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Cervical cancer is a common cause of cancer-related death in women worldwide, and quantitative detection of serum tumor markers has practical implications for diagnosing cervical cancer. In this study, a novel surface-enhanced Raman scattering (SERS)-based immunosensor for the hypersensitive simultaneous detection of survivin and osteopontin (OPN) in cervical cancer serum was proposed, which was composed of the AuNPs@SiO2 microspheres (Au@SiO2) array immunosubstrate and Au-Ag nanoshells (Au-AgNSs) immunoprobes. The experimental results demonstrated that the constructed SERS immunosensor exhibited satisfactory selectivity and reproducibility while possessing detection limits as low as 0.908 pg/mL and 0.813 pg/mL for survivin and OPN in human serum. Finally, its usefulness in real serum samples (from healthy subjects, cervical intraepithelial neoplasia 1 (CIN 1), CIN 2, CIN 3 and cervical cancer patients) was verified, and the detection data were in good agreement with the enzyme-linked immunosorbent assay results. This immunosensor has excellent performance, which is promising for the early screening of cancer. The ordered single-layer gold film and monolayer SiO2 array were obtained by the oil–water interface self-assembly method and Langmuir-Blodgett (LB) gas–liquid interface assembly method, respectively. Then, these two ordered structures are combined to prepare Au@SiO2 array substrates. This ordered array substrate not only ensures good uniformity, but also improves SERS performance. [ABSTRACT FROM AUTHOR]

Ultrasensitive detection of specific biomarkers in clinical serum is helpful for early diagnosis of cervical cancer. In this paper, a surface-enhanced Raman scattering (SERS)-based immunoassay was developed for the simultaneous determination of squamous cell carcinoma antigen (SCCA) and osteopontin (OPN) in cervical cancer serum. Au-Ag nanoshuttles (Au-AgNSs) as SERS tags and hydrophobic filter paper-based Au nanoflowers (AuNFs) as capture substrate were constructed into a sandwich structure which served as an ultrasensitive SERS-based immunoassay platform. Finite difference time domain simulation confirmed that the electromagnetic field coupled between the AuNFs had a prominent SERS signal enhancement effect, which improved the detection sensitivity. SERS mapping showed that hexadecenyl succinic anhydride hydrophobic treatment could prevent the analyte from being quickly absorbed by the filter paper and increase the retention time to be more evenly distributed on the filter paper substrate. The immunoassay platform was verified to have good selectivity and reproducibility. With this method, the detection limits of SCCA and OPN in human serum were as low as 8.628 pg/mL and 4.388 pg/mL, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects; cervical intraepithelial neoplasia I (CINI), CINII, and CINIII; and cervical cancer patients were analyzed, and the reliability of the results was confirmed by enzyme-linked immunosorbent assay experiments. The constructed SERS-based immunoassay platform could be used as a clinical tool for early screening of cancers in the future. [ABSTRACT FROM AUTHOR]

Detecting microRNA (miRNA) biomarkers expression is of great significance for the diagnosis and treatment of lung cancer. Surface-enhanced Raman scattering (SERS) has achieved microRNA sensing for the diagnosis of primary liver cancers. In this work, we developed a SERS technology for the rapid detection of lung cancers-related miRNA (miR-196a) using bimetallic Au-Ag nanowire (AgNW@AuNPs) substrates coupled with the target hairpin DNA. The finite-difference time-domain simulation proved that a large number of "hot spots" were generated between the AgNW and AuNPs, which resulted in a huge enhancement of the signal of Raman reporters. Filter paper treated by hexadecenyl succinic anhydride hydrophobic and modified with AgNWs@AuNPs was used as capturing substrate. The detection limits of miR-196a in PBS and serum were as low as 96.58 aM and 130 aM, respectively. Studies on nonspecific sequence and single-base mismatch of miRNA demonstrated that SERS-based platform was highly selective, excellent uniform, and reproducible. Finally, the platform was used to show that the miR-196a expression in the serum of lung cancer patients was much higher than that in healthy people. The detection results indicated that the SERS platform had potential applications in cancer diagnosis and might be a viable alternative to the conventional miRNA detection method, the real-time polymerase chain reaction (RT-PCR) technology. [ABSTRACT FROM AUTHOR]

