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Detection of tumor biomarkers is of great significance for early diagnosis of cancer. Herein, we fabricated a novel lab-on-a chip surface-enhanced Raman scattering (SERS) (LoC-SERS) biosensing platform for highly sensitive and specific detection of thrombin and platelet-derived growth factor-B (PDGF-B) using aptamer recognition technology. This strategy relies on the specific aptamer recognition between SERS probes (Ag–Au core–shell nanorods (Ag–AuNRs) modified with Raman reporter molecules and detection aptamer) and SERS capture substrate (Au nanoflower (AuNF) substrates modified with capture aptamer), which significantly amplify the plasmonic coupling effect that allows the ultrasensitive and high specificity SERS detection. The limits of detection (LODs) are as low as 3.62 fM for thrombin and 2.86 fM for PDGF-B. Such LoC-SERS platform is further employed to simultaneously detect two types of gastric carcinoma-related with high sensitivity and specificity, which meanwhile exhibit robust capacity of resisting disturbance in practical samples. The results revealed that the present LoC-SERS platform displayed excellent analytical performance, including superior reproducibility, specificity, and sensitivity. Satisfactory results were obtained in real sample analysis with the LoC-SERS platform. [ABSTRACT FROM AUTHOR]

A novel surface-enhanced Raman scattering and lateral flow assay (SERS–LFA) biosensor with multiple channels based on an aptamer has been proposed in this work. The developed biosensor was designed for the rapid, convenient, sensitive and specific detection of vascular endothelial growth factor (VEGF) and osteopontin (OPN) in several samples simultaneously. During the assay, VEGF and OPN were recognized by detection aptamers immobilized on cuprous oxide nanocubes (Cu2O NCs) and captured by capture aptamers to form a sandwich structure on the test lines. In this way, generous numbers of "hot spots" formed by the aggregation of Cu2O NCs remarkably enhanced the SERS signals of Raman reporters (NBA and 4-ATP). The detection limits were as low as 0.78 pg mL−1 for the VEGF and 0.86 pg mL−1 for OPN in the human serum within 15 min, respectively. Additionally, the biosensor possesses favorable specificity, reproducibility, uniformity and stability. In the clinical analysis of serum specimens, patients with cervical cancer can be differentiated from healthy volunteers. Consequently, the presented aptamer-based SERS–LFA biosensor with multiple channels provides a powerful tool for the early diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Circulating tumour DNA (ctDNA) has emerged as an ideal biomarker for the early diagnosis and prognosis of gastric cancer (GC). In this work, a pump-free, high-throughput microfluidic chip coupled with catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) as the signal cascade amplification strategy (CHA–HCR) was developed for surface-enhanced Raman scattering (SERS) assays of PIK3CA E542K and TP53 (two GC-related ctDNAs). The chip consisted of six parallel functional units, enabling the simultaneous analysis of multiple samples. The pump-free design and hydrophilic treatment with polyethylene glycol (PEG) realized the automatic flow of reaction solutions in microchannels, eliminating the dependence on external heavy-duty pumps and significantly improving portability. In the reaction region of the chip, products generated by target-triggered CHA initiated the HCR, forming long nicked double-stranded DNA (dsDNA) on the Au nanobowl (AuNB) array surface, to which numerous SERS probes (Raman reporters and hairpin DNA-modified Cu2O octahedra) were attached. This CHA–HCR strategy generated numerous active "hot spots" around the Cu2O octahedra and AuNB surface, significantly enhancing the SERS signal intensity. Using this chip, an ultralow limit of detection (LOD) for PIK3CA E542K (1.26 aM) and TP53 (2.04 aM) was achieved, and the whole process was completed within 13 min. Finally, a tumour-bearing mouse model was established, and ctDNA levels in mouse serum at different stages were determined. To verify the experimental accuracy, the gold-standard qRT–PCR assay was utilized, and the results showed a high degree of consistency. Thus, this rapid, sensitive and cost-effective SERS microfluidic chip has potential as an ideal detection platform for ctDNA monitoring. [ABSTRACT FROM AUTHOR]

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]

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]

