title: Asymmetric signal amplification for simultaneous SERS detection of multiple cancer markers with significantly different levels.
abstract: Simultaneous detection of cancer biomarkers holds great promise for the early diagnosis of different cancers. However, in the presence of high-concentration biomarkers, the signals of lower-expression biomarkers are overlapped. Existing techniques are not suitable for simultaneously detecting multiple biomarkers at concentrations with significantly different orders of magnitude. Here, we propose an asymmetric signal amplification method for simultaneously detecting multiple biomarkers with significantly different levels. Using the bifunctional probe, a linear amplification mode responds to high-concentration markers, and quadratic amplification mode responds to low-concentration markers. With the combined biobarcode probe and hybridization chain reaction (HCR) amplification method, the detection limits of microRNA (miRNA) and ATP via surface-enhanced Raman scattering (SERS) detection are 0.15 fM and 20 nM, respectively, with a breakthrough of detection concentration difference over 11 orders of magnitude. Furthermore, successful determination of miRNA and ATP in cancer cells supports the practicability of the assay. This methodology promises to open an exciting new avenue for the detection of various types of biomolecules.
authors.affiliation: †College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P.R. China.|‡Key Laboratory of Sensor Analysis of Tumor Marker Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P.R. China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Ye
authors.affiliation: ‡Key Laboratory of Sensor Analysis of Tumor Marker Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P.R. China.
authors.forename: Yanying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: ‡Key Laboratory of Sensor Analysis of Tumor Marker Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, P.R. China.
authors.forename: Xiaomo
authors.initials: X
authors.lastname: Zhai
authors.affiliation: †College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D001681:Biological Assay / Q000379:methods*; D014408:Biomarkers, Tumor / Q000097:blood*; D015374:Biosensing Techniques / Q000379:methods*; D006046:Gold / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D053768:Metal Nanoparticles / Q000737:chemistry; D059629:Signal-To-Noise Ratio
chemical_list: D014408:Biomarkers, Tumor; D006046:Gold