SERS spectroscopy using Au-Ag nanoshuttles and hydrophobic paper-based Au nanoflower substrate for simultaneous detection of dual cervical cancer–associated serum biomarkers

• Published in: Analytical and bioanalytical chemistry Vol. 412; no. 26; pp. 7099 - 7112
• Main Authors: Lu, Dan, Ran, Menglin, Liu, Yifan, Xia, Ji, Bi, Liyan, Cao, Xiaowei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2020; Springer; Springer Nature B.V
• Subjects: Adult; Analytical Chemistry; anhydrides; Antigens; Biochemistry; Biological markers; Biomarkers; Biomarkers, Tumor - blood; Biomedical materials; blood serum; Cancer; Cervical cancer; Cervix; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; detection limit; Detection limits; Diagnosis; early diagnosis; electromagnetic field; Electromagnetic fields; Electromagnetism; Enzyme-linked immunosorbent assay; Female; Filter paper; Finite difference time domain method; Food Science; Gold; Gold - chemistry; Human papillomavirus; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Immunoassay; Immunoassay - methods; Laboratory Medicine; Limit of Detection; Mapping; Metal Nanoparticles - chemistry; Monitoring/Environmental Analysis; nanoflowers; Osteopontin; Raman spectra; Raman spectroscopy; Reliability analysis; Research Paper; Retention time; Sandwich structures; Selectivity; Silver; Silver - chemistry; Spectroscopy; Spectrum Analysis, Raman - methods; Squamous cell carcinoma; Substrates; uterine cervical neoplasms; Uterine Cervical Neoplasms - blood; Uterine Cervical Neoplasms - diagnosis; Young Adult; China; Osteopontin; Squamous cell carcinoma antigen; Surface-enhanced Raman scattering; Au nanoflowers; Au-Ag nanoshuttles; Cervical cancer
• ISSN: 1618-2642; 1618-2650; 1618-2650
• DOI: 10.1007/s00216-020-02843-x

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.