Ultrasensitive SERS Sensors For Simultaneous Detection Of Multiple Cancer-related Nucleic Acids

Cancer-related nucleic acids in serum have been identified as useful biomarkers to reveal hidden or potential cancers or other diseases.The development of ultrasensitive analysis technique for combination assay of cancer associated serum biomarkers is an effective method for early cancer screening and diagnosis.Surface-enhanced Raman spectroscopy(SERS),known as an ultrasensitive method has been recognized as a powerful tool for trace and multicomponent analysis.In this thesis highly sensitive and specific SERS sensors for simultaneous detection of cancer-associated nucleic acids were proposed.The main works are as follows:(1)An ultrasensitive SERS sensor chip was prepared based on an Ag nanorod array SERS substrate by assembling special hairpin-shaped molecular beacons(MBs)for the detection of multiple lung cancer-related mi RNA biomarkers.The portable SERS sensor exhibits excellent performance for qualitative and quantitative detection of mi RNAs,with advantages of ultra-sensitivity,good specificity,uniformity,reproducibility and stability,as well as remarkable reusability.The limit of detections of the three mi RNAs in human serum are 393 a M,176 a M,and 144 a M,respectively.(2)A liqid SERS sensor for mi RNA was prepared by assembling tetrahedral DNA onto branched gold coated magnetic nanoparticles(B-GMNPs).The Fe3O4-Au core-branched gold shell nanoparticles with improved SERS performance were prepared by the seed-mediated method together with the shape induction agent Ag NO3.The SERS sensor can capture target mi RNA and then recognized comlementary SERS tags to form sandwich-structured compounds which can be seperated and concentrated by external magnetic field for SERS meaurements.The experiment results indicate that highly sensitive and specific detections can be obtained by the proposed SERS sensor and the LOD of mi RNA-21 in serum is 623 a M.(3)An ultrasensitive SERS sensor for detecting multiple nucleic acids was prepared by assembling tetrahedral DNA onto Ag nanorod array SERS substrate.The portable SERS sensor exhibits excellent performance for qualitative and quantitative detection of nucleic acids in virtue of increasing SERS “hot spots”,with advantages of ultra-sensitivity,good specificity,uniformity,reproducibility.The wide linear detection ranges are from 100 a M to 1 n M,and the LODs are estimated to be 50 a M for Target 1 and 66 a M for Target 2,respectively.The results also indicate that the SERS sensor can simultaneously and specifically distinguish between the corresponding target DNAs and random DNAs or proteins accurately,which is expected to be a feasible method for early cancer screening and diagnosis.