Fabrication Of Photonic Crystals And Their Application In Early Diagnosis Of Cancer

Cancer is one of the most severe diseases in the world,and the cure rate can be significantly increased for early-stage cancer patients.Therefore,early diagnosis of cancer is of great significance.The research on cancer biomarkers and characteristics of tumor microenvironment is an effective method for screening of early-stage cancers.Generally,conventional clinical cancer diagnosis methods,such as blood testing,imageological diagnosis and genetic screening,not only consume a lot of resources and time,but the accuracy,sensitivity,and specificity of detection still require to be improved,which cannot meet the needs of early cancer screening.Therefore,it is particularly important to develop high-sensitivity,high-accuracy,efficient and simple early cancer diagnosis methods.Photonic crystals are optical structures formed by dielectric materials with different refractive indices arranged periodically in space.The structures have great potential application in the fields of biochemical sensing,metamaterials,and information storage.Biomedical optical detection based on photonic crystal materials is one of the important research topics in the field of biomedical engineering.However,the photonic crystal structure-based biosensor device lacks efficient system integration and cannot perform real-time in situ analysis of tumor biomarkers in body fluid,which limits its application in clinical diagnosis.To solve these problems,we prepared photonic crystal carriers with different structures and used them for the highly sensitive detection of biomarkers in vitro and in vivo,further expanding the application of photonic crystals in cancer diagnosis.The main research contents are as follows:(1)A microfluidic Slip Chip integrated with photonic crystal membrane was constructed for efficient separation and sensitive detection of extracellular vesicles.First,the double-layer nano-filtration membrane is applied to achieve high-efficiency separation and enrichment of extracellular vesicles,which are biomarkers of early cancer.Then,through the specific binding of extracellular vesicle surface proteins and aptamers,the high-sensitivity detection of extracellular vesicles is realized by the fluorescence enhancement effect of the photonic crystal structure.Finally,the microfluidic Slip Chip was used to accurately analyze extracellular vesicles in clinical samples and successfully distinguished healthy and cancerous subjects.This work provides a new idea for constructing an integrated,portable,and highly sensitive early cancer screening system.(2)The construction of nitrocellulose microneedles with photonic crystal structure on the surface is applied for the high-sensitivity detection of biomarkers in tumor interstitial fluid.The microneedles with photonic crystal structure on the surface were prepared by the micromolding method.The fluorescence enhancement effect of the photonic crystal and the excellent protein adsorption capacity of the nitrocellulose material were utilized.The immunosandwich fluorescence method was used to realize the quantitative analysis of the biomarkers on the microneedles.In practical applications,the photonic crystal microneedle is applicable to achieve efficient capture and detection of targeted tumor biomarkers in tumor interstitial fluid of tumor-bearing mice.This work provides a new strategy for minimally invasive continuous and efficient monitoring of targeted biomarkers in tumor interstitial fluid with tumor growth.(3)The p H-responsive photonic crystal hydrogel microspheres were constructed for long-term continuous monitoring of tumor microenvironment and controlled drug release.The changes in the acidity of the tumor microenvironment reflect the growth of the tumor,so long-term continuous monitoring of the tumor microenvironment p H is essential.The p H-responsive photonic crystal hydrogel microspheres were prepared by the template method.When the environmental p H changes,the micro-nano structure and reflection peak of the hydrogel microspheres change accordingly,which can response to the changes in the tumor microenvironment quickly and accurately.Since the hydrogel biomaterials used have good biocompatibility,the prepared hydrogel microspheres were injected into the tumor site of tumor-bearing mice to achieve long-term continuous monitoring of the tumor microenvironment p H.In addition,the ordered porous structure of the photonic crystal hydrogel microspheres realizes the high-efficiency load of the anti-tumor drug doxorubicin.While continuously monitoring the tumor microenvironment,controlled release of the loaded drug can be also achieved based on the p H response of hydrogel microspheres,thus fulfilling concurrent tumor diagnosis and treatment.