoo09gf.pdf

Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique, which allows quantitative detection of chemical species with molecular specificity and single-molecule sensitivity. These useful properties can be further combined with portable Raman spectrometers which allow SERS to be potentially employed at the point-of-care. As a result, SERS has found a wide range of potential applications in both real-life chemical analysis and fundamental mechanistic studies. Despite these advantages, true applications of SERS have been limited due to its high cost, which arises mainly from the fact that SERS relies on expensive single-use Ag/Au enhancing substrates suitable only for the analysis of pure samples. A viable approach to address this issue is to develop multifunctional SERS substrates, which in addition to providing Raman signal enhancement, is armed with other practical functionalities that simplifies the analysis and/or allows the substrate to be regenerated for repeated use. This review gives an account of the recent progress in the fabrication of multi-functional SERS substrates, namely flexible, separation-enhancement-in-one, calibration-enhancement-in-one and regeneration-enhancement-in-one substrates. Specific focus is placed on summarizing and discussing the most widely used strategies to incorporate each type of functionality and their respective advantages and drawbacks. Finally, we present our perspectives on the future challenges and potential opportunities in the development of smart multifunctional SERS sensors for achieving sustainable and wide-spread application of SERS.

/pdf/towards-practical-and-sustainable-sers-a-review-of-recent-7al68aiuj1.pdf

Towards practical and sustainable SERS: a review of recent developments in the construction of multifunctional enhancing substrates

Surface-enhanced Raman spectroscopy (SERS) is garnering considerable attention for the swift diagnosis of pathogens and abnormal biological status, that is, cancers. In this work, a simple, fast and inexpensive optical sensing platform is developed by the design of SERS sampling and data analysis. The pretreatment of spectral measurement employed gold nanoparticle colloid mixing with the serum from patients with colorectal cancer (CRC). The droplet of particle-serum mixture formed coffee-ring-like region at the rim, providing strong and stable SERS profiles. The obtained spectra from cancer patients and healthy volunteers were analyzed by unsupervised principal component analysis (PCA) and supervised machine learning model, such as support-vector machine (SVM), respectively. The results demonstrate that the SVM model provides the superior performance in the classification of CRC diagnosis compared with PCA. In addition, the values of carcinoembryonic antigen from the blood samples were compiled with the corresponding SERS spectra for SVM calculation, yielding improved prediction results.

Label-free diagnosis for colorectal cancer through coffee ring-assisted surface-enhanced Raman spectroscopy on blood serum.

Liquid-liquid extraction-assisted SERS-based determination of sulfamethoxazole in spiked human urine.

Antipsychotic drug poisoning monitoring of clozapine in urine by using coffee ring effect based surface-enhanced Raman spectroscopy.

Thin-layer chromatography (TLC) coupled with surface-enhanced Raman spectroscopy (SERS) has gained tremendous popularity in the study of various complex systems. However, the detection of hydrophobic analytes is difficult, and the specificity still needs to be improved. In this study, a SERS-active non-aqueous silver sol which could activate the analytes to produce rich and stable spectral features was rapidly synthesized. Then, the optimized silver nanoparticles (AgNPs)-DMF sol was employed for TLC-SERS detection of hydrophobic (and also hydrophilic) analytes. SERS performance of this sol was superior to that of traditional Lee–Meisel AgNPs due to its high specificity, acceptable stability, and wide applicability. The non-aqueous AgNPs would be suitable for the TLC-SERS method, which shows great promise for applications in food safety assurance, environmental monitoring, medical diagnoses, and many other fields.

/pdf/a-widely-applicable-silver-sol-for-tlc-detection-with-rich-19j36832pm.pdf

A Widely Applicable Silver Sol for TLC Detection with Rich and Stable SERS Features

Thin layer chromatography coupled with surface enhanced Raman spectroscopy (TLC-SERS) has received great development but still suffers from the problem of detecting hydrophobic analytes. A relatively universal silver colloid, which is applicable for both hydrophilic and hydrophobic analytes, has been synthesized to solve this problem. However, it is difficult to obtain a fast response for reaching the maximum SERS intensity. Herein, we further optimized the preparation process of the above universal silver colloid, namely silver nanoparticles synthesized in N,N-dimethylformamide (AgNPs-DMF), and studied their surface enhanced Raman spectroscopy (SERS) performance on TLC plates. Here, the SERS performance of the silver colloids prepared with different mass ratios (AgNO3/PVP, m/m) was compared and we found that DMF 2 : 1 silver colloid gave the largest enhancement ability. In addition, it was also found that DMF 2 : 1 silver colloid could be stored for 90 days without significant intensity attenuation. Moreover, practical application of this novel DMF 2 : 1 colloid combined with the TLC-SERS method to analyze real botanical dietary supplement (BDS) samples claiming to have lipid-lowering or antitussive and antiasthmatic effects was successfully carried out. Results showed that the application of this newly synthesized fast response and highly stable non-aqueous sol using the TLC-SERS technique would have bright prospects for the rapid detection of large amounts of samples on site.

A fast response TLC-SERS substrate for on-site detection of hydrophilic and hydrophobic adulterants in botanical dietary supplements

Adulteration of herbal dietary supplements (HDSs) with undeclared synthetic drugs is a world-wide problem that poses a serious threat to human health. Methods ensuring the quality and safety of these supplements need to be developed. Herein, for the first time, highly sensitive thin layer chromatography combined with surface enhanced Raman spectroscopy (TLC-SERS) for the high efficiency screening of HDSs adulterated with up to nine lipid-lowering agents (LLAs) was put forward. After the optimization of two types of thin layer plates and several mobile phases, the nine different LLAs were well separated from the complex HDS matrix. Then, with the relatively universal SERS active silver colloids, all nine analytes presented abundant specific features for identification. This method was highly sensitive which enabled successful detection when the adulteration amount was as low as 0.002% (w/w). Moreover, practical applications of the established coupled method were demonstrated with the rapid analysis of twelve real HDS samples, one of which was found to be adulterated with simvastatin (SIM). The identification results were then verified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) analysis. The proposed method is simple and rapid, and has good prospects for high efficiency screening and sensitive analysis of multiple adulterants in HDSs.

High efficiency screening of nine lipid-lowering adulterants in herbal dietary supplements using thin layer chromatography coupled with surface enhanced Raman spectroscopy

Yongfang Yuan

Papers

Antipsychotic drug poisoning monitoring of clozapine in urine by using coffee ring effect based surface-enhanced Raman spectroscopy.

A Widely Applicable Silver Sol for TLC Detection with Rich and Stable SERS Features

A fast response TLC-SERS substrate for on-site detection of hydrophilic and hydrophobic adulterants in botanical dietary supplements

High efficiency screening of nine lipid-lowering adulterants in herbal dietary supplements using thin layer chromatography coupled with surface enhanced Raman spectroscopy