Research On Efficient Measurement Method Of Breath Isoprene Based On CRDS

Lung cancer is one of the most common malignant tumors worldwide.Currently,effective screening methods for early lung cancer are still scarce.Isoprene is a potential breath biomarker for lung cancer.Non-invasive breath analysis provides useful idea for early diagnosis of lung cancer.Cavity ringdown spectroscopy(CRDS)is a laser spectroscopy technology with high sensitivity for quantitative analysis.Compared with mass spectrometry,CRDS is portable and low cost.Compared with electrochemical sensors,CRDS has high sensitivity and high precision.CRDS has unique advantages for real time,accurate,and efficient measurement of breath biomarkers.These advantages make CRDS very suitable for real time and online measurement of human breath isoprene.Objective:To establish a CRDS measurement method for breath isoprene that can meet the requirements of clinical limit of detection(LoD).To build a CRDS-based breath isoprene analysis system and achieve high accuracy,high stability,high sensitivity analysis of human breath isoprene.To explore the feasibility of the two-molecule cooperative measurement method of CRDS preliminarily.And to promote the application of CRDS in non-invasive lung cancer diagnosis and and screening.Methods:First,the laser wavelength-226.56 nm is selected,and the interference analysis of the isoprene absorption spectrum is discussed.A dye laser pumped by a Qswitch Nd:YAG is utilized as the light source to generate the UV light.A CRDS-based breath isoprene analysis system is built,and the typical CRDS ringdown signal is linearly fitted.The absorption cross section at 223-227.4 nm is measured using isoprene standard gas.Evaluate system performance,including stability,detection limit,linear response,repeatability,time response,and accuracy.The influence of breath sample bags,water vapor,and background air on the experimental results are studied.Subsequently,the concentrations of breath isoprene in 74 patients with lung cancer,15 patients with benign lung lesions and 58 healthy volunteers are compared.The significance of breath isoprene in the diagnosis of lung cancer is evaluated.Finally,the feasibility of the CRDS-based two-molecule cooperative measurement method is tested.Results:1.We investigate spectral absorption interference and selected an optimal detection wavelength at 226.56 nm with minimum to no spectral interference.2.The fitting result of typical ringdown waveform of CRDS-based breath isoprene analysis system recorded under vacuum shows good linearity(R2=0.99).The ringdown time under vacuum is 0.88624 μs with stability of 0.2%,which leads to mirror reflectivity of 99.81%and LoD of 0.47 ppbv.The CRDS system shows good linear response(R2=0.99),and high accuracy(R2=0.906).3.The decreasing trend of absorption cross-section of isoprene at 223-227.4 nm is also in a good agreement with those reported.The absorption cross-section at 226.56 nm is(1.93±0.0173)× 10-17 cm2/molecule.4.FEP bag has better stability over time.Water vapor has no effect on results.The air outside the laboratory is selected as the background air.5.Breath isoprene concentration is significantly higher in healthy individuals(274.1±130.4 ppbv)than in patients with lung cancer(114.9±38.4 ppbv)and benign lung lesions(128.9±43.2 ppbv).Breath isoprene concentrations of the three groups of subjects are not affected by gender,age,and BMI.ROC curve result proves that the concentration of breath isoprene is meaningful for the diagnosis of lung cancer(AUC=0.915,sensitivity 82.8%,specificity 89.2%,P<0.01).6.The absolute value of the relative error of NO measured by the CRDS-based two-molecule cooperative measurement method is 0.2-7.2%,and the absolute value of the relative error of isoprene is 0-9.2%.Conclusion:The CRDS measurement method of breath isoprene is a reliable method with high accuracy,high stability and high sensitivity for human breath isoprene,which can achieve non-invasive detection of breath from lung cancer patients and healthy people,and further provide a basis for early diagnosis and disease screening of lung cancer.