Detection Of Bladder Transitional Epithelial Carcinoma Based On Microfluidic Chip

Background: Bladder cancer is one of the top ten malignancies,about 95 % of which is bladder transitional cell carcinoma.Transitional epithelial cancer cells of the bladder will be shed into the urine,and the content of protein biomarks of bladder cancer in the urine will also be increased significantly,which provide feasible diagnostic indexes for cancer detection.Clinical detection methods of bladder cancer include routine urine examination,cystoscopy,cytology,venous urography and fluorescence in situ hybridization(FISH)technique,and so on.However,these methods have some shortcomings such as invasive,high false positive rate,susceptible to interference and expensive cost.Up to now,there has no clinically noninvasive detecting methods with high sensitivity and specificity as well as low cost.Materials and methods: A new microfluidic chip is designed for the detection of bladder transitional epithelial carcinoma.The COMSOL Multiphysics software is used to simulate and optimize the structure of the microfluidic chip to get the micropillar array with better fluid field;The inner surface of the chip is modified by silanization to fix specific antibody,and the optimal pre-treatment condition is confirmed;Based on the micropillar array and principle of antigen antibody immune adsorption,cancer cells as well as biomarkers nuclear matrix protein22(NMP22),bladder tumor antigen(BTA)and fibrin degradation products(FDP)in urine samples are detected with the chip to diagnose bladder transitional epithelial carcinoma,and the detection performance of chip is improved by joint detection;The precision and timeliness of the chip are investigated by using diluted urine samples and the prepared chip cryopreserved in a long time.Results: The rectangular array has better simulation result and is used in chip design and fabrication;When the silanization time is 30 min,the immobilization effect of the specific antibody in the chip is better;The chip can detect significant content difference of bladder cancer cell and protein biomarkers between patients and volunteers' urine samples;Through conjoint detection of multiple indexes,the sensitivity and the specificity of the microfluidic chip are improved;In addition,the chip is used to detect the urine samples of the patients diluted to 2/3,and the significant difference between the urine samples and the control groups is found,which indicates that the chip has good precision;Finally,the detection performance of the chip preserved at-20 ? in 180 days don't present significant change,and it illustrates the chip has good timeliness.Conclusion: this study designed a new noninvasive microfluidic chip for the detection of bladder transitional epithelial carcinoma.By capturing and detection of bladder transitional epithelial carcinoma cells as well as protein biomarkers NMP22,BTA and FDP,bladder transitional epithelial carcinoma is diagnosed successfully based on the chip.If the threshold of prediction probability is obtained and set to 67.18 % based on the largest Youden index,the sensitivity and specificity of conjoint detection can reach up to 85.7% and 100%,respectively.The microfluidic chip designed in this study provides a powerful tool for clinical diagnosis.It has the potential of early detection and a certain application prospect in market promotion.