Molecularly Imprinted Photo-electrochemical Sensors For Tumor Markers Based On Polymerized Ionic Liquid Hydrogel

Ionic liquids commonly consist of large organic cations and small inorganic anions.They possess many excellent characteristics such as thermal stability,non-volatile,good electrical conductivity,and biocompatibility.Through regulating cations and anions,ionic liquids with specific functions and properities can be designed.When ionic liquid is polymerized,the polymerized ionic liquids?PILs?not only maintains the inherent properties of ionic liquid,but also can help to increases the chemical stability and physical rigidity.In the field of molecularly imprinted sensors,PILs have aroused great attention.The imprinted hydrogel have been proved to possess good affinity and selectivity towards target molecules.Hydrogel is a network system with high water absorption and elastic matrix.It can absorb a large amount of water and maintain its three-dimensionalstructure.Hydrogelcansupplyabiocompatible microenvironment to maintain the biological activity and structure conformation of protein,thus improving the imprinted efficiency and the sensing performances of the molecularly imprinted sensors.Molecular imprinting technology is a relatively simple,low-cost and highly selective method for recognition of target molecules,and has been paid much more attention recently.Photoelectrochemical sensor is a newly developed analytical method based on photoelectric conversion characteristics of photoactive materials.It combines the excellent characteristics of optical analysis and electrochemical sensing,using light as the excitation signal to detect the electrochemical signal,and the detection signal?photocurrent?is completely separated from the excited signal?light?,so that the background signal is very low,and the sensitivity can be comparable to electrochemiluminescence.Moreover,the instrument of photoelectric sensor is simple,easy to miniaturization,and the equipment is also cheaper.Up to now,molecular imprinting combined with photoelectrochemical sensing technology has attracted more and more attention,but most applications are focused on the detection of small molecules.There are still some challenges in the molecular imprinting process of biomolecules,such as the denaturation of biomolecules by organic solvents,the harsh polymerization conditions leading to the deactivation of biomolecules and the irreversible conformation change,the difficulty to remove the target molecules from the polymer and to rebind to the imprinted sites and so on.A molecularly imprined process in aqueous solution with mild polymerization conditions is suitable for biomolecules.It enables the imprinted sensor to provide high sensitivity,selectivity and accuracy for the detection of biomolecules.Till now,molecularly imprinted photoelectrochemical sensors based on semiconductor nanomaterials have been paid more attention.However,the photoelectric conversion efficiency for the most of semiconductor nanomaterials is very low.Especially when biological macromolecules are introduced into the sensing system,the separation of charge-hole pairs will turn worse due to the poor conductivity and large size of biomolecules which can hamper the electron transfer rate and mass transfer.As a result,the photoelectrochemical response will decrease and thus limit the improving the performances of the developed sensors.Therefore,to explore photoactive materials with high carrier separation efficiency is of great importance for the photoelectrochemical sensing biomolecules.Based on the above mentioned,the contents of this dissertation are presented as following:1.Gold nanoparticles?AuNPs?were prepared with 1-vinyl-3-bromopropyl imidazolium bromide ionic liquid as functional monomer and chlorosulfic acid as precursor.Water-soluble near infrared ZnCdHgSe quantum dots were synthesized by using N-acetyl-L-cysteine as the functional reagent and stabilizer.Then,AuNPs/ZnCdHgSe nanocomposites were successfully prepared,and were used as photoactive element to fabricate a photoelectrochemical sensing platform.Human epididymal protein 4?HE4?,a tumor marker for early diagnosis of ovarian cancer,is used as the template molecule,and 3-{[{4-[(?amamyl?aminoethyl methacrylate]butyl methacrylate]methacrylate]methacrylate]propyl}-1-vinyl imidazole bromide ionic liquid?CCPEimBr?is used as the functional monomer to prepare a molecularly imprinted polymerized ionic liquid hydrogel film on the AuNPs/ZnCdHgSe modified glassy carbon electrode?GCE?.A molecularly imprinted photoelectrochemical sensor was obtained after removing the template.The sensor was demonstrated to possess high sensitivity and high selectivity towards human epididymal protein 4?HE4?.The photocurrent variation before and after rebinding HE4 shows a good linear relationship with the HE4 concentration in the range of 25 pg mL^-1-4 ng mL^-1.The detection limit is calculated to be 15.4 pg mL^-1?S/N=3?.The sensor was applied to determining HE4in human serum samples,and the results were well consistent with that of chemiluminescence analysis.The sensor shows excellent selectivity,sensitivity,stability and accuracy for HE4 determination.The developed molecularly imprinted photoelectrochemcial sensing platform possesses potential applications in other biomarkers just by substituting the template.2.Hollow gold nanoballs?HGNBs?were prepared by 1-benzyl-3-bromide bromide ionic liquid with chlorolylic acid as precursor,and N-methyl-2-pyrrolidone?NMP?was used as the solvent to prepare monolayer or a few layer MoSe₂ nanoscale thorough the exfoliation of MoSe₂ bulk crystal by ultrasonication.Based on the interaction between sulfur atoms exposed to the crystal surface and gold atom on HGNBs,HGNBs were integrated onto the surface of MoSe₂ nanosheets surface to prepare a HGNBs/MoSe2 nanocomposite.The HGNBs/MoSe2 composite can produce stable photocurrent when used as photoactive material to construct a sensing platform.Using the carcinoembryonic antigen?CEA?as a template,3-{[{4-N,N-double[?ammethyl?methacrylate]butyl methacrylate}??amyl?aminoethyl methacrylate?ethyl methacrylate]propyl}-1-vinyl imidazolium bromide ionic liquid?BCCPEimBr?as a functional monomer,a molecularly imprinted polymerized ionic liquid hydrogel film was prepared on a HGNBs/MoSe₂ modified glassy carbon electrode surface.After removing the templates,a molecularly imprinted photoelectrochemical sensor was achieved for determining CEA.The photocurrent variation before and after recognition of CEA shows a good linear relationship with the concentration of CEA in the range of50 pg mL^-1-5 ng mL^-1,and the detection limit is 11.2 pg mL^-1?S/N=3?.The sensor shows good selectivity,sensitivity and stability.The molecularly imprinted photoelectrochemical sensing platform can also be used for other biomolecules by substituting the template.