Research methods for DNA detection have been widely extended since the application of nanotechnology, but it remains a challenge to detect specific DNA sequences or low abundance genes in biological samples with accuracy and sensitivity. Herein, a novel biosensor is proposed for the analysis of target DNA in maize based on a high-density "hot spot" surface-enhanced Raman scattering (SERS) substrate and hybridization chain reaction (HCR) amplification strategy. Finite-difference time-domain (FDTD) simulation confirmed that the electromagnetic field enhancement at the gaps between the adjacent Au nanoflowers (AuNFs) was much richer than that around a single AuNF, indicating that the aggregated AuNFs had a good SERS signal amplification effect. Based on the high-density "hot spots" AuNF substrate, the HCR of biotin-hairpin DNA (bio-H1 and bio-H2) could be triggered by the existence of target DNA and a long double-stranded DNA (dsDNA) could be formed rapidly. Due to the biotin and streptavidin (SA) interaction, SERS probes prepared by modifying biotin-DNA-cyanine 5 (bio-DNA-Cy5) on the surface of Ag–Au core–shell nanorods (Ag–AuNRs) could be assembled along the dsDNA, causing significant signal enhancement. The developed biosensor displayed a significant sensitivity with a broad detection range covering from 0.01 to 1 × 104 fM, and the limit of detection (LOD) was as low as 6.31 aM. Moreover, SERS was applied to detect target DNA in maize extract to verify the feasibility of the detection strategy. This strategy could not only carry out the ultrasensitive detection of target DNA but also provide an informative supplement to the SERS biosensing platform. [ABSTRACT FROM AUTHOR]

The high incidence of premature rupture of membranes (PROM) is closely related to the lack of screening methods. Herein, a rapid and sensitive detection model for procalcitonin (PCT) and interleukin-6 (IL-6) was established utilizing the principle of antigen antibody binding and combined with surface enhanced Raman spectroscopy (SERS) and immunochromatographic assay (ICA), which could be used for the detection of specific biomarkers at a low concentration of peripheral blood and early detection of PROM patients. 5,5′-Dithiobis-2-nitrobenzoic acid labeled monoclonal anti-IL-6 on gold nanocages (GNCs) and 4-methylthiobenzoic acid labeled monoclonal anti-PCT on GNCs were employed as SERS tags. In the presence of IL-6 and PCT, the antigen-SERS tag complexes were trapped and concentrated on the two test lines. The unique characteristics of GNCs with hollow and multi-branch angle allowed high SERS performance in the system by increasing the biological binding sites and hot spots. Through finite difference time domain simulation, it could be concluded that the electromagnetic field between the gaps of GNC dimers was stronger than that of the single GNC, which proved the feasibility of ICA based on surface enhanced Raman scattering (SERS-ICA) in theory. The detection limits of IL-6 and PCT in phosphate buffer were 7.897 pg mL−1 and 7.725 pg mL−1, meanwhile the detection limits of peripheral blood were 8.414 pg mL−1 and 8.017 pg mL−1, respectively. In addition, the detection of real-world samples showed that SERS-ICA was available to evaluate the concentrations of IL-6 and PCT. The experimental data of SERS-ICA were in accordance with that of enzyme-linked immunosorbent assay. These results indicated that SERS-ICA had great potential in the early screening of PROM. [ABSTRACT FROM AUTHOR]

Circulating tumour DNAs (ctDNAs) have been reported to be associated with real-time information of progression; however, an accurate and sensitive method has not been established. Herein, a novel dual-signal amplification strategy based on a pump-free surface-enhanced Raman scattering (SERS) microfluidic chip and a catalytic hairpin assembly (CHA) technique was developed for the dynamic monitoring of BRAF V600E and KRAS G12V, which are two non-small cell lung cancer (NSCLC)-related ctDNAs. In the presence of targets, CHA reactions can be triggered between two hairpin DNAs, fixing Pd-Au core-shell nanorods (Pd-AuNRs) onto the magnetic beads (MBs) surface. Thereafter, the composite structures can assemble under the action of magnet, enabling dual-amplification of SERS signal. Using this strategy, the limit of detection (LOD) was low (i.e. at the aM level) in serum. Furthermore, the entire chip-based analysis process could be completed within 5 min, eliminating manual incubation and heavy-duty injection pumps. The selectivity, reproducibility and uniformity of the proposed pump-free SERS microfluidic chip were satisfactory. This superior analysis strategy was finally applied to quantify BRAF V600E and KRAS G12V in tumour-bearing nude mice serum, the results of which corresponded with those of real-time polymerase chain reaction. Overall, this study provides a promising alternative tool for the dynamic monitoring of ctDNA expression level which can benefit the clinical diagnosis of NSCLC. • CHA-induced powerful cycle amplification and the aggregation effect caused by MBs significantly enhanced the sensitivity of proposed pump-free SERS microfluidic chip, with the LODs low to aM level. • The pump-free SERS microfluidic chip presented satisfactory uniformity, stability, specificity and reproducibility. • This dual-signal amplification strategy could be applied for the dynamic monitoring expression of ctDNA in mice serum at different stages. [ABSTRACT FROM AUTHOR]