An innovative surface-enhanced Raman spectroscopy and lateral flow assay (SERS-LFA) biosensor combined with aptamer recognition had been developed for the convenient, rapid, sensitive and accurate detection of thrombin and platelet-derived growth factor-BB (PDGF-BB) associated with prostate cancer simultaneously. During the biosensor operation, thrombin and PDGF-BB in the sample were recognized and combined by thiol-modified aptamers immobilized on Au–Ag hollow nanoparticles (Au–Ag HNPs) surface and biotinylated aptamers immobilized on the test lines of the biosensor. Thus, thrombin and PDGF-BB were simultaneously captured between detection aptamers and capture aptamers in a sandwich structure. Finite difference time domain simulation confirmed that 'hot spots' appeared at the gaps of Au–Ag HNPs dimer in the enhanced electromagnetic field compared to that of a single Au–Ag HNP, indicating that the aggregated Au–Ag HNPs owned a good SERS signal amplification effect. The detection limits of thrombin and PDGF-BB in human plasma were as low as 4.837 pg ml−1 and 3.802 pg ml−1, respectively. Moreover, the accuracy of the biosensor which was applied to detect thrombin and PDGF-BB in prostate cancer plasma had been verified. This designed biosensor had broad application prospects in the clinical diagnosis of prostate cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection. [Display omitted] • A POCT platform was developed for rapid and sensitive detection of protein markers. • The prepared AuNCA has good SERS signal amplification effect. • The platform can complete the detection of a target in less than 15 min. • The platform has a promising application in clinical testing. [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]

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]

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]

Surface-enhanced Raman spectroscopy (SERS) is a good candidate for the development of fast and easy-to-use diagnostic tools, possibly used on serum in screening tests. In this study, a potential label-free serum test based on SERS spectroscopy was developed to analyze human serum for the diagnosis of the non-small cell lung cancer (NSCLC). We firstly synthesized novel highly branched gold nanoparticles (HGNPs) at high yield through a one-step reduction of HAuCl4 with dopamine hydrochloride at 60°C. Then, HGNP substrates with good reproducibility, uniformity, and high SERS effect were fabricated by the electrostatically assisted (3-aminopropyl) triethoxysilane-(APTES-) functionalized silicon wafer surface-sedimentary self-assembly method. Using as-prepared HGNP substrates as a high-performance sensing platform, SERS spectral data of serum obtained from healthy subjects, lung adenocarcinoma patients, lung squamous carcinoma patients, and large cell lung cancer patients were collected. The difference spectra among different types of NSCLC were compared, and analysis result revealed their intrinsic difference in types and contents of nucleic acids, proteins, carbohydrates, amino acids, and lipids. SERS spectra were analyzed by principal component analysis (PCA), which was able to distinguish different types of NSCLC. Considering its time efficiency, being label-free, and sensitivity, SERS based on HGNP substrates is very promising for mass screening NSCLC and plays an important role in the detection and prevention of other diseases. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are recognized as regulators of gene expression during the biological processes of cells as well as biomarkers of many diseases. Development of rapid and sensitive miRNA profiling methods is crucial for evaluating the pattern of miRNA expression related to normal and diseased states. This work presents a novel hollow Au nanoflowers (HAuNFs) substrate for rapid detection and identification of miRNAs by surface-enhanced Raman scattering (SERS) spectroscopy. We synthesized the HAuNFs by a seed-mediated growth approach. Then, HAuNFs substrates were fabricated by depositing HAuNFs onto the surfaces of (3-aminopropyl)triethoxysilane- (APTES-) functionalized ITO glass. The result demonstrated that HAuNFs substrates had very good reproducibility, homogeneous SERS activity, and high SERS effect. The substrates enabled us to successfully obtain the SERS spectra of miR-10a-5p, miR-125a-5p, and miR-196a-5p. The difference spectra among the three kinds of miRNAs were studied to better interpret the spectral differences and identify miRNA expression patterns with high accuracy. The principal component analysis (PCA) of the SERS spectra was used to distinguish among the three kinds of miRNAs. Considering its time efficiency, being label-free, and its sensitivity, the SERS based on HAuNFs substrates is very promising for miRNA research and plays an important role in early disease detection and prevention. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering (SERS) based on the double-antibody sandwich format is reported for the determination of carcinoembryonic antigen. Ordered gold nanobowl arrays were fabricated and conjugated with anticarcinoembryonic as capturing substrates, and gold nanoshells, adsorbed with 4-mercaptobenzonic acid, were modified with anticarcinoembryonic antigen as labeling tags. After the carcinoembryonic antigen was captured on ordered gold nanobowl arrays, the labeling tags were bonded to the captured carcinoembryonic antigen. The interaction of SERS substrates (ordered gold nanobowl arrays) and SERS labels (gold nanoshells) showed high sensitivity and a low detection limit for carcinoembryonic antigen. The linear dynamic range of SERS for carcinoembryonic antigen was from 5 pg/mL to 100 ng/mL with a linear relationship between carcinoembryonic antigen concentration and SERS intensity. The detection limit was 1.73 pg/mL. SERS detection may be used for other cancer biomarkers and provides potential for the clinical diagnosis of cancer biomarkers. [ABSTRACT FROM PUBLISHER]

