Improvement Of Silicon Nanosensor And Detection Of Tumor Markers And Prognosis-related Proteins

Malignant tumors are still the main cause of death in humans.Early diagnosis and treatment of tumors largely determine the prognosis of the tumor.Among the existing tumor screening and examination methods,the detection of tumor marker proteins is still a convenient and quick means of examination.However,current detection methods have problems such as complicated steps,low sensitivity,and risk of radioactive contamination.With the development of nanoscience and nanotechnology,the development of biomedical technology has been promoted.Nanowires are highly functional structures in a variety of nanomaterial structures,providing unique properties due to their one-dimensional structure.The nanowire-based sensor has the advantages of small volume,real-time response,high sensitivity,specificity,and portability,and is of great significance for rapid and high-sensitivity detection of tumor markers.This paper focused on the preparation of silicon nanowires filed effect transistor(Si NWs-FET)biosensors,the improvement of device power performance,surface functionalization,and the detection of tumor markers in human serum.We developed a new class of nanoscale biosensors which were highly sensitive,highly specific,stable,and reusable.It could detect tumor markers in a serum with rapid,high sensitivity and high specificity.(1)Silicon nanowire field effect transistor biosensor applied to the detection of tumor markers.This study used a “top-down” method to prepare a Si NWs-FET biosensor.The natural oxide layer was modified with 3-aminopropyl-triethoxysilane(APTES),and then the tumor marker monoclonal antibody was immobilized on silicon nanoparticle by covalent modification with glutaraldehyde(Glu).The surface of the wire was finally sealed with a polydimethylsiloxane(PDMS)microchannel.Different concentrations of tumor marker standard solution were pumped into the sensing area through the microchannel.We observed a curve of current changes caused by the combination of tumor markers and antibodies on the surface of the silicon nanowire biosensor.The results confirmed that the Si NWs-FET biosensor developed by this study could be used to detect low concentrations of tumor markers.(2)Improvement of silicon nanowire field effect transistor biosensorA double-gate Si NWs-FET biosensor was prepared by adding a top gate voltage to the Si NWs-FET biosensor.When the tumor marker standard was detected,the surface gate voltage and the drain voltage were reduced compared with the single-gate mode sensor,and the source-drain current Ids was significantly increased in the output transfer curve,thereby improving the regulation capability and stability of the device.Limited to the effect of Debye screening effect in serum,it was difficult to realize real-time detection of target proteins in serum by silicon nanowire biosensors.Lowering the serum salt ion concentration can effectively reduce the detection interference of the Debye shielding effect.In this study,for the first time the original serum was desalted using a self-made dialyzer.It was found that the serum subjected to dialysis and desalting could change the current of the biosensor,and the original serum without any treatment did not cause the response of the biosensor,and the higher the tumor marker concentration,the more obvious the increase of the current.The results demonstrated that the double-gate-regulated silicon nanowire biosensor combined with the dialysis system successfully had overcome the influence of the Debye screening effect and realized the detection of tumor markers in the original serum.Due to the strong affinity between the antigen and the antibody,it was difficult to remove the antigen-antibody complex from the surface of the NW-FET at the end of the assay,so the biosensor we prepared previously could only be used for a single measurement.Based on the previous devices,we made the MPTMS/Si NWs-FET sensor and removed the antibody-target molecule complex by reversible disulfide bond function for reuse.It was found that the cleaned MPTMS/Si NWs-FET showed a significant drop in current,and the CEA standard was again tested,and the current again showed a significant increase.This proved that the reversible disulfide bond modification of the surface of the device could achieve the purpose of repeatable detection.(3)Studies have shown that tumor metastasis may be related to tumor cell epithelial-mesenchymal transition process.This study explored the use of improved biosensors for the detection of breast cancer cell mesenchymal markers N-cadherin.Further tests were underway,and markers such as N-cadherin were expected to be specific markers for identifying circulating tumor cells.We hope to successfully perform circulating tumor cell detection using our newly developed biosensor.Through the improvement of device fabrication and modification methods,the stability,sensitivity,controllability and repeatability of Si NWs-FET sensors was further improved,and the detection bottleneck has been successfully broken.Real-time detection of tumor marker proteins in serum was achieved using an innovative dialyzer.