Surface Enhanced Raman Scattering Sensors In Early Screening And Diagnosing Gastric Cancer

Gastric cancer(GC)is a world-wide life-threaten.In China,GC is the second most common cancer,and causes the third cancer-related mortality.Histologically,GC can be divided into early gastric cancer(EGC,defined as that the tumor invasion is confined to the mucosa or submucosa)and advanced gastric cancer(AGC,defined as that the tumor invades into the muscularis propria or deeper gastric wall).Compared to advanced stage(the five-year-survival rate is less than 24%),early diagnosis can dramatically increase cure rate(the five-year-survival rate is more than 90%).However,more than 80% EGC patients do not have clear and characteristic clinical manifestations.Besides early diagnosis,a preoperative precise staging can provide the individualized treatments and reduce the mortality.Due to the lack of defined risk factors,GC is facing great challenges in its staging system,such as time-bulky,problematic diagnosis and inconvenient suffering among patients caused by gastroscopy or biopsy.Therefore,the delayed diagnosis and inadequacies of staging system lead to an increased mortality.Therefore,it is urgent to develop simple and reliable approaches for early screening and diagnosing GC in the large crowds,and we want to improve the GC treatments by both early diagnosis and accurate staging.The approaches should be non-noninvasive and convenient in sample collections,fast and cheap in detection and effective and reliable in distinguishing EGC and AGC.Therefore,the breath analysis based on the volatile organic compounds(VOC)in our breath and salivary diagnostics based on the small metabolites in our saliva are regarded as new windows for the early screening and diagnosing GC as following reasons:(a)breath and saliva samples can be flexibly and accurately collected by non-invasive techniques without any medical consideration;(b)biomarkers in breath and saliva have elucidated pathways with GC and can reflect different pathological states of GC;(c)numerous biomarkers in breath and saliva can eliminate the influence of inter-individual differences.In past,VOCs in breath and small metabolites in saliva as GC biomarkers attract more and more attentions for various cancer diagnosis.In this work,fourteen VOCs biomarkers in breath are identified by using gas chromatography-mass spectrometry(GC-MS)coupled with solid phase microextraction(SPME)to diagnose EGC and AGC.Meanwhile,ten amino acids in saliva are identified as small metabolite biomarkers for AGC and EGC by high performance liquid chromatography-mass spectrometry(HPLC-MS),and their combinations have the potential in diagnosis of EGC and AGC.Furthermore,we facilely develop two different surface enhanced Raman scattering(SERS)sensor based on graphene-materials and Au nanoparticles to detect the biomarker and realize the early screening and diagnosing GC with excellent performance.Therefore,the whole dissertation is composed of four chapters.Chapter 1: we review the situation of GC incidence and mortality,and list the approaches in diagnosis of GC.Then,we introduce the applications and approaches of breath analysis in cancer diagnosis.Furthermore,we also introduce the applications of salivary diagnostics in cancer diagnosis.Meanwhile,we also introduce the SERS and its application in biomedicine area.At last,we outlook the application of the SERS sensor in breath analysis and salivary diagnostics for early screening and diagnosing GC as acceptable ways.Chapter 2: Fourteen VOC biomarkers in breath have been identified to diagnose EGC and AGC by GC-MS coupled with SPME.Then,a breath analysis approach based on clean SERS sensors has been developed to detect those biomarkers.Utilizing hydrazine vapor adsorbed in graphene oxide(GO)film,the clean SERS sensor is facilely prepared by in situ forming AuNPs on reduced graphene oxide(RGO)without any organic stabilizer.In the SERS sensor,RGO can selectively adsorb and enrich the identified biomarkers from breath as SPME fiber,and AuNPs well dispersing on RGO endow the SERS sensor with an effective detection of adsorbed biomarkers.Fourteen Raman bands associated with the biomarkers are selected as the fingerprints of biomarker patterns to distinguish different cancer states.The approach has successfully analyzed and distinguished different simulated breath samples and 200 breath samples.In conclusion,the VOC biomarkers and breath analysis approach in diagnose EGC and AGC in this study.Chapter 3: Ten amino acids in saliva are identified as small metabolite biomarkers for AGC and EGC by HPLC-MS,and their combinations have the potential in diagnosis of EGC and AGC.Then,clean SERS sensors based on graphene oxide wrapped gold nanoparticles nanoscrolls(A/GO NSs)are developed to detect the biomarkers in liquid saliva.The distinctive A/GO NSs are facilely prepared via ultrasonication without any organic stabilizer,and endow the clean SERS sensors with excellent uniformity,stability,selective adsorbability and SERS activity to detect the biomarkers in saliva.In this work,the clean SERS sensors are successfully applied in salivary diagnostics by using 220 saliva samples to build a diagnostics model with excellent blind test result in diagnosing EGC and AGC.Chapter 4: we give a summary of our research work and prospect the development of both breath analysis and salivary diagnostics based on clean SERS sensors.