In this work, Au nanobowl (AuNB) arrays and the hybridization chain reaction (HCR) were utilized to develop a surface-enhanced Raman scattering (SERS) microfluidic chip for the ultrasensitive and simultaneous detection of squamous cell carcinoma antigen (SCCA) and cytokeratin 19 fragment antigen 21–1 (CYFRA21–1) in the serum of cervical cancer patients. Antibody-oligonucleotide conjugates were adopted as triggers, which initiated HCR by the hybridization between hairpin DNAs that were modified on Raman reporters-labeled Ag nanocubes, forming nicked double-stranded DNAs on AuNB arrays and leading to SERS signal amplification. Good linear response in the range of 10-12 – 10-6 g/mL, with an ultralow limit of detection for SCCA (0.08 pg/mL) and CYFRA21–1 (0.13 pg/mL), was achieved. Furthermore, the experiments demonstrated that the chip was feasible, time-efficient, and selective. The proposed chip was successfully applied to detect SCCA and CYFRA21–1 in clinical samples, and the results were consistent with those of enzyme-linked immunosorbent assay. Since most protein biomarkers in serum lack the corresponding aptamers, this method, which establishes antibody-oligonucleotide conjugates to trigger HCR, provides a general signal amplification technology for detecting protein biomarkers and exhibits good potential in clinical applications. • A SERS microfluidic chip based on AuNBs array and HCR was developed and employed for clinical detection. • Antibody-oligonucleotide conjugates were established to connect with targets and initiate HCR for signal amplification. • The assay possessed high sensitivity, with LODs as low as 0.08 pg/mL for SCCA and 0.13 pg/mL for CYFRA21-1. • The SERS microfluidic chip realized automatic flow by hydrophilic treatment and comb-like structure channels. [ABSTRACT FROM AUTHOR]

Lung resident mesenchymal stem cells (LR-MSCs) are important regulators of pathophysiological processes including tissue repair and fibrosis, inflammation, angiogenesis and tumor formation. Therefore, increasing attention has focused on the functional differentiation of LR-MSCs. However, the distinction between the undifferentiated and differentiated LR-MSCs, which are closely related and morphologically similar, is difficult to achieve by conventional methods. In this study, by employing the TAT Peptide-conjugated Au nanostars (AuNSs) as an intracellular probe, we developed a method for the identification of LR-MSC differentiation by surface-enhanced Raman scattering (SERS) spectroscopy. SERS spectra were analyzed using principal component analysis (PCA) that allowed unambiguous distinction of subtypes and monitoring of component changes during cellular differentiation. Furthermore, to ascertain whether co-culture with alveolar epithelial type II (ATII) cells and incubation with transform growth factor (TGF)-β were involved in regulating the differentiation of LR-MSCs, we investigated the protein expression levels of epithelial markers and fibroblastic markers on LR-MSCs. Our results demonstrated that co-culture with ATII cells or incubation with TGF-β could induce the differentiation of LR-MSCs as confirmed by SERS analysis, a method that is capable of noninvasive characterization of and distinction between subtypes of LR-MSCs during differentiation. We have provided a new tool that may facilitate stem cell research. [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]

