Noninvasive In Vivo Microsampling And Direct Mss Spectrometry Analysis Of Environmental Exposures And Disease Metabolites In Human Tears

Human tear fluid is one of complex body fluids secreted by the lacrimal gland.There is an extreme volume of tears in human eyes where scrests about 5-10 μL tears of for a human eye per day.The changes of tears volume and composition are closely related to human pathological conditions and environmental exposure.Therefore,human tear analysis plays a key role in revealing environmental exposure and disease development.Traditional tear analysis methods usually require a large amount of tear fluid,and require time-consuming and labor-intensive sample preparation,which greatly limits the analysis of human tears.The tear analysis methods using Schirmer paper combined with paper spray mass spectrometry(Schirmer PSMS)is considered to have broad application prospects,because of the unique advantages such as less tear consumption,conveniently non-invasive sampling,and fast analysis speed.However,there is still a lack of methodological study on the applications of Schirmer paper spray mass spectrometry analysis in environmental health monitoring and disease diagnosis.In this work,monitoring nicotine in human tears to reveal the exposure of tobacco smoke in ambient air is investigated.The new Schirmer PSMS method is systematically established to identify and quantify nicotine in human tears that was exposed to tobacco smoke,and to depict the kinetics of nicotine in human tears.Analytical performances,including sensitivity,reproducibility,recovery,and linear range were also investigated in this work.The results show that Schirmer PSMS can be used for rapid qualitative and quantitative determination of trace environmental exposures in human tears.Furthermore,Schirmer PSMS combined with multivariate statistics is further developed for screening of tear biomarkers of human eye diseases in this work.The storage property of tear samples in Schirmer paper was investigated,showing that Schirmer paper has good capacity for storaging tear metabolies for a long time.A total of 134 human tear samples with meibomian gland dysfunction,senile cataract,and allergic conjunctivitis,and healthy volunteers are investigated in this research.By combining with multivariate statistical analysis,a variety of potential biomarkers of tear diseases were proposed.The results show that the Schirmer PSMS analysis of human tears is expected to apply in diagnosing human eye diseases.Overall,this work further develops the noninvasive microsampling method and direct mass spectrometry methods with Schirmer paper for human tear analysis,and thus improved the ability of Schirmer PSMS for analyzing human tears and provided comprehensive information to gain insight into environmental exposures and eye disease.The results also provide new ideas for the development of ophthalmology,mass spectrometry,metabolomics,environmental health and other fields in the future.