Novel Raman Optical Labels Fabrication For Biological Detection And Imaging Analysis

Driven by the growing demand for healthcare and real-time detection applications,the current research focus directed towards innovating high-performance optical labels for ultrasensitive biosensing and disease diagnostics in place of conventional optical labels.The water-free interference feature makes Raman optical labels particularly suitable for biomedical applications.Thanks to surface enhancement Raman scattering(SERS),stimulated Raman scattering(SRS)and other signal enhancement methods,Raman optical labels have attracted much attention from scientific and clinical communities and made progress in biomedicine applications.SERS labels represent an intriguing class of optical labels for biosensing and bioimaging applications,mainly attributed to multiple merits from SERS,such as high light stability,easy multiplex encoding,flexibility,less interference from biological matrices,high photostability,etc.However,its practical applications performance in extremely complex biological systems such as body fluids,cells and living tissues needs to be improved.The highly stable and repeatable amplified signals in sensing analysis come from the construction of controllable hotspots,and high-precision imaging analysis requires innovation in signal output modes.Based on the novel Raman label construction and new signal output mode,this paper proposed several novel Raman optical labels on the sensing detection and imaging of pathogenic pollutants and biomarkers in complex biochemical systems.The detailed contents of the research are as follows:1.High sensitive SERS labels fabrication for pathogenic pollutants bisphenol A(BPA)detectionBPA is a kind of pathogenic environmental pollutant that destroys human endocrine system,leading to a reduction in immune function,impaired reproduction.Here we reported chitosan-functionalized Au@Ag nanoparticles as SERS labels,combined with BPA-specific ss DNA aptamers as sensing platforms to allow rapid detection of trace amounts of BPA in tap water.Linear concentration range of this method was 0.01-1 ng/m L,LOD can be as low as 2.8 pg/m L,and the sensitivity was two to three orders of magnitude lower than other reported BPA sensing techniques.2.Novel"click"SERS labels for apoptosis protease caspase-3 detection and cell imagingThe detection and monitoring of apoptosis is of great significance in cell biology and clinical investigations.Here we designed novel"click"SERS labels for detection of caspase-3,the most critical protease in the process of apoptosis,and achieved reliable quantitative analysis and accurate cell imaging result of caspase-3 through new signal output model.The controllable hotspot construction of"click"SERS labels realized by DNA hybridization between poly-A modified Au NPs,which improved the reliability of quantitative analysis.Moreover,Raman silent region signal molecule selected to achieve high-intensity signal background ratio in complex cell systems.The most important part was the combined signal output mode improved accuracy of SERS imaging and reduced false positive signals caused by gravity deposition during the inevitable long-time incubation.3.Novel low-wavenumber region Raman labels for sialic acid(SA)expression imaging on cancer cellsThe specific recognition of cancer cell biomarkers is extremely important for the visualization and treatment of cancer cells.Sialic acid is a monosaccharide that overexpressed at the end of glycoprotein sugar chain on the surface of cancer cells,has emerged as a promising cancer biomarker.We designed novel Raman optical labels that combined Cd Se nanoparticles with aminophenylboronic acid(ABPA)for imaging analysis of sialic acid overexpressed on the surface of cancer cells.Compared with the existing common SERS labels and molecular imprinting fluorescent labels,the novel Raman optical labels were extremely stable during cell activity process,and the small volume with a diameter of only 5 nm reduced false positive signals caused by gravity deposition.The high affinity of APBA for sialic acid improved the specificity of this new Raman labels,and more importantly,the Raman signal output in low-wavenumber region(100-500 cm^-1)reduced the signal interference of many endogenous substances in cancer cells.