There is a challenge to obtain an ultrasensitive and rapid approach to detect bacteria and identify resistance. As a powerful bioanalytical tool, surface-enhanced Raman scattering (SERS) in bacterial detection have attracted increasing attentions. Herein, we developed a SERS-active Au@Ag core-shell nanorod (Au@AgNR) tag platform for ultrasensitive bacteria detection and antibiotic-susceptibility testing (AST). The platform established that surface enhanced Raman scattered Rhodamine 6G (R6G) absorption at 1517 cm−1 had a good linearity (RI = 3865 + 193logC; R2 = 0.97) with logarithm of E. coli concentration over a range of 107–102 CFU (colony forming unit)/mL with limit of detection as low 102 CFU/mL. When E. coli was exposed to ampicillin at minimum inhibitory concentration (MIC, 4 μg/mL), Raman spectroscopy showed the obvious variation between ampicillin-susceptible E. coli (Amp−- E. coli) and the ampicillin-resistant E. coli (Amp+- E. coli). Combined with principal component analysis (PCA) statistical analysis, the Raman intensity variation mentioned above allows to obtain rapid antibiotic resistance testing (<3.5 h). In addition, E.coli spiked into blood from C57BL/6 mice can be identified clearly, indicating the potential for point-of-care diagnostics. Image 1 • Ultrasensitive and rapid approach to detect bacteria and identify resistance. • SERS nanotags can specifically anchor onto E.coli. • Raman intensity collected from the SERS nanotags bound E. coli is proportional to logarithm of E. coli concentration. • Combined with PCA, the Raman intensity statistical analysis allows to obtain rapid antibiotic resistance testing. [ABSTRACT FROM AUTHOR]

[Display omitted] • A competitive recognition binding strategy regarding the aptamer was designed. • An integrated SERS-enabled LoC system was fabricated for gastric cancer detection. • VEGF and PDGF-B in human serum was directedly quantified with an ultralow LOD. Multiplex detection of biomarkers is nontrivial for gastric cancer diagnosis. Herein, we presented a lab-on-a-chip surface-enhanced Raman scattering (LoC-SERS) sensing system for the detection of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-B (PDGF-B). The sensing system includes three parallel channels, each channel consists of two detection chambers, enabling the simultaneous analysis of multiple samples. The capillary structure provides self-driving power without the need of external pumps. The ordered gold nano-bipyramids (GNBPs) array in the detection chamber can form uniform and dense "hot spots", due to the homogeneous double-tip structure and narrow gaps, resulting in better SERS performance. During the analysis process, VEGF and PDGF-B in the serum can lead to the change of aptamer conformation. Raman reporter-labeled complementary DNA is shed from the aptamer due to competition of the target. The entire process only requires 20 min, which is rapid. By monitoring the changes in Raman intensity and fitting it with the logarithm of concentration, the correlation between the intensity and concentration can be clearly reflected as a mathematical relationship. The LoC-SERS sensing system has been verified to have excellent selectivity and reproducibility. Via the sensing system, the limits of detection (LOD) of VEGF and PDGF-B are as low as 0.342 pg/mL and 0.265 pg/mL in serum, respectively. In addition, the accuracy was verified through enzyme-linked immunosorbent assay (ELISA). Therefore, the proposed LoC-SERS sensing system has great potential for clinical detection of gastric cancer. [ABSTRACT FROM AUTHOR]

