Development And Application Of Tumor Marker Detection Chip Integrated With Organic Electrochemical Transistor

Cancer is one of the major public safety concerns for human beings,and it has an immeasurable impact on people’s quality of life and safety.At present,there is no completely reliable treatment for most cancers in the human body.Conventional treatment methods not only have huge side effects,but also have different curative effects from person to person.It is difficult to further improve the survival rate of patients,but in the early stage,a higher cure rate can be achieved with the existing treatment methods.Therefore,compared with the development of new and more effective anti-cancer drugs,improving the screening methods for early cancers to achieve early detection and early treatment is also an effective way to treat cancer.In humans,the content of spermine（Spm）and its derivatives N¹,N¹²-diacetylspermine（Di Ac Spm,DAS）are related to cell proliferation,and have been extensively studied as a marker for early cancer and cancer treatment effect evaluation.In this paper,molecularly imprinted polymer modified organic electrochemical transistors and microfluidic technology are combined to develop two new types of microfluidic chip sensors,which realize the highly sensitive detection of tumor markers Spm and DAS in urine.The main contents are as follows:The extended gate field effect transistor（EG-FET）sensor extends the gate of the field effect transistor（FET）into a solution environment and forms an electrical circuit with the reference electrode,thereby significantly improving the detection sensitivity of the sensor.In this paper,firstly,the molecularly imprinted polymer（MIP）of Spm was successfully prepared by electropolymerization.Then a new electrochemical sensor for the detection of tumor marker Spm was constructed based on the Spm-MIP and EG-FET.Scanning electron microscopy（SEM）was used to characterize the surface combined with EG-FET morphology of Spm-MIP.The highly selective adsorption of Spm-MIP to Spm molecules was studied by cyclic voltammetry（CV）and differential pulse voltammetry（DPV）.Under the optimal experimental conditions,the EG-FET sensor realizes the highly sensitive detection of Spm in urine samples with a detection limit of 4.5×10^-11 M and a linear range of 10^-10～10^-6 M.This Spm sensor has the advantages of high sensitivity,good selectivity.Also it has the advantages of simple structure and economical cost.In this paper,DAS molecularly imprinted polymer（DAS-MIP）was prepared by electropolymerization,the OECT device with organic semiconductor PEDOT:PSS as the conductive channel and DAS-MIP as the modified gate was integrated.A"sandwich"configuration of the tumor marker DAS microfluidic chip sensor was developed.Scanning electron microscopy（SEM）was used to characterize the surface morphology of DAS-MIP,and the highly selective adsorption properties of DAS-MIP to DAS molecules were studied by cyclic voltammetry（CV）,and the preparation parameters were optimized.The OECT device in the microfluidic chip achieved a switch current ratio close to 100 and a transconductance of 0.075 m S in the performance test of the sensor.Under the optimal experimental conditions,the microfluidic chip sensor realizes the highly sensitive detection of DAS in urine samples with a detection limit of 1.4×10^-10 M and a linear range of10^-10～10^-4 M.The DAS-MIP modified grid is electrochemically polymerized on a self-made miniature three-electrode.This method simultaneously meets the requirements of a small amount of solvent consumption and bonding with chip.The DAS microfluidic chip sensor realizes the isolation of the detection platform and the external environment.Further more,it improves the detection sensitivity of the device and achieves low consumption of test samples.The DAS sensor has the advantages of high sensitivity,good selectivity and low sample consumption.It is economical and has the ability to work stably in a wide range of injection flow rates.The anti-interference test of the microfluidic chip sensor shows that coexisting substances such as uric acid,ascorbic acid,and glucose in body fluids have little effect on the sensor.