Preparation And Application Of Molecularly Imprinted Electrochemical Sensors For Three Typical Tumor Markers

At present,the malignant tumor which is called ?the first killer? has been a threat to human,but it isn't an incurable disease.The advisory committee of the World Health Organization proposed that if they had been early diagnosed,a third of the cancers could have been cured as in 1981.Tumor markers can reflect existence and growth of tumors,so the early diagnosis and treatment of tumors have important clinical value.Meanwhile,they are also of vital significance to evaluate the recovery and recurrence risk of cancer patients.Molecularly imprinted polymers(MIPs)have many properties,such as good stability,excellent selectivity,acid,alkali and high temperature resistance,easy storage,reusability and so on.Electrochemical sensors possess such excellent advantages as high sensitivity,quick response,low cost,convenient operation and so on.Therefore,molecular imprinting technology and electrochemical sensing technique are combined to prepare imprinted electrochemical sensors of tumor markers.This research will have essential research significance.In this contribution,we completed highly sensitive and selective determination for ?-fetoprotein(AFP),human chorionic gonadotropin(hCG)and prostate specific antigen(PSA)by preparing molecularly imprinted electrochemical sensors.The main research contents and results of this paper are as follows:1 ?-fetoprotein(AFP)is specific tumor marker of primary liver cancer.In this paper,surface imprinting was applied to fabricate AFP imprinted electrochemical sensor.Firstly,chitosan,glutaraldehyde and AFP were modified onto the surface of the glassy carbon electrode through layer-by-layer.Then,acrylamide was used as functional monomers and N'N-methylene bisacrylamide as crosslinking agent,polymerization reaction was initiated in the presence of ammonium persulfate.Finally,after AFP was washed off the polymer film,AFP imprinted electrochemical sensor was made.Highly sensitive and selective determination for AFP was achieved by optimizing the conditions.The proposed electrochemical sensor for AFP showed wider linear range and lower detection limit compared with other methods for detecting AFP reported.The linear range was 8.0×10-4-10 ?g·mL-1 with the detection limit of 9.6×10-5 ?g·mL-1.At the same time,satisfactory results compared with referencing method were obtained for determination of AFP in real human serum samples.2 Human chorionic gonadotropin(hCG)has been regareded as a biomarker for Gestational Trophoblastic Diseases(GTDs)such as choriocarcinoma and hydatidiform mole.In addition,it is also relevant to some non-pregnancy related diseases.In this paper,a hCG imprinted electrochemical sensor was obtained through surface imprinting and electropolymerization.Multi-walled carbon nanotubes,chitosan and glutaraldehyde were drop-casting on the surface of the working electrode in turn,then hCG was chemically bonded to the modified electrode.On the one hand,their synergy and physical and chemical properties not only increased the amount of the fixed templates,but also improved the detection sensitivity.O n the other hand,the method that chemically bond the imprinted molecues could save templates,prevent templates from dissolving,and decrease gathering rate of templates.Finally,electropolymerization method was convenient operation and fast response.Meanwhile,the thickness of the membrane formed by electropolymerization was easy to control and the membrane was attached closely to the surface of the prepared electrode.Compared with other electrochemical methods determining for hCG,the sensor exhibited excellent linear range and low detection limit.The linear range were 5×10-4-0.2 ng·mL-1 and 0.2-250 ng·mL-1 respectively with the detection limit of 0.035 pg·mL-1.This method also possessed properties,such as good accuracy,sensitivity,stability,repeatability and low detection limit.The developed electrochemical sensor will find great promise for detection and analysis in clinical applications.3 Recently,prostate specific antigen(PSA)is recognized as the best screening method for diagnosis of prostate cancer.Meanwhile the amount of PSA is also associated with breast cancer.In this study,PSA imprinted electrochemical sensor was successfully prepared by taking advantage of molecular imprinting technology,electrochemical sensing technique and nanotechnology,which possessed excellent selectivity and high sensitivity for PSA determination.At first,graphene-gold nanoparticles compound,chitosan,glutaraldehyde and PSA were attached to the surface of the working electrode by layer-by-layer modification.Then a layer of polymeric membrane was presented.At last,after elution process,PSA imprinted electrochemical sensor was prepared.The addition of graphene-gold nanoparticles compound and chitosan could greatly improve the sensitivity,strongt hen the stability and reduce detection limit of the prepared sensor.The desighed sensor showed good linear range between 1.0×10-3-0.1 ng·mL-1 and 0.1-100 ng·mL-1 with the detection limit of 0.15 pg·mL-1.The results indicated that the proposed sensor was high sensitivity,better accuracy,satisfactory stability,good repeatability and so on.Thus,it has the potential to find application in clinical detection tumor markers with good developments and application.