Serum analysis is crucial for favourable prognosis of gastric cancer (GC) and for improving patient survival rates. However, it remains a challenge to develop an effective strategy to accurately identify differences in gastric cancer before and after treatment to guide efficacy evaluation. In this study, we combined surface-enhanced Raman scattering (SERS) with principal component analysis (PCA)-two-layer nearest neighbour (TLNN) to propose a promising serum analytical platform for label-free detection of cisplatin-treated GC mice. A microarray chip fabricated from Au nano-hexagon (AuNH) substrates was employed to measure the SERS spectra of the serum of GC mice at different treatment stages, and then a model for recognition of SERS spectra was constructed using a PCA-TLNN algorithm. The results revealed that the microarray chip exhibited superior portability, SERS activity, stability, and uniformity. Through PCA-TLNN, the GC mice at different treatment stages were successfully segregated, and several key spectral features for distinguishing different treatment stages were captured. The established PCA-TLNN model achieved satisfactory results, with an accuracy of over 97.5%, a sensitivity of over 90%, and a specificity of over 96.7%. Label-free serum SERS in combination with multivariate analysis could serve as a potential technique for the clinical diagnosis and staging of treatments. [Display omitted] • The novel microarray chip can realize rapid, sensitive, label-free and high-throughput detection of SERS spectra of serum. • PCA-TLNN successfully differentiated the SERS spectra of serum from cisplatin-treated GC mice at different stages. • The most prominent spectral features for distinguishing different treatment stages. • were captured in PCs loading plots. • PCA-TLNN was superior to traditional multivariate algorithm in accuracy, sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Early and precise diagnosis of lung cancer is critical for a better prognosis. However, it is still a challenge to develop an effective strategy for early precisely diagnose and effective treatments. Here, we designed a label-free and highly accurate classification serum analytical platform for identifying mice with lung cancer. Specifically, the microarray chip integrated with Au nanostars (AuNSs) array was employed to measure the surface-enhanced Raman scattering (SERS) spectra of serum of tumor-bearing mice at different stages, and then a recognition model of SERS spectra was constructed using the principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) algorithm. The microarray chip can realize rapid, sensitive, and high-throughput detection of SERS spectra of serum. RCKNCN based on the PCA-generated features successfully differentiated the SERS spectra of serum of tumor-bearing mice at different stages with a classification accuracy of 100%. The most prominent spectral features for distinguishing different stages were captured in PCs loading plots. This work not only provides a practical SERS chip for the application of SERS technology in cancer screening, but also provides a new idea for analyzing the feature of serum at the spectral level. [Display omitted] • A rapid, sensitive, label-free, high-throughput SERS microarray chip was developed. • Combining SERS with PCA-RCKNCN successfully differentiated the SERS spectra. • The most prominent spectral features of SERS spectra in PCs loading were captured. • PCA-RCKNCN was superior to traditional multivariate algorithm in accuracy. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a major histologic category of lung cancer. In this paper, a new type of surface-enhanced Raman scattering (SERS) microfluidic chip proposed for the simultaneous and efficient detection of miR-92a and miR-339-3p, two microRNAs (miRNAs) related to NSCLC. In addition, the method was used to detect miR-92a and miR-339-3p in the serum of NSCLC clinical samples, and the results were consistent with the quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, this new SERS microfluidic chip is a very promising tool for detecting miRNA expression levels, which can help in the early diagnosis and prognosis of NSCLC. [Display omitted] • SERS effect of the Au-AgNBs array is excellent, which improves the sensitivity of SERS analysis. • The hydrophilic-treated SERS microfluidic chip combined with the hpDNA- functioned Au-AgNBs array eliminates the need for an external driver while improving detection efficiency. • The LOD of the SERS microfluidic chip reaches aM level, and the detection and analysis time is as low as 8 min. • The device can be used for the early diagnosis of non-small cell lung cancer to improve cancer survival rates. In this paper, a novel surface-enhanced Raman scattering (SERS) microfluidic chip is proposed for the simultaneous and efficient detection of miR-92a and miR-339-3p, two microRNAs (miRNAs) related to non-small cell lung cancer (NSCLC). The sample solution can flow along the microchannel into the reaction zone during the assay, driven by the capillary force generated by the comb-like structured channel. A one-step paired hybridization reaction with the corresponding hairpin DNA (hpDNA) on the hpDNA-functioned Au-Ag nanobowl (Au-AgNBs) array takes place when the target strand is present in the sample solution, amplifying the SERS signal. The detection limits of miR-92a and miR-339-3p in serum were 44.36 aM and 63.58 aM, respectively, using this method, with a detection and analysis time of only 8 min. The microfluidic chip showed good specificity, reproducibility, and stability. Finally, the method was used to detect miR-92a and miR-339-3p in the serum of NSCLC clinical samples, and the results were consistent with the quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, this new SERS microfluidic chip is a very promising tool for detecting miRNA expression levels, which can help in the early diagnosis and prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA), as one of the ideal target biomarker analytes, plays an essential role in biological processes; thus, the development of rapidly sensitive detection methods is imperative. Herein, we proposed a pump-free surface-enhanced Raman scatting (SERS) microfluidic chip for the rapid and ultrasensitive detection of miR-106b and miR-196b, laryngeal squamous cell carcinoma (LSCC)-related miRNAs. Ag–Au core-shell nanorods (Ag-AuNRs) were applied to prepare SERS tags by modifying Raman reporters and hairpin DNAs. The capture probes were synthesized by labeling hairpin DNAs onto the magnetic beads (MBs) surface. In the presence of targets, the catalytic hairpin assembly (CHA) reactions between SERS tags and capture probes could be triggered, causing the aggregation of Ag-AuNRs. The tiny magnets installed under the rectangular chamber could magnetically gather the CHA products, leading to the further aggregation of Ag-AuNRs. Thus, this strategy could achieve the double aggregation of Ag-AuNRs, resulting in the significant amplification of the SERS signal. The proposed strategy achieved simultaneous and sensitive detection of miR-106b and miR-196b, with limits of detection low to aM level. The whole detection process could be completed within 5 min. Moreover, this microfluidic chip exhibited excellent reproducibility, stability, and specificity. The high accuracy of this SERS microfluidic chip was proved by practical analysis in LSCC patients' serum. The results demonstrated that SERS could be a promising alternative clinical diagnosis tool and exhibited potential application for the dynamic monitoring of cancer staging. A pump-free SERS microfluidic chip coupling with CHA amplification is fabricated for the ultrasensitive and simultaneous detection of miR-106b and miR-196b. [Display omitted] • To our knowledge, this is the first report demonstrating pump-free SERS microfluidic chip coupling with catalytic hairpin assembly (CHA) reaction for detection of miR-106b and miR-196b simultaneously. • Dual signal amplification composed of CHA-induced powerful cycle amplification and the aggregation effect caused by MBs enables the ultrasensitive detection of miRNA, with the LODs low to aM level. • The entire detection process could be finished less than 5 min. • Excellent uniformity, stability, specificity and reproducibility of this pump-free SERS microfluidic chip are demonstrated. [ABSTRACT FROM AUTHOR]

