The Study On Lesion Detection Methods Of Biological Tissue Based On Terahertz Time-domain Spectroscopy

Terahertz time-domain spectroscopy(THz-TDS),as a burgeoning detection technology,has bright prospect in food determination,drug testing,security inspection and so on.Over the last decade,it has drawn widespread attentions in biomedical research especially in the tumor detection academic circle with unique advantages like non-destructive,sensitive to water and biological molecules.Tumor lesions can be found in the pathological changes of tissue and the content or structural changes of the lesion markers.Therefore,the detection of lesion tissue and lesion markers is the two main methods of clinical tumor diagnosis.With the support of National Science Foundation,the research on both lesion tissue detection level and lesion marker molecular detection level is carried out with THz-TDS.The main contributions and innovations of this dissertation are as follows:(1)Human tissue is a kind of multicomponent mixture,there exists a experimental technical problem that it is hard to register a THz detection point and its accurate corresponding position in pathology image.To search for accurate detection approach,we use tissue microarray technology to process paraffin-embedded human gastric tissue,and then contrasts the THz absorption coefficient and refractive index spectrum of detection subjects which are divided as registered experimental group and unregistered control group.The result reveals that the detection accuracy brought by tissue microarray technology helps better discriminating tumor samples and normal samples.(2)To analyze and identify pathological tissue with TDS-TDS,we first analyzed the mechanism of the difference between gastric tubular adenocarcinoma and normal tissue in THz response with histopathological information brought by tissue microarray technology,which is focused on the difference of cell density,cell nucleus,and cell microenvironment.Based on the mechanism of the difference between tumor and normal tissue THz response,the discriminant model of gastric cancer tissue is proposed.Furthermore,some typical samples are predicted by the discriminant model.(3)The detection of lesion markers based on TDS-TDS is an important direction.The protein hydration layer can reflect the change of the actual molecular state of protein.In addition,the abnormal modification of protein methylation is related to tumor lesions.Between different protein,hydration characteristics change and conformation changes caused by structural modifications in the terahertz band response mechanism has a certain commonality,bovine serum albumin in the study of molecular biology has the advantage of easy access and good stability,often used as a model in the study of protein.With bovine serum albumin and methylation bovine serum albumin as model proteins,we verify the THz detection sensitivity of the protein surface hydration layer according to the non-linearity between the sample absorption coefficient and the protein concentration.Meanwhile,the difference of hydration layer between the two is analyzed according to the tendency.In addition,the sensitivity of terahertz absorption coefficient,refractive index and dielectric parameters to bovine serum albumin and its methylated object is compared using principal component analysis,by which we propose the discriminant model of protein methylation.The analysis result show that the combination of refractive index and dielectric dissipation factor for the study of protein methylation modification has better detectability.The results show the feasibility of terahertz spectroscopy in the detection of protein hydration layer and structural modification.To sum up,this dissertation takes the advantage of pathology registration at the level of biological tissue to strengthen the correlation between THz detection and actual pathology,and studies the detection ability of TDS-TDS on the hydration layer and structural modification of protein at the molecular level.The progress and achievements of this study have reference to the application of terahertz time domain spectroscopy in lesion detection.