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In this work, a microfluidic chip using Au@SiO2 array–based highly active SERS substrates was developed for quantitative detection of squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) associated with cervical cancer. The chip consisted of six functional units with pump-free design, enabling parallel detection of multiple samples in an automatic manner without external pumps and improving the portability. Ag nanocubes (AgNCs) were labeled with Raman reporters and coupled with antibodies (labeling) to prepare SERS tags, while the Au nanoparticle–modified SiO2 microsphere (Au@SiO2) array was conjugated with antibodies (coating) to generate the highly SERS-active capturing substrate. In the presence of target biomarkers, they were captured by SERS tags and capturing substrate, resulting in the formation of "sandwich" structures which were trapped in the detection chamber. As the immune reaction proceeded, a large number of "hot spots" were generated by the proximity of the Au@SiO2 array substrate and AgNCs, greatly amplifying SERS signals. With this chip, the limits of detection of the SCCA and CEA levels in human serum were estimated to be as low as 0.45 pg mL−1 and 0.36 pg mL−1, respectively. Furthermore, the good selectivity and reproducibility of this chip were confirmed. Finally, clinical serum samples were analyzed by this chip, and the outcomes were consistent with those of enzyme-linked immunosorbent assay (ELISA). Thus, the proposed microfluidic chip can be potentially applied for the clinical diagnosis of cervical cancer. [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]

A CoNi-based metal–organic framework (CoNi-MOF) nanosheet array is synthesized by the treatment of a CoNi layered double hydroxide nanosheet array on Ni foam with 3,5-diaminobenzoic acid. The CoNi-MOF nanosheet array with amino and carboxyl groups can be used to capture the human chorionic gonadotropin (HCG) primary antibody (HCG Ab1). Nile Blue decorated ZnNi-MOF (NB@ZnNi-MOF) spheres immobilized with HCG secondary antibodies (HCG Ab2) are used for signal amplification. When HCG exists in an analytical sample, a sandwich structure is formed and an electrochemical signal is produced. The analytical signal generated during the detection is caused by the conversion of Co(II) and Co(III) in the CoNi-MOF nanosheet array. The Nile Blue of the NB@ZnNi-MOF sphere, as a kind of redox-active species, is responsible for the electrochemical signal amplification in the immunosensor. On the basis of the above advantages, the HCG immunosensor exhibits a lower limit of detection (1.85 × 10−3 mIU mL−1) and a wide linear range from 0.005 mIU mL−1 to 250 mIU mL−1. Additionally, this immunosensor is used to quantitatively detect HCG in human blood serum and shows good correlations with the standard enzyme-linked immunosorbent assay (ELISA), providing a high value on clinical diagnosis. [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]

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]

[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]

Procalcitonion (PCT) have been proved to be disease-related markers of premature rupture of membranes (PROM) in serum of patients. Therefore, the profiling technology of rapid and sensitive is crucial for detecting the level of PCT in human serum, which is of great significance for early diagnosis and treatment of PROM. In this work, the surface-enhanced Raman scattering (SERS) detection platform combined with double antibody sandwich method was used to quantitatively detect PCT in serum of patients with PROM. A highly sensitive, uniform, and reliable SERS substrate was fabricated by assembling Ag nanowires (AgNWs) on the hydrophobic filter paper treated with alkyl ketene dimer (AKD). Then hollow Au nanocages (HAuNCs) with SERS activity were synthesized facilely. The SERS immunoassay system consists of SERS tags and capturing substrate. HAuNCs labled anti-PCT (labeling) were used as SERS tags. Filter paper modified with AgNWs and anti-PCT (coating) was used as capturing substrate. When the SERS immunoassay system were used to directly detect PCT antigen, Raman intensity at different PCT antigen concentrations (1 pg/mL-1 μg/mL) was linearly related to the logarithm of PCT antigen concentration. By establishing a calibration curve within a certain range, it can be concluded that the detection limits of PBS and human serum were as low as 2.86 pg/mL and 3.74 pg/mL respectively. Serum samples from PROM patients were detected by SERS, and the results were consistent with those of the enzyme-linked immunosorbent assay (ELISA). Furthermore, The high reproducibility and homogeneity of SERS immunoassay were confirmed. Above results demonstrated the feasibility and great potential for developing this new SERS immunosensor into a clinical tool for sensitive analysis of biomarkers in human serum. [ABSTRACT FROM AUTHOR]