Accurate quantification of multiple miRNAs biomarkers in body fluid is still a challenge for early screening of cancer. Herein, by catalytic hairpin assembly as a signal amplification strategy, we designed a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) strip for ultrasensitive detection of miR-21 and miR-196a-5p in non-small cell lung cancer (NSCLC) urine on a single test (T) line. 4-mercaptobenzoic acid or 5,5′-dithiobis-2-nitrobenzoic acid as Raman molecules was labeled and two hairpin DNA sequence was modified gold nanocages (GNCs) were designed as two SERS tags. Through target miRNA-triggered catalytic hairpin assembly (CHA), the double-stranded DNAs (H1–H2 complex) formed by SERS tags and the related hairpin-structured DNA sequence 2 (H2) were immobilized on a single T line of SERS-LFA strip. This generated abundant "hot spots" because of the formation of numerous H1–H2 complex thus facilitated the SERS measurement. Through this method, two kinds of miRNAs were analyzed, resulting in limits of detection of 2.08 pM and 3.31 pM for miR-21 in PBS buffer and human urine, 1.77 pM and 2.18 pM for miR-196a-5p in PBS buffer and human urine. Significantly, the SERS-LFA strip exhibited high specificity and good repeatability toward miRNAs. The whole detection time was only 30 min, which means that the high detection efficiency of the strip. The clinical feasibility of the proposed method was also evaluated by detecting the levels of miR-21 and miR-196a-5p in urine samples from NSCLC patients and healthy subjects. The developed SERS-LFA strip has wide application prospect in biomedical research, drug development and early clinical diagnosis. A novel surface-enhanced Raman scattering-lateral flow assay strip in combination with catalytic hairpin assembly was developed for rapid, sensitive, and simultaneous detection of multiple non-small cell lung cancer-related miRNAs on a single test line. [Display omitted] • A simultaneous detection of multiple cancer biomarkers by catalytic hairpin assembly-based SERS-LFA strip on a single test line with high sensitivity and accuracy is proposed. • GNCs, as a kind of novel nanomaterial, can be prepared on a large scale and has good SERS reinforcement effect. • Catalytic hairpin assembly-based SERS-LFA strip shows favorable performance in clinical test, which can achieve the LODs as low as 3.31 pM (miR-21) and 2.18 pM (miR-196a-5p) in human urine. [ABSTRACT FROM AUTHOR]