New Strategies Of Highly Reliable SERS Detection And Their Application In Sensing Analysis Under Complex Conditions

The fast development of Surface-enhanced Raman spectroscopy(SERS),owning many advantages of high sensitivity,high spectral resolution,no influence of water and etc.,can be utilized for not only direct detection,but also indirect detection by means of derivative or sensing strategies.Based on accumulation and development during more than 40 years,especially due to the appearance of noble metal nanoparticles(NPs)-based enhanced substrates,SERS fully embodies its advantages of high sensitivity and selectivity into the fields of label/label-free detection,biosensor,cell imaging and even in vivo analysis.The expansion of SERS-related research has been envolved from synthesis of Au/Ag nanostructures to fabrication of practical SERS-active device;from single component to multiplex detection under complex conditions;from label-free imaging of single organelles to multi-color cellular imaging;from ex vivo cellular imaging to in vivo imaging of animals or plants.All the above-mentioned studies demonstrated that SERS-related applied research have been changed from spectral analysis depending on the whole spectrum to accurate analysis depending on single unique bands,which will attract more attention of researchers in various fields,such as analytical chemistry,biology,pharmacology,environmental and catalytic sciences.However,the application of SERS in various fields is far from perfect.It is necessary to develop highly practical and reliable SERS techniques,focusing on the preparation of reproducible substrates,design and synthesis of high discerned Raman reporter molecules,the construction of highly selective detection strategies.Based on it,this paper proposed several novel strategies on how to improve the reliability of SERS-based sensing techniques under complex conditions,and it has been successfully applied to the real sample.The detailed contents of the research are as follows:1.Field,reliable and ultrasensitive detection of dipicolinic acid(DPA),a general biomarker of bacterial spores,is highly desirable but still challenging in current biometric security emergency response system.Herein we report for the first time an environmentally safe mercury(?)was used as mediatedions,which can efficiently complex with DPA and remove the interferences immediately,such as tyrosine,phenylalanine,cysteine and DNA.By means of the competitiveness between papain capped gold nanoparticles(P-AuNPs),DPA and Hg2+,enabling reliable,rapid,and ultrasensitive detection of DPA without the pretreatment of samples.2.As an important indicator of human health,the reliable and sensitive detection of thiocyanate(SCN-)is still urgently needed.We successfully fabricated a super stable and practical test reagent for detection of SCN-,by the anchor of Raman signal molecules,which was lying at 2208 cm-1 in biological silence region,onto the gold core of the Au@Ag nanoparticles,under the assembly and protection of hexadecyl trimethylammonium bromide(CTAB),the test reagent has no change after placing 3 months.It was also applied to the detection of SCN-in body fluid(saliva,serum and urine)and food(milk power and brassica vegetables),and its sensitivity and linear range were superior to the technology of ion chromatography and UV-vis spectrophotometry.3.The simple,rapid and accurate serodiagnosis of cancer biomarkers is critically important for the clinical diagnosis and prognosis of cancer.SERS owns obvious advantages in simultaneous detection of multiple cancer biomarkers due to its high spectral specificity.On the basis of our previous work,in the aid of three different signal molecules with Raman shift at 2105,2159 and 2227 cm-1 in biological silence region,these three encoded SERS tags were then conjugated with different antibodies.The simultaneous,interference-free detection of AFP,CEA,and FER in 43 clinical serum samples has been realized by our SERS-based immunoassay,through the formation of simple and reliable sandwich structure by antibody(SERS tag)-antigen(biomarkers)-antibody(magnetic beads).According to the diagnosis results,the liver cancer screening accuracy based on detection of single AFP,dual AFP and CEA,and triple AFP,CEA and FER has been demonstrated to increase significantly.Therefore,our SERS-based immunoassay is superior to the existing clinical diagnosis method on simplicity and sensitivity.4.As an important biomarker,the abnormal value of alkaline phosphatase(ALP)can indicate the lesion in bone,kidney and liver,even certain types of cancer,it is significant to detect ALP in clinic.We proposed a method for controllable SERS detecion of ALP.Ag+ was firstly used as mediated ions,which can induce the SERS tag to form the length controllable chain of gold NPs;on the other hand,in the presence of substrate,Ag+ can be reduced into silver cluster by means of enzymatic catalysis of ALP,leading to the reduce of Ag+.Correspondingly the intensity of the SERS tag will be changed in proportion to ALP,it can be used for detection of ALP.In comparison with traditional uncontrollable aggregation,our controllable SERS-based assay owns superior reliability on detection of ALP.